WorldWideScience

Sample records for adjusted-dose oral warfarin

  1. Topical Antimycotics for Oral Candidiasis in Warfarin Users

    DEFF Research Database (Denmark)

    Hellfritzsch, Maja; Pottegård, Anton; Pedersen, Andreas James Thestrup

    2017-01-01

    Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study...... for oral candidiasis....... with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical...

  2. Topical Antimycotics for Oral Candidiasis in Warfarin Users.

    Science.gov (United States)

    Hellfritzsch, Maja; Pottegård, Anton; Pedersen, Andreas James Thestrup; Burghle, Alaa; Mouaanaki, Fatima; Hallas, Jesper; Grove, Erik Lerkevang; Damkier, Per

    2017-04-01

    Treatment for oral candidiasis in warfarin users may be complicated by drug-drug interactions (DDIs) between warfarin and topically applied antimycotics. However, current knowledge of these putative DDIs is merely based on case series. We therefore performed a cohort cross-over study with the objective to evaluate the potential DDIs between warfarin and miconazole oral gel or nystatin oral solution. The cohort consisted of individuals using warfarin in the period of 1998-2012 (n ≈ 7400). We collected data on cohort members' measurements of the international normalized ratio (INR) from a clinical database, and obtained information on their use of topically applied miconazole and nystatin from a regional prescription register. Potential DDIs were assessed by comparing INR values before and after initiation of an antimycotic drug. Among 17 warfarin users exposed to miconazole oral gel, the mean INR increased from 2.5 (95% CI: 2.1-2.8) to 3.8 (95% CI: 2.8-4.8) after exposure, corresponding to a mean INR increase of 1.4 (95% CI: 0.3-2.4). Among 30 warfarin users exposed to nystatin oral solution, the mean INR was 2.7 (95% CI: 2.3-3.1) before and 2.5 (95% CI: 2.2-2.9) after exposure. In conclusion, we found evidence supporting a clinically relevant drug-drug interaction between warfarin and miconazole oral gel. In contrast, we did not find any indication of an interaction between warfarin and nystatin oral solution. Nystatin rather than miconazole should be preferred when treating warfarin users for oral candidiasis. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  3. Oral warfarin intake affects skin inflammatory cytokine responses in rats.

    Science.gov (United States)

    Aleksandrov, Aleksandra Popov; Mirkov, Ivana; Zolotarevski, Lidija; Ninkov, Marina; Mileusnic, Dina; Kataranovski, Dragan; Kataranovski, Milena

    2017-09-01

    Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Interaktion mellem warfarin og oral miconazol-gel

    DEFF Research Database (Denmark)

    Ogard, C G; Vestergaard, Henrik

    2000-01-01

    We report a case of a 76 year-old woman who had been taking warfarin for seven years because of relapsing deep venous thrombosis. Her daily maintenance dose was 5 mg. Monthly measurements of international normalised ratio (INR) were stable between 2-3. She developed oral candidiasis and miconazole...

  5. Warfarin

    Science.gov (United States)

    ... of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have suffered a heart attack. ... should not take warfarin unless they have a mechanical heart valve. Talk to your doctor about the use of ...

  6. Comparing Direct Oral Anticoagulants and Warfarin for Atrial Fibrillation, Venous Thromboembolism, and Mechanical Heart Valves.

    Science.gov (United States)

    Marcy, Todd R; Truong, Teresa; Rai, Andrea

    2015-11-01

    To summarize available data for use of direct oral anticoagulants in nonvalvular atrial fibrillation, venous thromboembolism, and mechanical heart valves including dose-response consistency to offer considerations for pharmacotherapeutic decision-making for oral anticoagulants. A Medline search of English-language studies published between 2000 and March 2015 was conducted to identify pertinent papers using combinations of the following words: apixaban, atrial fibrillation, dabigatran, direct oral anticoagulant, edoxaban, factor IIa inhibitors, factor Xa inhibitors, mechanical heart valves, novel oral anticoagulant, rivaroxaban, venous thromboembolism, and warfarin. Original studies, guidelines, and approved prescribing information were evaluated and included if contributing new or complementary data toward the objective. References for all identified studies were reviewed and entries included if contributory. Randomized controlled trials have established the safety and efficacy of direct oral anticoagulants in atrial fibrillation and venous thromboembolism for most patient groups. Direct oral anticoagulants should not be used in patients with mechanical heart valves until proven safe and effective. There are groups for which questions remain regarding inter-patient dose-response consistency for direct oral anticoagulants. There are postmarketing data suggesting poorer real-world performance of dabigatran relative to clinical trial data. Direct oral anticoagulants offer several advantages over warfarin, and large clinical trial data establish the appropriateness of their use in broad populations. There remain groups for whom the relative benefit and risk of these agents relative to warfarin are uncertain. A patient-specific approach in pharmacotherapeutic decision-making is appropriate.

  7. Comparative safety of direct oral anticoagulants and warfarin in venous thromboembolism: multicentre, population based, observational study

    Science.gov (United States)

    Jun, Min; Lix, Lisa M; Durand, Madeleine; Dahl, Matt; Paterson, J Michael; Dormuth, Colin R; Ernst, Pierre; Yao, Shenzhen; Renoux, Christel; Tamim, Hala; Wu, Cynthia; Mahmud, Salaheddin M

    2017-01-01

    Objective To determine the safety of direct oral anticoagulant (DOAC) use compared with warfarin use for the treatment of venous thromboembolism. Design Retrospective matched cohort study conducted between 1 January 2009 and 31 March 2016. Setting Community based, using healthcare data from six jurisdictions in Canada and the United States. Participants 59 525 adults (12 489 DOAC users; 47 036 warfarin users) with a new diagnosis of venous thromboembolism and a prescription for a DOAC or warfarin within 30 days of diagnosis. Main outcome measures Outcomes included hospital admission or emergency department visit for major bleeding and all cause mortality within 90 days after starting treatment. Propensity score matching and shared frailty models were used to estimate adjusted hazard ratios of the outcomes comparing DOACs with warfarin. Analyses were conducted independently at each site, with meta-analytical methods used to estimate pooled hazard ratios across sites. Results Of the 59 525 participants, 1967 (3.3%) had a major bleed and 1029 (1.7%) died over a mean follow-up of 85.2 days. The risk of major bleeding was similar for DOAC compared with warfarin use (pooled hazard ratio 0.92, 95% confidence interval 0.82 to 1.03), with the overall direction of the association favouring DOAC use. No difference was found in the risk of death (pooled hazard ratio 0.99, 0.84 to 1.16) for DOACs compared with warfarin use. There was no evidence of heterogeneity across centres, between patients with and without chronic kidney disease, across age groups, or between male and female patients. Conclusions In this analysis of adults with incident venous thromboembolism, treatment with DOACs, compared with warfarin, was not associated with an increased risk of major bleeding or all cause mortality in the first 90 days of treatment. Trial registration Clinical trials NCT02833987. PMID:29042362

  8. WARFARIN AND ITS IMPORTANCE IN THE ERA OF NEW ORAL ANTICOAGULANTS. ISSUES OF MONITORING THE EFFECTIVENESS AND SAFETY OF TREATMENT

    Directory of Open Access Journals (Sweden)

    S. Yu. Martsevich

    2017-01-01

    Full Text Available Oral anticoagulant (OAC therapy is currently gaining special importance due to the significant spread of atrial fibrillation (AF in the population (especially in older age groups. The use of OAC in AF has an extensive evidence base, which confirms a significant decrease in the number of strokes and total mortality in the context of anticoagulation therapy (ACT in AF. Currently, the "gold standard" of the OAC is warfarin, which has proved effectiveness in all categories of patients with AF. A whole group  of new OAC (NOAC also appeared. In Russia, dabigatran, rivaroxaban and apixaban have been registered. All NOAC were studied in randomized clinical trials (RCTs in comparison with warfarin, mainly in patients with non-valvular AF, therefore, in valvular AF, as well as in patients with severe renal failure, warfarin remains the drug of choice. Advantages of warfarin in comparison with NOAC are the presence of known  antidote and standardized indicator of the efficacy and safety of the anticoagulation therapy – International Normalized Ratio (INR, as well as low price of the drug. The leading problem in the treatment of warfarin is the complexity and, at the same time, a strong  need to maintain INR within the therapeutic "window" of at least 60% of the treatment time. Obviously, the optimal solution to this problem is the possibility of self-testing of this indicator by the patient himself and,  probably, the ability to adjust the dosage of warfarin independently, to achieve the necessary values of INR (self-management or titrate the dose with the help of a medical consultation by phone (self-monitoring. To date, several devices have been developed for self-monitoring of anticoagulation therapy – coagulometers. Their use leads to a decrease in the number of thromboembolic complications, and from the results of some RCTs – to a decrease in the number of large bleedings and total mortality, and to improve the quality of life of AF patients

  9. Efficacy and Safety of Direct Oral Anticoagulants Compared to Warfarin in Prevention of Thromboembolic Events Among Elderly Patients with Atrial Fibrillation.

    Science.gov (United States)

    Kailas, Shilpa D; Thambuluru, Sirisha Reddy

    2016-10-18

    Direct oral anticoagulants (DOACs), previously also known as novel oral anticoagulants (NOACs), have increased the therapeutic options for stroke prevention in atrial fibrillation (AF). Previous studies comparing their relative efficacy and safety do not address age-related differences, such as comorbidities and physical and social boundaries. This review aimed to summarize and compare the clinical and safety outcomes of DOACs and warfarin for stroke prevention in AF in the elderly population (≥ 65 years). We searched PubMed for randomized controlled trials and meta-analyses that compared DOACs and warfarin in elderly patients with AF. Stroke and systemic embolism (SSE) and major bleeding (MB) were primary outcomes. Secondary outcomes included ischemic stroke, all-cause mortality, intracranial bleeding, and gastrointestinal bleeding. Of 66 studies identified, one randomized control trial (RCT) and one meta-analysis were included. DOACs were at least as effective at reducing the risk of SSE as warfarin. DOACs demonstrated a minimal benefit for ischemic stroke (dabigatran, 110 mg, relative risk (RR) 1.08; edoxaban, 60 mg, RR 1.00; and apixaban, 5 mg, RR 0.99). DOACs associated with decreased risk of MB relative to warfarin include dabigatran, 110 mg; apixaban, 5 mg; and edoxaban, 60 mg (RR 0.80, 0.70, and 0.80, respectively), while dabigatran, 150 mg, and rivaroxaban, 20 mg, increased risk (RR 0.79 - 0.83, respectively). Dabigatran, 110 mg and 150 mg doses, and edoxaban increased the risk of gastrointestinal bleeding (RR 1.04, 1.12, and 1.23, respectively). Lower rates of SSE and intracranial bleeding were seen with DOACs compared to warfarin. Dabigatran, 150 mg, and rivaroxaban, 20 mg, were associated with higher MB in older elderly compared to warfarin. DOACs may be attractive alternatives to warfarin, but further studies are needed to make clinical recommendations.

  10. Left Atrial Appendage Occlusion Device and Novel Oral Anticoagulants Versus Warfarin for Stroke Prevention in Nonvalvular Atrial Fibrillation: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

    Science.gov (United States)

    Briceno, David F; Villablanca, Pedro; Cyrille, Nicole; Massera, Daniele; Bader, Eric; Manheimer, Eric; Aagaard, Philip; Ferrick, Kevin; Gross, Jay; Kim, Soo Gyum; Krumerman, Andrew; Palma, Eugen; Guttenplan, Nils; Romero, Jorge; Fisher, John; Garcia, Mario; Natale, Andrea; Di Biase, Luigi

    2015-10-01

    Nonvalvular atrial fibrillation is the most common arrhythmia. Patients with nonvalvular atrial fibrillation are at increased risk of stroke; therefore, we evaluated the efficacy and safety of different approaches to prevent this major complication. We conducted electronic database searches of phase III randomized controlled trials. The groups were novel oral anticoagulants, Watchman left atrial appendage occlusion device (DEVICE), and warfarin. Efficacy outcomes were stroke or systemic embolism, and all-cause mortality. Safety outcome was major bleeding and procedure-related complications. A subgroup analysis of the elderly population was done. We used random-effects model to compare pooled outcomes and tested for heterogeneity. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed for each outcome. Seven randomized controlled trials (n=73,978) were included. There was a significant difference favoring novel oral anticoagulants for systemic embolism (OR, 0.84; 95% CI, 0.72-0.97; P=0.01), all-cause mortality (OR, 0.89; 95% CI, 0.84-0.94; P<0.001), and safety outcomes (OR, 0.79; 95% CI, 0.65-0.97; P=0.026) compared with warfarin. No difference was seen between DEVICE and warfarin for efficacy end points; however, DEVICE had more complications (OR, 1.85; 95% CI, 1.14-3.01; P=0.012). In the elderly (6 randomized controlled trials, n=30,699), systemic embolism was favored with novel oral anticoagulants over warfarin (OR, 0.77; 95% CI, 0.68-0.87; P≤0.001). No evidence of significant publication bias was found. Novel oral anticoagulants is superior to warfarin for stroke prevention in nonvalvular atrial fibrillation. This benefit was also observed in the elderly population. DEVICE is a reasonable noninferior alternative to warfarin for stroke prevention, but cautious use is essential given safety concerns. © 2015 American Heart Association, Inc.

  11. Safety and efficacy of direct oral anticoagulants compared to warfarin for extended treatment of venous thromboembolism -a systematic review and meta-analysis

    DEFF Research Database (Denmark)

    Sindet-Pedersen, Caroline; Pallisgaard, Jannik Langtved; Olesen, Jonas Bjerring

    2015-01-01

    OBJECTIVE: To examine and compare the safety and efficacy of extended treatment with dabigatran, apixaban, rivaroxaban and warfarin in patients with unprovoked venous thromboembolism. METHODS: PubMed and Embase were searched for randomized clinical trials reporting on the use of direct oral antic...

  12. Non-vitamin K oral anticoagulants are non-inferior for stroke prevention but cause fewer major bleedings than well-managed warfarin: A retrospective register study.

    Directory of Open Access Journals (Sweden)

    Vilhelm Sjögren

    Full Text Available For patients with atrial fibrillation, non-vitamin K oral anticoagulants, or NOACs (dabigatran, rivaroxaban, edoxaban, and apixaban have been proven non-inferior or superior to warfarin in preventing stroke and systemic embolism, and in risk of haemorrhage. In the pivotal NOAC studies, quality of warfarin treatment was poor with mean time in therapeutic range (TTR 55-65%, compared with ≥70% in Swedish clinical practice.We compared NOACs (as a group to warfarin in non-valvular atrial fibrillation, studying all 12,694 patients starting NOAC treatment within the Swedish clinical register and dosing system Auricula, from July 1, 2011 to December 31, 2014, and matching them to 36,317 patients starting warfarin using propensity scoring. Endpoints were thromboembolic events and major bleedings that were fatal or required hospital care. Outcome data were collected from validated Swedish hospital administrative and clinical registers.Mean age was 72.2 vs 72.3 years, proportion of males 58.2% vs 57.0%, and mean follow-up time 299 vs 283 days for NOACs and warfarin. Distribution of NOACs was: dabigatran 40.3%, rivaroxaban 31.2%, and apixaban 28.5%. Mean TTR was 70%. There were no significant differences in rates of thromboembolic/thrombotic events or gastrointestinal bleeding. NOAC treated patients had lower rates of major bleeding overall, hazard ratio 0.78 (95% confidence interval 0.67-0.92, intracranial bleeding 0.59 (0.40-0.87, haemorrhagic stroke 0.49 (0.28-0.86, and other major bleeding 0.71 (0.57-0.89.For patients with atrial fibrillation, NOACs are as effective for stroke prevention as well-managed warfarin but cause fewer major bleedings.

  13. The IL--6 dependent effect of oral warfarin in heart valve replacement patients by measuring interacting clinical and demographic variables

    International Nuclear Information System (INIS)

    Shafiq, H.; Rashid, A.; Majeed, A.; Razah, S.; Asghar, I.

    2016-01-01

    Objective: To examine an inflammatory effect of warfarin and comparing with IL-6 levels along with different demographic and clinical variables. Study Design: Quasi experimental study. Place and Duration of Study: Center of Research in Experimental and Applied Medicine (CREAM), Army Medical College/National University of Sciences and Technology, Islamabad from Oct 2013 to Oct 2015. Material and Methods: The study design was Quasi Experimental study. Samples were collected by Non probability convenience sampling. Total 76 patients were included according to warfarin dose response in warfarin therapy patients, i.e. 32(42 percent) were taking <5mg/day, 37(49 percent) had been put on dose 5-10mg/day and 7(09 percent) were taking>10mg/day of warfarin dose. Patient's demographic and clinical variables were noted i.e. age, gender, BMI, duration of therapy, INR history, hepatic, gastrointestinal and diabetic complications. Human IL-6 ELISA assay was performed. Results: The statistically significant difference was found between age groups (in years) and different levels of warfarin dose (p=0.046) along with IL-6 production. There is a negative correlation between warfarin dose and age group i.e. as age increases, the dose of warfarin decreases. Among the inter and intra-patient variability age and serum IL-6 levels were found to be statistically significant with warfarin dose response. BMI and warfarin dose were found to be weak positively correlated. Conclusion: A marked immunomodulatory response of warfarin was noted by measuring IL-6 levels. IL-6 levels retained a significant association with warfarin dose. (author)

  14. Hospital length of stay in patients initiated on direct oral anticoagulants versus warfarin for venous thromboembolism: a real-world single-center study.

    Science.gov (United States)

    Badreldin, Hisham

    2018-04-06

    This study was conducted to describe the real-world hospital length of stay in patients treated with all of the U.S. Food and Drug Administration approved direct oral anticoagulants (DOACs) versus warfarin for new-onset venous thromboembolism (VTE) at a large, tertiary, academic medical center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 441 patients included, 261 (57%) patients received DOACs versus 180 (41%) patients received warfarin. In the DOAC group, a total of 92 (35%) patients received rivaroxaban, followed by 83 (32%) patients received apixaban, 50 (19%) patients received dabigatran, and 36 (14%) patients received edoxaban. Patients initiated on DOACs had a statistically significant shorter hospital length of stay compared to patients initiated on warfarin (median 3 days, [IQR 0-5] vs. 8 days [IQR 5-11], P < 0.05). Despite the shorter hospital length of stay in patients receiving DOACs, the overall reported differences between the DOACs group and the warfarin group in terms of recurrent VTE, major bleeding, intracranial bleeding, and gastrointestinal bleeding at 3 and 6 months were deemed to be statistically insignificant.

  15. Renal function and risk of stroke and bleeding in patients undergoing catheter ablation for atrial fibrillation: Comparison between uninterrupted direct oral anticoagulants and warfarin administration.

    Science.gov (United States)

    Yanagisawa, Satoshi; Inden, Yasuya; Fujii, Aya; Ando, Monami; Funabiki, Junya; Murase, Yosuke; Takenaka, Masaki; Otake, Noriaki; Ikai, Yoshihiro; Sakamoto, Yusuke; Shibata, Rei; Murohara, Toyoaki

    2018-03-01

    The effect of uninterrupted oral anticoagulant use in patients with chronic kidney disease (CKD) during catheter ablation for atrial fibrillation (AF) is not fully understood. The present study aimed to evaluate the safety and efficacy of periprocedural uninterrupted direct oral anticoagulant (DOAC) use compared with those of uninterrupted warfarin use in patients undergoing catheter ablation for AF stratified by various renal function groups. A total of 2091 patients were retrospectively included in this study. The study population was divided into 4 groups: creatinine clearance level ≥80 mL/min (n = 1086), 50-79 mL/min (n = 774), 15-49 mL/min (n = 209), and <15 mL/min (n = 22). We investigated periprocedural complications and compared them between uninterrupted DOAC and warfarin groups. There was no significant difference in thromboembolic events among the 4 groups (0.6%, 0.6%, 1.0%, and 0%, respectively; P = .792). However, major bleeding events (0.9%, 1.4%, 4.8%, and 4.5%; P < .001) and minor bleeding events (4.1%, 6.1%, 11.5%, and 13.6%; P < .001) primarily occurred in patients with CKD. The rate of periprocedural complications in the DOAC group was similar to that in the warfarin group for each renal function category. Adverse events did not differ after adjustment using propensity score-matched analysis. Multivariate analysis showed that lower body weight, antiplatelet drug use, initial ablation session, and CKD were independent predictors of adverse events. The periprocedural bleeding risk was increased in patients with CKD. Uninterrupted DOAC and warfarin administration during catheter ablation for AF in patients with CKD is feasible and effective. Copyright © 2017 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  16. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack

    DEFF Research Database (Denmark)

    Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R

    2012-01-01

    In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients ...

  17. Administración oral de preparado parenteral de vitamina K en anticoagulación excesiva por warfarina Oral administration of intravenous preparation of Vitamin K for excessive anticoagulation due to warfarin

    Directory of Open Access Journals (Sweden)

    Yoleima Lozada

    2012-04-01

    Full Text Available La warfarina es frecuentemente usada en la terapia anticoagulante actual, su acción debe ser monitorizada usando el tiempo de protrombina expresado como International Normalized Ratio (INR; cuando se excede el rango de seguridad se puede administrar vitamina K (Vit-K, preferentemente por vía oral. Dicha presentación no está disponible en Venezuela. Se realizó un ensayo clínico, doble ciego, donde a 20 pacientes, edad 18-60 años, sin sangrado e INR inicial de 6 a 10 inclusive; les fue suspendida la warfarina e inmediatamente agrupados al azar a recibir dosis única de Vit-K (oral 1.25mg de Vit-K fraccionada de una presentación parenteral o placebo. El punto final primario, INR Anticoagulation therapy with warfarin, a common clinical practice, needs to be monitored using protombine time expressed as the International Normalized Ratio (INR; when safety range is exceeded, Vitamin K (Vit-K could be administered with preference orally. In Venezuela the specific oral preparation for Vit-K is not available. This is a double blinded, randomized, placebo controlled, clinical trial; 20 patients, age 18-60 year with initial INR ≥ 6, ≤10, were randomized to oral Vit-K 1.25mg (prepared from intravenous presentation or placebo plus withholding warfarin. INR < 3.5 at 24 hours of treatment (the primary end point was achieved by 70% among Vit-K, and 20% among placebo patients; given an absolute risk reduction (ARR, of 50% (CI95%: 14.4-85.6 ρ = 0.028, NNT 2 (CI95%: 1.3 - 6.9. No adverse events were recorded including INR < 2 at 24 hours of treatment administration. Our results are consistent with studies where specific oral presentation of Vit-K was used. The results indicate that oral administration of Vit-K, prepared from an intravenous Vit-K preparation, is safe and more effective to revert excessive anticoagulation than simply withholding warfarin, in places where specific preparation of oral Vit-K is not available or too expensive.

  18. Uninterrupted Dabigatran versus Warfarin for Ablation in Atrial Fibrillation

    NARCIS (Netherlands)

    Calkins, Hugh; Willems, Stephan; Gerstenfeld, Edward P.; Verma, Atul; Schilling, Richard; Hohnloser, Stefan H.; Okumura, Ken; Serota, Harvey; Nordaby, Matias; Guiver, Kelly; Biss, Branislav; Brouwer, Marc A.; Grimaldi, Massimo; de Asmundis, Carlo; Debruyne, Philippe; Pierard, Luc; Scavé e, Christophe; Schwagten, Bruno; van Acker, Hannes; van Heuverswyn, Frank; Ayala-Paredes, Felix; Lane, Christopher; Lockwood, Evan; Michael, Kevin; Morillo, Carlos; O’ Hara, Gilles; Cebron, Jean-Pierre; Chevalier, Philippe; DeChillou, Christian; Defaye, Pascal; Deharo, Jean-Claude; Duthoit, Guillaume; Marijon, Eloi; Mechulan, Alexis; Sacher, Fré dé ric; Bonnemeier, Hendrik; Dahme, Tillmann; Ince, H.ü seyin; Neumann, Thomas; Steven, Daniel; Ü cer, Ekrem; Zabel, Markus; Calo, Leonardo; Cireddu, Manuela; Menardi, Endrju; Themistoclakis, Sakis; Tondo, Claudio; Fujii, Kenshi; Iwasa, Atsushi; Inden, Yasuya; Kimura, Masaomi; Murakami, Masato; Murakami, Yoshimasa; Satomi, Kazuhiro; Shimizu, Wataru; Watarai, Masato; Yoshida, Yukihiko; Merino, José -Luí s; Mitjans, Angel Moya; Mont, Lluí s; Asensi, Joaquí n Osca; Pedrote Martí nez, Á ngel Alonso; Teijeira-Ferná ndez, Elvis; Allaart, Cornelis P.; de Jong, Jonas S. G.; Folkeringa, Richard J.; Simmers, Tim A.; Barbarash, Olga L.; Kuznetsov, Vadim; Nedoshivin, Aleksandr; Novikova, Tatiana; Revishvili, Amiran S.; Staroverov, Ilya; Agarwal, Sharad; Betts, Timothy; Connelly, Derek; Hobson, Neil; Leong, Fong; McCready, James; Paisey, John; Tayebjee, Muzahir; Thornley, Andrew; Ahmed, Jameel; Beck, Hiroko; Beinart, Sean; Bindra, Sanjay; Chae, Sanders; Cheng, Jie; Eldadah, Zayd; Feigenblum, David; Fuenzalida, Charles; Gandhavadi, Maheer; Garabelli, Paul; Gerstenfeld, Edward; Gonzalez, Mario; Hurwitz, Jodie; Johnson, Colleen; Kabra, Rajesh; Kowalski, Marcin; Kulkarni, Gurudutt; Marrouche, Nassir; Miller, John; Mounsey, Paul; Norris, Blake; O’ Neill, Gearoid; Roukoz, Henri; Srivatsa, Uma; Talano, James; Vora, Aaditya; Wong, Brian; Camm, John; Cappato, Riccardo; Crijns, Harry; Kenigsberg, David; Tijssen, Jan G. P.; Januzzi, James; Garasic, Joe; Pehrson, Steen; Kolansky, Daniel; McDonald, Michael; van Tosh, Andrew; Sturm, Jonathan; Peeters, André ; Hirsch, Karen

    2017-01-01

    BACKGROUND Catheter ablation of atrial fibrillation is typically performed with uninterrupted anticoagulation with warfarin or interrupted non-vitamin K antagonist oral anticoagulant therapy. Uninterrupted anticoagulation with a non-vitamin K antagonist oral anticoagulant, such as dabigatran, may be

  19. Medical cost reductions associated with the usage of novel oral anticoagulants vs warfarin among atrial fibrillation patients, based on the RE-LY, ROCKET-AF, and ARISTOTLE trials.

    Science.gov (United States)

    Deitelzweig, Steve; Amin, Alpesh; Jing, Yonghua; Makenbaeva, Dinara; Wiederkehr, Daniel; Lin, Jay; Graham, John

    2012-01-01

    The randomized clinical trials, RE-LY, ROCKET-AF, and ARISTOTLE, demonstrate that the novel oral anticoagulants (NOACs) are effective options for stroke prevention among non-valvular atrial fibrillation (AF) patients. This study aimed to evaluate the medical cost reductions associated with the use of individual NOACs instead of warfarin from the US payer perspective. Rates for efficacy and safety clinical events for warfarin were estimated as the weighted averages from the RE-LY, ROCKET-AF and ARISTOTLE trials, and event rates for NOACs were determined by applying trial hazard ratios or relative risk ratios to such weighted averages. Incremental medical costs to a US health payer of an AF patient experiencing a clinical event during 1 year following the event were obtained from published literature and inflation adjusted to 2010 cost levels. Medical costs, excluding drug costs, were evaluated and compared for each NOAC vs warfarin. Sensitivity analyses were conducted to determine the influence of variations in clinical event rates and incremental costs on the medical cost reduction. In a patient year, the medical cost reduction associated with NOAC usage instead of warfarin was estimated to be -$179, -$89, and -$485 for dabigatran, rivaroxaban, and apixaban, respectively. When clinical event rates and costs were allowed to vary simultaneously, through a Monte Carlo simulation, the 95% confidence interval of annual medical costs differences ranged between -$424 and +$71 for dabigatran, -$301 and +$135 for rivaroxaban, and -$741 and -$252 for apixaban, with a negative number indicating a cost reduction. Of the 10,000 Monte-Carlo iterations 92.6%, 79.8%, and 100.0% were associated with a medical cost reduction >$0 for dabigatran, rivaroxaban, and apixaban, respectively. Usage of the NOACs, dabigatran, rivaroxaban, and apixaban may be associated with lower medical (excluding drug costs) costs relative to warfarin, with apixaban having the most substantial medical cost

  20. Genetics Home Reference: warfarin resistance

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions Warfarin resistance Warfarin resistance Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Warfarin resistance is a condition in which individuals have a ...

  1. Warfarin Poisoning with Delayed Rebound Toxicity.

    Science.gov (United States)

    Berling, Ingrid; Mostafa, Ahmed; Grice, Jeffrey E; Roberts, Michael S; Isbister, Geoffrey K

    2017-02-01

    Intentional poisoning with warfarin is not the same as over-anticoagulation, for which guidelines exist. The coagulopathy resulting from a warfarin overdose is reversed with vitamin K 1 , the dose and timing of which is often guided by experience with the management of over-anticoagulation with warfarin therapy, rather than acute overdose. We report a case of a 50-year-old man who ingested an unknown amount of his warfarin, venlafaxine, and paracetamol. He presented with an international normalized ratio (INR) of 2.5, which steadily increased over 24 h to 7, despite receiving an initial 1 mg of vitamin K 1 . He was then treated with 5 mg vitamin K 1 , and once the INR returned to 4.5, 40 h post ingestion, he was discharged home. He was also treated with a full course of acetylcysteine for the paracetamol overdose. The following day his INR rebounded to 8.5 and he suffered a spontaneous epistaxis requiring readmission; he was treated with low titrated doses of vitamin K 1 . The warfarin concentration was 74.6 μg/mL 26 h post ingestion and decreased to 3.7 μg/mL over 72 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case highlights the risk of a rebound elevated INR even 3 days after acute warfarin overdose despite treatment with vitamin K 1 . Understanding the pharmacokinetics of vitamin K 1 in comparison with warfarin, repeat INR testing, and continued treatment with oral vitamin K 1 may help avoid complications of rebound coagulopathy in warfarin overdose. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  2. Updates on the Clinical Evidenced Herb-Warfarin Interactions

    Directory of Open Access Journals (Sweden)

    Beikang Ge

    2014-01-01

    Full Text Available Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of warfarin. This paper presents an update overview of clinical findings regarding herb-warfarin interaction, highlighting clinical outcomes, severity of documented interactions, and quality of clinical evidence. Among thirty-eight herbs, Cannabis, Chamomile, Cranberry, Garlic, Ginkgo, Grapefruit, Lycium, Red clover, and St. John’s wort were evaluated to have major severity interaction with warfarin. Herbs were also classified on account of the likelihood of their supporting evidences for interaction. Four herbs were considered as highly probable to interact with warfarin (level I, three were estimated as probable (level II, and ten and twenty-one were possible (level III and doubtful (level IV, respectively. The general mechanism of herb-warfarin interaction almost remains unknown, yet several pharmacokinetic and pharmacodynamic factors were estimated to influence the effectiveness of warfarin. Based on limited literature and information reported, we identified corresponding mechanisms of interactions for a small amount of “interacting herbs.” In summary, herb-warfarin interaction, especially the clinical effects of herbs on warfarin therapy should be further investigated through multicenter studies with larger sample sizes.

  3. Updates on the clinical evidenced herb-warfarin interactions.

    Science.gov (United States)

    Ge, Beikang; Zhang, Zhen; Zuo, Zhong

    2014-01-01

    Increasing and inadvertent use of herbs makes herb-drug interactions a focus of research. Concomitant use of warfarin, a highly efficacious oral anticoagulant, and herbs causes major safety concerns due to the narrow therapeutic window of warfarin. This paper presents an update overview of clinical findings regarding herb-warfarin interaction, highlighting clinical outcomes, severity of documented interactions, and quality of clinical evidence. Among thirty-eight herbs, Cannabis, Chamomile, Cranberry, Garlic, Ginkgo, Grapefruit, Lycium, Red clover, and St. John's wort were evaluated to have major severity interaction with warfarin. Herbs were also classified on account of the likelihood of their supporting evidences for interaction. Four herbs were considered as highly probable to interact with warfarin (level I), three were estimated as probable (level II), and ten and twenty-one were possible (level III) and doubtful (level IV), respectively. The general mechanism of herb-warfarin interaction almost remains unknown, yet several pharmacokinetic and pharmacodynamic factors were estimated to influence the effectiveness of warfarin. Based on limited literature and information reported, we identified corresponding mechanisms of interactions for a small amount of "interacting herbs." In summary, herb-warfarin interaction, especially the clinical effects of herbs on warfarin therapy should be further investigated through multicenter studies with larger sample sizes.

  4. Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials.

    Science.gov (United States)

    Amin, Alpesh; Deitelzweig, Steve; Jing, Yonghua; Makenbaeva, Dinara; Wiederkehr, Daniel; Lin, Jay; Graham, John

    2014-01-01

    Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (-0.035%/py, p = 0.63). As warfarin's TTR increased from 30 to 90% the estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

  5. Fetal warfarin syndrome.

    Science.gov (United States)

    Sathienkijkanchai, Achara; Wasant, Pornswan

    2005-11-01

    Fetuses exposed to Warfarin in the first trimester of pregnancy have an increased risk of embryopathy which consists of nasal hypoplasia and stippled epiphyses, known as fetal warfarin syndrome or warfarin embryopathy. We herein report a first case of an infant with fetal warfarin syndrome in Thailand. The patient was an offspring of a 34-year-old mother with history of SLE and arterial embolism for several years. She had an unplanned pregnancy while taking warfarin. The patient developed difficulty breathing in the first few hours after birth from severe nasal hypoplasia. He also had short limbs, brachydactyly, nail hypoplasia, and calcifications in the epiphyseal regions of humeri, femora and vertebrae radiographically. The patient eventually died from respiratory failure at 6 months of age.

  6. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

    Science.gov (United States)

    Patel, Manesh R; Mahaffey, Kenneth W; Garg, Jyotsna; Pan, Guohua; Singer, Daniel E; Hacke, Werner; Breithardt, Günter; Halperin, Jonathan L; Hankey, Graeme J; Piccini, Jonathan P; Becker, Richard C; Nessel, Christopher C; Paolini, John F; Berkowitz, Scott D; Fox, Keith A A; Califf, Robert M

    2011-09-08

    The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).

  7. Residues depletion in egg after warfarin ingestion by laying hens.

    Science.gov (United States)

    Kammerer, M; Pouliquen, H; Pinault, L; Loyau, M

    1998-10-01

    Accidental ingestion of anticoagulant rodenticide bait by poultry rarely leads to clinical signs of poisoning, but represents a risk for the consumer because of potential residues in the laid eggs. An assay was conducted for a better risk assessment. Three groups of laying hens were given a single oral dose of 10, 30 or 90 mg warfarin/kg BW. Eggs were collected for 14 d, and warfarin was analyzed by reversed-phase high-performance liquid chromatography. Warfarin was present in the white for 3 to 4 d following anticoagulant ingestion, while concentration increased in the yolk until the 5th or 6th d, and then gradually decreased. At the end of experimentation, warfarin was still detected at below 100 ng/g in the yolk of eggs in each group.

  8. Management of Major Bleeding in Patients With Atrial Fibrillation Treated With Non-Vitamin K Antagonist Oral Anticoagulants Compared With Warfarin in Clinical Practice (from Phase II of the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation [ORBIT-AF II]).

    Science.gov (United States)

    Steinberg, Benjamin A; Simon, DaJuanicia N; Thomas, Laine; Ansell, Jack; Fonarow, Gregg C; Gersh, Bernard J; Kowey, Peter R; Mahaffey, Kenneth W; Peterson, Eric D; Piccini, Jonathan P

    2017-05-15

    Non-vitamin K antagonist oral anticoagulants (NOACs) are effective at preventing stroke in patients with atrial fibrillation (AF). However, little is known about the management of bleeding in contemporary, clinical use of NOACs. We aimed to assess the frequency, management, and outcomes of major bleeding in the setting of community use of NOACs. Using the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation II registry, we analyzed rates of International Society on Thrombosis and Haemostasis major bleeding and subsequent outcomes in patients treated with NOACs versus warfarin. Outcomes of interest included acute and chronic bleeding management, recurrent bleeding, thromboembolic events, and death. In total, 344 patients with atrial fibrillation experienced major bleeding events over a median follow-up of 360 days follow-up: n = 273 on NOAC (3.3 per 100 patient-years) and n = 71 on warfarin (3.5 per 100 patient-years). Intracranial bleeding was uncommon but similar (0.34 per 100 patient-years for NOAC vs 0.44 for warfarin, p = 0.5), as was gastrointestinal bleeding (1.8 for NOAC vs 1.3 for warfarin, p = 0.1). Blood products and correction agents were less commonly used in NOAC patients with major bleeds compared with warfarin-treated patients (53% vs 76%, p = 0.0004 for blood products; 0% vs 1.5% for recombinant factor; p = 0.0499); no patients received pharmacologic hemostatic agents (aminocaproic acid, tranexamic acid, desmopressin, aprotinin). Within 30 days, 23 NOAC-treated patients (8.4%) died versus 5 (7.0%) on warfarin (p = 0.7). At follow-up, 126 NOAC-treated (46%) and 29 warfarin-treated patients (41%) were not receiving any anticoagulation. In conclusion, rates of major bleeding are similar in warfarin and NOAC-treated patients in clinical practice. However, NOAC-related bleeds require less blood product administration and rarely require factor replacement. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights

  9. Pharmacogenomics of warfarin: uncovering a piece of the warfarin mystery.

    Science.gov (United States)

    Gulseth, Michael P; Grice, Gloria R; Dager, William E

    2009-01-15

    The literature on the pharmacogenomics of warfarin and the use of genetic testing to optimize initial and maintenance warfarin dosing is reviewed. Warfarin tablets contain a racemic mixture of R- and S-isomers. The S-isomer is responsible for about 70% of warfarin's anticoagulant effect. Cytochrome P-450 isoenzyme 2C9 (CYP2C9) metabolizes S-warfarin into two inactive metabolites. Genetic variations to the gene encoding CYP2C9 (CYP2C9 ) are known to affect warfarin clearance. Single nucleotide polymorphisms (SNPs) have been identified that clearly influence warfarin metabolism and sensitivity, including SNP variants of CYP2C9 and SNPs in vitamin K epoxide reductase complex subunit 1 (VKORC1), which influence an individual's sensitivity to a given dose. Retrospective studies have evaluated potential factors influencing warfarin metabolism, maintenance dosing, and variability. Several dosing models used to predict warfarin dosing (initial or refinement) have been retrospectively evaluated in diverse patient populations. There are several arguments to support incorporating its use in current clinical practice; however, many expert clinicians in anticoagulation have expressed concern that the push for genotyping patients for CYP2C9 and VKORC1 is premature and not based on good, prospective evidence. Large, randomized controlled trials, in multiple patient populations, comparing clinical dosing to genetic-guided dosing are needed to fully determine the benefits of pharmacogenetic warfarin dosing. The increased understanding of pharmacogenomics may improve patient safety during initial dosing of warfarin. At this time, it is unknown if genotype-based dosing will become the standard of care for patients receiving the drug.

  10. Major Interaction between Warfarin and Na Valproate: A Case Report

    Directory of Open Access Journals (Sweden)

    Bizhan Kouchaki

    2015-10-01

    Full Text Available  Abstract: Warfarin is the most commonly used oral anticoagulant drug in clinical practice with extreme inter and intra-individual variation in pharmacokinetic properties. Na Valproate, a broad spectrum anticonvulsant agent, is best known for its enzyme inhibition properties and also displacement of protein binding sites. Interaction between Warfarin and psychotropic drugs including Valproate are important and perhaps under recognized. In this report, we present a 48 year old female patient with chief complaints of abdominal pain, tea-color urine, blurred vision and headache. She had been suffering from "migraine headache" for 15 years that was relatively well controlled with Na Valproate 200mg twice daily. She was experienced a deep vein thrombosis (DVT following oral contraceptive. For management of DVT, she was received Warfarin 5mg/day which was increased to 7.5 mg /day after 2 weeks. Three days after this increment of dose, her Prothrombin Time (PT rose to 35.3 seconds (three times of normal value and evidences of bleeding including hematuria and hematemesis were observed. Based on  the history and laboratory findings, "Warfarin toxicity" was the first impression and she was treated with fresh frozen plasma and vitamin K with a well recovery. This experience emphasizes the clinical significant interaction between Warfarin and Na Valproate, which may take place even with the usual doses of each agent.  

  11. Algorithms for monitoring warfarin use: Results from Delphi Method.

    Science.gov (United States)

    Kano, Eunice Kazue; Borges, Jessica Bassani; Scomparini, Erika Burim; Curi, Ana Paula; Ribeiro, Eliane

    2017-10-01

    Warfarin stands as the most prescribed oral anticoagulant. New oral anticoagulants have been approved recently; however, their use is limited and the reversibility techniques of the anticoagulation effect are little known. Thus, our study's purpose was to develop algorithms for therapeutic monitoring of patients taking warfarin based on the opinion of physicians who prescribe this medicine in their clinical practice. The development of the algorithm was performed in two stages, namely: (i) literature review and (ii) algorithm evaluation by physicians using a Delphi Method. Based on the articles analyzed, two algorithms were developed: "Recommendations for the use of warfarin in anticoagulation therapy" and "Recommendations for the use of warfarin in anticoagulation therapy: dose adjustment and bleeding control." Later, these algorithms were analyzed by 19 medical doctors that responded to the invitation and agreed to participate in the study. Of these, 16 responded to the first round, 11 to the second and eight to the third round. A 70% consensus or higher was reached for most issues and at least 50% for six questions. We were able to develop algorithms to monitor the use of warfarin by physicians using a Delphi Method. The proposed method is inexpensive and involves the participation of specialists, and it has proved adequate for the intended purpose. Further studies are needed to validate these algorithms, enabling them to be used in clinical practice.

  12. The king is dead (warfarin): direct thrombin and factor Xa inhibitors: the next Diadochian War?

    Science.gov (United States)

    Diener, Hans-Christoph; Eikelboom, John; Granger, Christopher B; Hacke, Werner

    2012-02-01

    Atrial fibrillation is an important risk factor for stroke. New drugs for oral anticoagulation that do not exhibit the limitations of vitamin K antagonists like warfarin are under investigation. These include direct factor Xa inhibitors and direct thrombin-inhibitors. Recent studies provide promising results for apixaban, dabigatran, and rivaroxaban, including higher efficacy and significantly lower incidences of intracranial bleeds compared with warfarin. The new oral anticoagulants substances show similar results in secondary as in primary stroke prevention in patients with AF and will on the long run replace warfarin.

  13. Dabigatran versus warfarin in the treatment of acute venous thromboembolism

    NARCIS (Netherlands)

    Schulman, Sam; Kearon, Clive; Kakkar, Ajay K.; Mismetti, Patrick; Schellong, Sebastian; Eriksson, Henry; Baanstra, David; Schnee, Janet; Goldhaber, Samuel Z.; Schulman, S.; Eriksson, H.; Goldhaber, S.; Kakkar, A.; Kearon, C.; Mismetti, P.; Schellong, S.; Minar, E.; Bergqvist, D.; Tijssen, J.; Prins, M. [=Martin H.; Büller, H.; Otten, J.; Peters, R.; Mac Gillavry, M.; Pol, S.; Burroughs, A.; Gilmore, I.; Bluguermann, J.; Carlevaro, O.; Dipaola, L.; Gitelman, P.; Santos, D.; Schygiel, P.; Baker, R.; Blombery, P.; Gallus, A.; Gan, E.; Gibbs, H.; Salem, H.; Baghestanian, M.; Pilger, E.; Sturm, W.; Debing, E.; Gadisseur, A.; Hainaut, P.; Verhamme, P.; Wautrecht, J.-C.; Zicot, M.; Bizzachi, J. M. Annichino; Araujo, G.; de Araujo, J. Dalmo; Panico, F. M. Duarte Brandão; Nagato, Y.; Pereira, A. H.; Leao, P. Puech; Ramaciotti, E.; Moreira, R. C. Rocha; Timi, J.; Anderson, D.; Crowther, M.; Dolan, S.; Eikelboom, J.; Spencer, F.; Game, M.; Kahn, S.; Kassis, J.; Klinke, P.; Kovacs, M.; Milot, A.; Ritchie, B.; Rodger, M.; Solymoss, S.; Villeneuve, J.; Yeo, E.; Cervinka, P.; Homza, M.; Hrdy, P.; Klimsa, Z.; Lang, P.; Maly, R.; Oral, I.; Reichert, P.; Spinar, J.; Varejka, P.; Vladimir, J.; Brønnum-Schou, J.; Jensen, S.; Jensen, S. E.; Kristensen, K. S.; Nielsen, H.; Wiemann, O.; Bost, V.; Buchmuller, A.; Guillot, K.; Laurent, P.; Lecomte, F.; Mottier, D.; Quere, I.; Wahl, D.; Beyer, J.; Dormann, A.; Hoffmann, U.; Maier, M.; Mietaschk, A.; Katsenis, K.; Klonaris, C.; Liappis, C.; Acsady, G.; Berhes, I.; Boda, Z.; Farkas, K.; Jakucs, J.; Kollar, L.; Matyas, L.; Riba, M.; Sereg, M.; Aggarwal, R.; Banker, D.; Bharani, A.; Gadkari, M.; Hiremath, J.; Jain, A.; Kareem, S.; Lyengar, S.; Parakh, R.; Sekar, N.; Srinivas, A.; Suresh, K.; Vujay, T.; Brenner, B.; Efrati, S.; Elias, M.; Gavish, D.; Grossman, E.; Lahav, M.; Lishner, M.; Zeltser, D.; Agnelli, G.; Cimminiello, C.; Palareti, G.; Prandoni, P.; Santonastaso, M.; Silingardi, M.; Lee, E. Aldrett; Andrade, J. M. Fontes; Valles, J. Jaurrieta; Biesma, D.; Dees, A.; Fijnheer, R.; Hamulyak, K.; Kramer, M. H. H.; Leebeek, F. W. G.; Lieverse, L.; Nurmohamed, M. T.; Chunilal, S.; Jackson, S.; Ockelford, P.; Smith, M.; Njaastad, A. M.; Sandseth, P. M.; Tveit, A.; Waage, A.; Barata, J.; Capitao, M.; Fernandes, F. E.; Leitão, A.; Providência, L.; Alohin, D. I.; Belentsov, S.; Chernyatina, M.; Chernyavsky, A.; Fokin, A.; Gubenko, A.; Guz, V. Alexander V.; Katelnitsky, I.; Khamitov, A. A. A.; Khitaryan, A.; Khubulava, G.; Mikhailov, I.; Shkurin, V.; Staroverov, I.; Tchumakov, A.; Zaporozhsky, A.; Duris, T.; Poliacik, P.; Spisak, V.; Szentivanyi, M.; Zubek, V.; Adler, D.; Kelbe, D.; Le Roux, D.; Pieterse, A.; Routier, R.; Siebert, R.; Sloane, B.; Smith, C.; van Rensburg, H.; del Toro, J.; García-Fuster, M. J.; Mateo, J.; Monreal, M.; Nieto, J. A.; Sánchez-Molini, P.; Sedano, C.; Trujillo, J.; Valle, R.; Villalta, J.; Aagesen, J.; Carlsson, A.; Johansson, L.; Lärfars, G.; Lindmarker, P.; Säfvenberg, U.; Själander, A.; Bengisun, U.; Calkavur, T.; Guney, M. R.; Karahan, S.; Kurtoglu, M.; Sakinci, U.; Gubka, A.; Mishalov, V.; Skupyy, O.; Cohen, A.; Keeling, D.; Kesteven, P.; MacCallum, P.; Maclean, R.; Shah, P.; Watson, H.; Bartkowiak, A.; Bolster, E.; Botnick, W. C.; Burnett, B.; Chervu, A.; Comerota, A. J.; Dy, N. M.; Fulco, F. A.; Gossage, J. R.; Kaatz, S.; Lahiri, B.; Lerner, R. G.; Masson, J. A.; Moll, S.; Morganroth, M.; Patel, K.; Paulson, R.; Powell, R.; Samson, R.; Seibert, A.; Spyropoulos, A.; Vrooman, P. S.

    2009-01-01

    BACKGROUND: The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism. METHODS: In a randomized, double-blind, noninferiority trial involving patients with acute venous

  14. Edoxaban versus warfarin in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Giugliano, Robert P; Ruff, Christian T; Braunwald, Eugene

    2013-01-01

    BACKGROUND: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. METHODS: We conducted a randomized, double-blind, double-dummy trial comparing t...

  15. Dabigatran versus warfarin in patients with atrial fibrillation

    NARCIS (Netherlands)

    Connolly, Stuart J.; Ezekowitz, Michael D.; Yusuf, Salim; Eikelboom, John; Oldgren, Jonas; Parekh, Amit; Pogue, Janice; Reilly, Paul A.; Themeles, Ellison; Varrone, Jeanne; Wang, Susan; Alings, Marco; Xavier, Denis; Zhu, Jun; Diaz, Rafael; Lewis, Basil S.; Darius, Harald; Diener, Hans-Christoph; Joyner, Campbell D.; Wallentin, Lars; Connolly, S. J.; Ezekowitz, M. D.; Yusuf, S.; Eikelboom, J.; Oldgren, J.; Parekh, A.; Reilly, P. A.; Themeles, E.; Varrone, J.; Wang, S.; Palmcrantz-Graf, E.; Haehl, M.; Wallentin, L.; Alings, A. M. W.; Amerena, J. V.; Avezum, A.; Baumgartner, I.; Brugada, J.; Budaj, A.; Caicedo, V.; Ceremuzynski, L.; Chen, J. H.; Commerford, P. J.; Dans, A. L.; Darius, H.; Di Pasquale, G.; Diaz, R.; Erol, C.; Ferreira, J.; Flaker, G. C.; Flather, M. D.; Franzosi, M. G.; Gamboa, R.; Golitsyn, S. P.; Gonzalez Hermosillo, J. A.; Halon, D.; Heidbuchel, H.; Hohnloser, S. H.; Hori, M.; Huber, K.; Jansky, P.; Kamensky, G.; Keltai, M.; Kim, S.; Lau, C. P.; Le Heuzey, J. Y. F.; Lewis, B. S.; Liu, L. S.; Nanas, J.; Razali, O.; Pais, P. S.; Parkhomenko, A. N.; Pedersen, K. E.; Piegas, L. S.; Raev, D.; Simmers, T. A.; Smith, P. J.; Talajic, M.; Tan, R. S.; Tanomsup, S.; Toivonen, L.; Vinereanu, D.; Xavier, D.; Zhu, J.; Diener, H. C.; Joyner, C. D.; Diehl, A.; Ford, G.; Robinson, M.; Silva, J.; Sleight, P.; Wyse, D. G.; Collier, J.; de Mets, D.; Hirsh, J.; Lesaffre, E.; Ryden, L.; Sandercock, P.; Anastasiou-Nana, M. I.; Andersen, G.; Annex, B. H.; Atra, M.; Bornstein, N. M.; Boysen, G.; Brouwers, P. J. A. M.; Buerke, M.; Burrell, L. M.; Chan, Y. K.; Chen, W. H.; Cheung, R. T. F.; Divakaramenon, S.; Donnan, G. A.; Duray, G. Z.; Dvorakova, H.; Fiedler, J.; Gardinale, E.; Gates, P. C.; Goshev, E. G.; Goto, S.; Gross, B.; Guimaraes, H. P.; Gulkevych, O.; Haberl, R. L.; Hankey, G.; Hartikainen, J.; Healey, J.; Iliesiu, A. M.; Irkin, O.; Jaxa-Chamiec, T.; Jolly, S.; Kaste, K. A. M.; Kies, B.; Kostov, K. D.; Kristensen, K. S.; Labovitz, A. J.; Lassila, R. P. T.; Lee, K. L. F.; Lutay, Y. M.; Magloire, P.; Mak, K. H.; Meijer, A.; Mihov, L.; Morillo, C. A.; Morillo, L. E.; Nair, G. M.; Norrving, B.; Ntalianis, A.; Ntsekhe, M.; Olah, L.; Pasco, P. M. D.; Peeters, A.; Perovic, V.; Petrov, I.; Pizzolato, G.; Rafti, F.; Rey, N. R.; Ribas, S.; Rokoss, M.; Sarembock, I. J.; Sheth, T.; Shuaib, A.; Sitkei, E.; Sorokin, E.; Srámek, M.; Strozynska, E.; Tanne, D.; Thijs, V. N. S.; Tomek, A.; Turazza, F.; Vanhooren, G.; Vizel, S. A.; Vos, J.; Wahlgren, N.; Weachter, R.; Zaborska, B.; Zaborski, J.; Zimlichman, R.; Cong, J.; Fendt, K.; Muldoon, S.; Bajkor, S.; Grinvalds, A.; Malvaso, M.; Pogue, J.; Simek, K.; Yang, S.; Alzogaray, M. F.; Bono, J. O.; Caccavo, A.; Cartasegna, L.; Casali, W. P.; Cuello, J. L.; Cuneo, C. A.; Elizari, M. V.; Fernandez, A. A.; Ferrari, A. E.; Gabito, A. J.; Goicoechea, R. F.; Gorosito, V. M.; Hirschson, A.; Hominal, M. A.; Hrabar, A. D.; Liberman, A.; Mackinnon, I. J.; Manzano, R. D.; Muratore, C. A.; Nemi, S. A.; Rodriguez, M. A.; Sanchez, A. S.; Secchi, J.; Vogel, D. R.; Colquhoun, D. M.; Crimmins, D. S.; Dart, A. M.; Davis, S. M.; Hand, P. J.; Kubler, P. A.; Lehman, R. G.; McBain, G.; Morrison, H. C.; New, G.; Singh, B. B.; Spence, C. Z.; Waites, J. H.; Auer, J.; Doweik, L.; Freihoff, F.; Gaul, G.; Gazo, F.; Geiger, H.; Giacomini, G.; Huber, G. W.; Jukic, I.; Lamm, G.; Niessner, H.; Podczeck, A.; Schuh, J.; Siostrzonek, P.; Steger, C.; Vogel, B.; Watzak, R.; Weber, H. S.; Weihs, W.; Blankoff, I.; Boland, J. L.; Brike, C.; Carlier, M.; Cools, F.; de Meester, A.; de Raedt, H. J.; de Wolf, L.; Dhooghe, G. M.; Dilling-Boer, D.; Elshot, S. R.; Fasseaux, S.; Goethals, M.; Goethals, P.; Gurne, O.; Hellemans, S.; Ivan, B.; Jottrand, M.; Kersschot, I.; Lecoq, E.; Marcovitch, O.; Melon, D.; Miljoen, H.; Missault, L.; Pierard, L. A.; Provenier, F.; Rousseau, M. F.; Stockman, D.; Tran-Ngoc, E.; van Mieghem, W.; Vandekerckhove, Y.; Vandervoort, P.; Verrostte, J.; Vijgen, J.; Armaganijan, D.; Braga, C.; Braga, J. C. F.; Cipullo, R.; Cunha, C. L. P.; de Paola, A.; Delmonaco, M. I.; Guimaraes, F. V.; Herek, L.; Kerr Saraiva, J. F.; Maia, L. N.; Lorga, A. M.; Lorga-Filho, A. M.; Marino, R. L.; Melo, C. S.; Mouco, O. M.; Pereira, V. C.; Precoma, D. B.; Rabelo, W.; Rassi, S.; Rossi, P. R.; Rossi Neto, J. M.; Silva, F. M.; Vidotti, M. H.; Zimmermann, S. L.; Anev, E. D.; Balabanov, T. A.; Baldjiev, E. S.; Bogusheva, E. S.; Chaneva, M. A.; Filibev, I. G.; Gotcheva, N. N.; Goudev, A. R.; Gruev, I. T.; Guenova, D. T.; Kamenova, Z. A.; Manov, E. I.; Panov, I. A.; Parvanova, Z. I.; Pehlivanova, M. B.; Penchev, P. T.; Penkov, N. Y.; Radoslavov, A. L.; Ramshev, K. N.; Runev, N. M.; Sindzhielieva, M. N.; Spirova, D. A.; Tsanova, V. M.; Tzekova, M. L.; Yaramov, G. K.; Aggarwal, R.; Bakbak, A. I.; Bayly, K.; Berlingieri, J. C.; Blackburn, K.; Bobbie, C.; Booth, A. W.; Borts, D.; Bose, S.; Boucher, P.; Brown, K.; Burstein, J. M.; Butt, J. C.; Carlson, B. D.; Chetty, R.; Chiasson, J. D.; Constance, C.; Costi, P.; Coutu, B.; Deneufbourg, I.; Dion, D.; Dorian, P.; Douketis, J. D.; Farukh, S.; Filipchuk, N. G.; Fox, B. A.; Fox, H. I.; Gailey, C. B.; Gauthier, M.; Glanz, A.; Green, M. S.; Habot, J.; Hink, H.; Kearon, C.; Kouz, S.; Lai, C.; Lai, K.; Lalani, A. V.; Lam, A. S.; Lapointe, L. A.; Leather, R. A.; Ma, P. T. S.; MacKay, E.; Mangat, I.; Mansour, S.; Melton, E.; Mitchell, L. B.; Morris, A. L.; Nisker, W. A.; O'Donnell, M. J.; O'Hara, G.; Omichinski, L. M.; Pandey, A. S.; Parkash, R.; Pesant, Y.; Pilon, C.; Pistawka, K. J.; Powell, C. N.; Price, J. B.; Prieur, S.; Rebane, T. M.; Ricci, A. J.; Roberge, J.; Roy, M.; Sapp, J. L.; Savard, D.; Schulman, S.; Sehl, M. J.; Sestier, F.; Shandera, R.; Shu, D.; Sterns, L. D.; St-Hilaire, R.; Syan, G. S.; Talbot, P.; Teitelbaum, I.; Tytus, R. H.; Winkler, L.; Zadra, R.; Zidel, B. S.; Bai, X. J.; Gao, W.; Gao, X.; Guan, D. M.; He, Z. S.; Hua, Q.; Li, H.; Li, L.; Li, W. M.; Lu, G. P.; Lv, S.; Meng, K.; Niu, H. Y.; Qi, D. G.; Qi, S. Y.; Qian, F.; Sun, N. L.; Wang, H. Y.; Wang, N. F.; Yang, Y. M.; Zeng, H.; Zhang, F.; Zhang, F. R.; Zhang, L.; Bohorquez, R.; Rosas, J. F.; Saent, L.; Vacca, M.; Velasco, V. M.; Belohlavek, J.; Cernohous, M.; Choura, M.; Dedek, V.; Filipensky, B.; Hemzsky, L.; Karel, I.; Kopeckova, I.; Kovarova, K.; Labrova, R.; Madr, T.; Poklopova, Z.; Rucka, D.; Simon, J.; Skalicka, H.; Smidova, M.; Spinar, J.; Dodt, K. K.; Egstrup, K.; Friberg, J.; Haar, D.; Husted, S.; Jensen, G. V.; Joensen, A. M.; Klarlund, K. K.; Lind Rasmussen, S.; Melchior, T. M.; Olsen, M. E.; Poulsen, M. K.; Ralfkiaer, N.; Rasmussen, L. H.; Skagen, K.; Airaksinen, K. E.; Huikuri, H. V.; Hussi, E. J.; Kettunen, P.; Mänttäri, M.; Melin, J. H.; Mikkelsson, J.; Peuhkurinen, K.; Virtanen, V. K.; Ylitalo, A.; Agraou, B.; Boucher, L.; Bouvier, J. M.; Boye, A.; Boye, B.; Decoulx, E. M.; Defaye, P.; Delay, M.; Desrues, H.; Gacem, K.; Igigabel, P.; Jacon, P.; Leparree, S.; Magnani, C.; Martelet, M.; Movallem, J.; Olive, T.; Poulard, J. E.; Tiam, B.; Appel, K. F.; Appel, S.; Bansemir, L.; Borggrefe, M.; Brachmann, J.; Bulut-Streich, N.; Busch, K.; Dempfle, C. E. H.; Desaga, M.; Desaga, V.; Dormann, A.; Fechner, I.; Genth-Zotz, S.; Haberbosch, W. G.; Harenberg, J.; Haverkamp, W. L.; Henzgen, R.; Heuer, H.; Horacek, T.; Huttner, H. B.; Janssens, U.; Jantke, H. J.; Klauss, V.; Koudonas, D.; Kreuzer, J.; Kuckuck, H.; Maselli, A.; Müegge, A.; Munzel, T. F.; Nitsche, K.; Nledegjen, A.; Parwani, A.; Pluemer-Schmidt, M.; Pollock, B. W.; Salbach, B. I.; Salbach, P. B.; Schaufele, T.; Schoels, W.; Schwab, S.; Siegmund, U.; Veltkamp, R.; Von Hodenberg, E.; Weber, R.; Zechmeister, M.; Anastasopoulous, A. A.; Foulidis, V. O.; Kaldara, E.; Karamitsos, K.; Karantzis, J.; Kirpizidis, H.; Kokkinakis, C.; Krommydas, A.; Lappas, C.; Lappas, G. I.; Manolis, A.; Manolis, A. S.; Orfanidis, Z.; Papamichalis, M.; Peltekis, L.; Savvas, S.; Skoumpourdis, E. A.; Stakos, D. A.; Styliadis, I.; Triposkiadis, F.; Tsounis, D.; Tziakas, D. N.; Zafiridis, T.; Zarifis, J. H.; Chan, G. C. P.; Chan, W. K.; Chan, W. S.; Lau, C. L.; Tse, H. F.; Tsui, P. T.; Yu, C. M.; Yue, C. S.; Fugedi, K.; Garai, B.; Jánosi, A.; Kadar, A.; Karpati, P.; Keltai, K.; Kosa, I.; Kovacs, I.; Laszlo, Z.; Mezei, L.; Rapi, J.; Regos, L. I.; Szakal, I.; Szigyarto, I.; Toth, K.; Zsa'ry, A.; Agarwal, D. K.; Aggarwal, R. K.; Arulvenkatesh, R.; Bharani, A.; Bhuvaneswaran, J. S.; Byrapaneni, R. B.; Chandwani, P.; Chopra, S.; Desai, N.; Deshpande, V.; Golla, N. P.; Gupta, J. B.; Haridas, K. K.; Hiremath, J.; Jain, A. S.; Jain, M.; Jhala, D. A.; Joseph, J.; Kaila, M.; Kannaiyan, A.; Kumar, S.; Kuruvila, P.; Mahorkar, V. K.; Metha, A.; Naik, A. M.; Narayanan, S.; Panwar, R. B.; Reddy, C.; Sawhney, J. P. S.; Shah, S. M.; Sharma, S.; Shetty, G. S.; Sinha, N.; Sontakke, N. N.; Srinivas, A.; Trivedi, M. R.; Vadagenalli, P. S.; Vijayakumar, M.; Ben-Aharon, Y.; Benhorin, J.; Bogomolny, N.; Botwin-Shimko, S.; Bova, I.; Brenner, B.; Burstein, M.; Butnaru, A.; Caspi, A.; Danenberg, H. D.; Dayan, M.; Eldar, M.; Elian, D.; Elias, M.; Elis, A.; Esanu, G.; Genin, I.; Goldstein, L. H.; Grossman, E.; Hamoud, S.; Hayek, T.; Ilani, N.; Ilia, R.; Klainman, E. I.; Leibowitz, A.; Leibowitz, D.; Levin, I.; Lishner, M.; Lotan, C.; Mahagney, A.; Marmor, A.; Motro, M.; Peres, D.; Plaev, T.; Reisen, L. H.; Rogowski, O.; Schwammenthal, E.; Schwammenthal, Y.; Shechter, M.; Shochat, M.; Shotan, A.; Strasberg, B.; Sucher, E.; Telman, G.; Turgeman, Y.; Tzoran, I.; Weiss, A. T.; Weitsman, T.; Weller, B.; Wexler, D. H.; Wolff, R.; Yarnitsky, D.; Zeltser, D.; Argiolas, G.; Arteni, F.; Barbiero, M.; Bazzucco, R.; Bernardi, D.; Bianconi, L.; Bicego, D.; Brandini, R.; Bresciani, B.; Busoni, F.; Carbonieri, E.; Carini, M.; Catalano, A.; Cavallini, C.; D'Angelo, G.; de Caterina, R.; Di Niro, M.; Filigheddu, F.; Fraticelli, A.; Marconi, R.; Mennuni, M.; Moretti, L.; Mos, L.; Pancaldi, L. G.; Pirelli, S.; Renda, G.; Santini, M.; Tavarozzi, I.; Terrosu, P.; Uneddu, F.; Viccione, M.; Zanini, R.; Zingarini, G.; Aoyagi, T.; Eguma, H.; Fujii, K.; Fukuchi, M.; Fukunami, M.; Furukawa, Y.; Furuya, J.; Haneda, K.; Hara, S.; Hiroe, M.; Iesaka, Y.; Iijima, T.; Ishibashi, Y.; Iwade, K.; Kajiya, T.; Kakinoki, S.; Kamakura, S.; Katayama, Y.; Kihara, Y.; Kimura, K.; Kobayashi, S.; Kono, K.; Koretsune, Y.; Marui, N.; Matsuyama, T.; Meno, H.; Miyamoto, N.; Morikawa, S.; Myojin, K.; Nakamura, T.; Nishi, Y.; Ogawa, T.; Onaka, H.; Sakakibara, T.; Sakurai, S.; Sasaki, Y.; Sato, H.; Sugii, M.; Sumii, K.; Suzuki, S.; Takagi, M.; Takenaka, T.; Takeuchi, K.; Tanaka, S.; Tanouchi, J.; Ueda, K.; Ueyama, Y.; Ujihira, T.; Usui, M.; Yagi, M.; Yamada, T.; Yamamoto, H.; Yokochi, M.; Zen, E.; Abd Ghaphar, A. K.; Ang, C. K.; Chee, K. H.; Fong, A. F. Y.; Ismail, O.; Jeyaindran, S.; Kaur, S.; Lee, T. C.; Sandhu, R. S.; Shah, R. P.; Suganthi, S.; Zainal Abidin, S.; Alvarado-Ruiz, R.; Carrillo, J.; Delgado, E.; Fernandez Bonetti, P. A.; Leiva, J. L.; Meaney, A.; Olvera, R.; Peralta-Heredia, R.; Rodriguez, I.; Ruiz Rabasa, C. M.; Solache, G.; Villeda Espinosa, E.; Ahmed, S.; Badings, E.; Bartels, G. L.; Beganovic, M.; Bruning, T. A.; Ciampricotti, R.; Cozijnsen, L.; Crijns, H. J.; Daniels, M. C. G.; de Waard, D. E. P.; den Hartog, F. R.; Dirkali, A.; Groenemeijer, B. E.; Heesen, W. F.; Heijmeriks, J. A.; Hoogslag, P. A.; Huizenga, A.; Idzerda, H. H.; Kragten, J. A.; Krasznai, K.; Lenderink, T.; Liem, A. H.; Linssen, G. C.; Lok, D. J.; Meeder, J. G.; Michels, H. R.; Plomp, J.; Pos, L.; Posma, J. L.; Postema, P. G.; Salomonsz, R.; Stoel, I.; Tans, J. G.; Thijssen, H. J.; Timmermans, A. J. M.; Tteleman, R. G.; van Bergen, P. F. M. M.; van de Klippe, H. A.; van der Zwaan, C.; van Eck, J. W. M.; van Es, A. J. J.; van Gelder, I. C.; van Kempen, L. H.; van Kesteren, H. A.; van Rossum, P.; Veldmeyer, S.; Wilde, A. A. M.; Arnesen, H.; Atar, D.; Breder, O.; Istad, H.; Radunovic, Z.; Rykke, D. E.; Sirnes, P. A.; Tveit, A.; Ulimoen, S. R.; Cabrera, W.; Duenas, R.; Heredia, J. M.; Horna, M. E.; Hurtado, Y.; Salazar, P. M.; Abola, M. T. B.; Anonuevo, J. C.; Arellano, R. S.; Dioquino, C.; Morales, D. D.; Reyes, E. B.; Rogelio, G. G.; Roxas, A. A.; Sulit, D. J. V.; Bacior, B.; Dulak, E.; Gniot, J.; Goncikowski, J.; Grodecki, J.; Kalarus, Z. F.; Kawecka-Jaszcz, K.; Miekus, P.; Monies, F.; Piepiorka, M.; Pilichowska, E.; Plizio, E.; Rekosz, J.; Rybicka-Musialik, A.; Streb, W. A.; Styczkiewicz, M.; Szpajer, M.; Trusz-Gluza, M.; Wasilewska-Piepiorka, A.; Adragao, P.; Branco, V.; Canhão, P.; Cunha, L.; Falcão, F.; Lopes, G.; Machado, C.; Martinez-Marcos, J.; Monteiro, P. F.; Parreira, L.; Pinto, A. N.; Providencia, L. A.; Salgado, A. V.; Santos, J. F.; Timoteo, A. T.; Capalneanu, R.; Cinteza, M. A.; Margulesai, A. D.; Turdeanu, D. S.; Vintila, V. D.; Baranov, V. L.; Berngardt, E. R.; Dzhordzhikiya, T. R.; Gordeev, I. G.; Grigoryev, Y. V.; Isaeva, M. U.; Ivleva, A. Y.; Kokorin, V. A.; Komarov, A. L.; Maximenko, O. K.; Maykov, E. B.; Novikova, N.; Novikova, T. N.; Panchenko, E. P.; Poltavskaya, M. G.; Popova, Y. N.; Pronina, S. A.; Revishvili, A. Sh; Shlyakhto, E. V.; Shustov, S. B.; Sidorenko, B. A.; Sinopalnikov, A. I.; Sulimov, V.; Syrkin, A. L.; Titkov, A. Y.; Titkov, Y. S.; Zateyshchikov, D. A.; Zavaritskaya, O. P.; Chia, P. L.; Foo, D.; Sim, K. L.; Bugan, V.; Buganova, I.; Dúbrava, J.; Kaliska, G.; Masarovicova, M.; Mikes, P.; Mikes, Z.; Murin, J.; Pella, D.; Rybar, R.; Sedlák, J.; Skamla, M.; Spurný, P.; Strbova, J.; Uhliar, R.; Disler, L. J.; Engelbrecht, J. M.; Jankelow, D.; King, J.; Klug, E. Q.; Munnick, M.; Okreglicki, A. M.; Routier, R. J.; Snyders, F. A.; Theron, H. D.; Wittmer, H.; Cha, T. J.; Cho, J. G.; Choi, I. S.; Choi, J. I.; Choi, K. J.; Han, K. R.; Heo, J. H.; Jang, S. W.; Kang, T. S.; Kim, H. S.; Kim, K. S.; Kim, S. J.; Kim, S. S.; Kim, Y. H.; Kim, Y. N.; Lee, M. H.; Lee, M. Y.; Nam, G. B.; Oh, D. J.; Park, H. W.; Park, J. S.; Rho, T. H.; Shin, D. G.; Shin, E. K.; Alonso, J. J.; Cano, L.; Castellano, N. P.; Criado-Millan, A. J.; Curcio, A.; Egea, P.; Escudier, J. M.; Grande, A.; Grande, J. M.; Gusi-Tragant, G.; Lozano, I. F.; Martin, A. M.; Martinez-Rubio, A.; Mont, L.; Perez-Villacastin, J.; Sosa, L.; Ali, M.; Andersson, T.; Bandh, S.; Blomstrom Lundqvist, C. M.; Cherfan, P.; Fengsrud, E.; Fluur, C.; Herlitz, J.; Hijazi, Z.; Hoglund, N.; Hojeberg, B.; Jabro, J.; Juhlin, T.; Kjellman, B.; Lonnberg, I.; Maru, F.; Morlid, L.; Nilsson, O. R.; Ronn, F.; Rosenqvist, M.; Walfridsson, H.; Engelter, S. T.; Gallino, A.; Lyrer, P. A.; Moccetti, T.; Petrova, I.; Chang, Y. J.; Chen, C. H.; Chen, M. Y. C.; Cheng, J. J.; Chiang, T. R.; Chung, W. T.; Hsia, C. H.; Hsu, C. Y.; Hu, H. H.; Jeng, J. S.; Lai, W. T.; Lien, L. M.; Lin, K. H.; Liu, C. H.; Lo, H. S.; Peng, G. S.; Po, H. L.; Ryu, S. J.; Tsai, C. D.; Tsai, L. M.; Tseng, C. D.; Wang, J. H.; Wang, S. F.; Yang, S. P.; Kiatchoosakun, S.; Krittayaphong, R.; Kuanprasert, S.; Ngarmukos, T.; Simtharakaew, T.; Sukanandachai, B.; Sukonthasam, A.; Suwanagool, A.; Tatsanavivat, P.; Atmaca, Y.; Baris, N.; Boyaci, B.; Demir, M.; Guneri, S.; Usal, A.; Yalcin, R.; Amosova, K. M.; Beregova, O. P.; Besaga, Y. E. M.; Ikorkin, M. R.; Karapetyan, K.; Karpenko, O. I.; Kononenko, L.; Kuryata, O.; Martynova, L.; Motylevska, T.; Okhryamkina, O.; Pavlyk, S. S.; Perepelytsya, M. V.; Rudenko, L. V.; Skarzhevsky, O. A.; Tkachenko, L. A.; Tseluyko, V.; Usan, N.; Voronkov, L. G.; Yshchenko, K. V.; Zharinov, O. J.; Bryson, V. G.; Butler, R.; Cargill, R. I.; Chahal, N. S.; Cleland, J. G.; Cohen, A. T.; Cruddas, E. M.; Davey, P.; Davies, J.; Ford, S. L.; Griffith, K.; Haynes, R.; Hill, S.; Javed, M.; Kadr, H. H.; Lip, G. H.; Machin, J.; McEneaney, D. J.; McInnes, G. T.; McNeill, A. J.; Moriarty, A. J.; Muir, S.; O'Callaghan, J.; Purvis, J. A.; Pye, M.; Senior, R.; Sutton, D. A.; Thomas, S. H. L.; Wilkinson, P. R.; Wilmott, R.; Wrigley, M. J.; Abadier, R.; Abbud, Z. A.; Adams, K. V.; Adler, S. W.; Agarwal, S.; Ahmed, A. M.; Ahmed, I. S.; Aiuto, M. A.; Albrittun, T. D.; Aliyar, P.; Allan, J. J.; Allen, D. P.; Allen, S. L.; Altschuller, A.; Amin, M.; Anand, I. S.; Antolick, A. B.; Arora, R.; Arouni, A. J.; Arslanian, C. L.; Asinger, R. W.; Aycock, G. R.; Bariciano, R. J.; Baron, S. B.; Barr, M. A.; Bartkowiak, A. J.; Baruch, L.; Basignani, C.; Bass, M. L.; Bean, B.; Bedwell, N. W.; Belber, A. D.; Belew, K.; Bell, Y. C.; Bellinger, R. L.; Bennett, W. T.; Bensimhon, D. R.; Benton, R.; Benton, R. E.; Ben-Yehuda, O.; Bertolet, B. D.; Betkowski, A. S.; Bilazarian, S. D.; Bissette, J. K.; Bobade, M. B.; Bolster, D. E.; Bomba, J.; Book, D. M.; Boscia, J. A.; Bouchard, A.; Bowman, L. M.; Bradley, A. J.; Brandt, H. D.; Bricker, C. R.; Brobyn, T. L.; Brock, R. I.; Broderick, T. M.; Broedlin, K.; Brown, A. M.; Browne, K. F.; Burke, S. W.; Burton, M. E.; Buser, G. A.; Capasso, M. K.; Caplan, W. E.; Cappelli, J.; Cardona, C.; Cardona, F.; Carlson, T.; Carr, K. W.; Casey, T.; Cashion, W. R.; Cass, D. T.; Chandrashekar, Y. S.; Changlani, M.; Chapla, P. G.; Chappell, J. H.; Chen, C.; Chen, Y.; Cho, N. R.; Cieszkowski, J. H.; Clark, D. M.; Clayton, R.; Clogston, C. W.; Cockrell, D. J.; Cohen, A. I.; Cohen, T. J.; Cole, J. F.; Conway, G.; Cook, V. R.; Cornish, A. L.; Cossu, S. F.; Costello, D. L.; Courtade, D. J.; Covelli, H. C.; Crenshaw, B. S.; Crews, L. A.; Crossley, G. H.; Culp, S. C.; Curtis, B. M.; Darrow, K.; de Raad, R. E.; DeGregorio, M.; DelNegro, A. A.; Denny, D. M.; Desai, V. S.; Deumite, N. J.; Dewey, L.; Dharawat, R. N.; Dobbs, B.; Donahue, S. M.; Downey, B.; Downing, J.; Drehobl, M. A.; Drewes, W. A.; Drucker, M. N.; Duff, R.; Duggal, M.; Dunlap, S. H.; Dunning, D. W.; DuThinh, V.; Dykstra, G. T.; East, C.; Eblaghie, M. C.; Edelstein, J.; Edmiston, W. A.; Eisen, H. J.; Eisenberg, S. J.; Ellis, J. R.; Ellison, H. S.; Ellsworth, S.; Elshahawy, M.; Emlein, G.; Entcheva, M.; Essandoh, L. K.; Estrada, A. Q.; Ewing, B.; Faillace, R. T.; Fanelli, A.; Farrell, P. W.; Farris, S. W.; Fattal, P. G.; Feigenblum, D. Y.; Feldman, G. J.; Fialkow, J. A.; Fiddler, K. M.; Fields, R. H.; Finkel, M. S.; Finn, C.; Fischell, T. A.; Fishbach, M.; Fishbein, G. J.; Fisher, M. M.; Fleischhauer, F. J.; Folk, T. G.; Folkerth, S. D.; Fortman, R. R.; Frais, M. A.; Friedman, D. C.; Fuchs, G.; Fuller, F.; Garibian, G.; Gee, F. H.; Gelernt, M. D.; Genovely, H. C.; Gerber, J. R.; Germano, J. J.; Giardina, J. J.; Gilbert, J. M.; Gillespie, E. L.; Gilman, E. M.; Gitler, B.; Givens, D. H.; Glover, R.; Gogia, H. S.; Gohn, D. C.; Goldberg, R. K.; Goldberger, J. J.; Goldscher, D. A.; Goldstein, M.; Goraya, T.; Gordon, D. F.; Gottlieb, D.; Grafner, H. L.; Graham, M.; Graves, M. W.; Graziano, M.; Greco, S. N.; Greenberg, M. L.; Greenspon, A. J.; Greer, G. S.; Griffin, D. D.; Grogan, E. W.; Groo, V. L.; Guarnieri, T.; Gupta, A.; Gupta, J.; Hack, T. C.; Hall, B.; Hallak, O.; Halpern, S. W.; Hamburg, C.; Hamroff, G. S.; Han, J.; Handel, F.; Hankins, S. R.; Hanovich, G. D.; Hanrahan, J. A.; Haque, I. U.; Hargrove, J. L.; Harnick, P. E.; Harris, J. L.; Hartley, P. A.; Haskel, E. J.; Hatch, D.; Haught, W. H.; Hearne, S.; Hearne, S. E.; Hemphill, J. A.; Henderson, D. A.; Henes, C. H.; Hengerer-Yates, T.; Hermany, P. R.; Herzog, W. R.; Hickey, K.; Hilton, T. C.; Hockstad, E. S.; Hodnett, P.; Hoffmeister, R.; Holland, J.; Hollenweger, L.; Honan, M. B.; Hoopes, D. A.; Hordes, A. R.; Hotchkiss, D. A.; Howard, M. A.; Howard, V. N.; Hulyalkar, A. R.; Hurst, P.; Hutchison, L. C.; Ingram, J.; Isakov, T.; Ison, R. K.; Israel, C. N.; Jackson, B. K.; Jackson, K. N.; Jacobson, A. K.; Jain, S.; Jarmukli, N. F.; Joffe, I.; Johnson, L. E.; Johnson, S. A.; Johnson, S. L.; Jones, A. A.; Joyce, D. B.; Judson, P. L.; Juk, S. S.; Kaatz, S.; Kaddaha, R. M.; Kaplan, K. J.; Karunaratne, H. B.; Kennett, J. D.; Kenton, D. M.; Kettunen, J. A.; Khan, M. A.; Khant, R. N.; Kirkwood, M. D.; Knight, B. P.; Knight, P. O.; Knutson, T. J.; Kobayashi, J. F.; Kogan, A.; Kogan, A. D.; Koren, M. J.; Kosinski, E. J.; Kosolcharoen, P.; Kostis, J. B.; Kramer, J. H.; Kramer, S. D.; Kron, J.; Kuchenrither, C. R.; Kulback, S. J.; Kumar, A.; Kushner, D.; Kutscher, A.; Lai, C. K.; Lam, J. B.; Landau, C.; Landzberg, J. S.; Lang, D. T.; Lang, J. M.; Lanzarotti, C. J.; Lascewski, D. L.; Lau, T. K.; Lee, J. K.; Lee, S.; Leimbach, W. N.; LePine, A. M.; Lesser, M. F.; Leuchak, S. H.; Levy, R. M.; Lewis, W. R.; Lincoln, T. L.; Lingerfelt, W. M.; Liston, M.; Liu, Z. G.; Lloret, R. L.; Lohrbauer, L.; Longoria, D. C.; Lott, B. M.; Louder, D. R.; Loukinen, K. L.; Lovell, J.; Lue, S.; Mackall, J. A.; Maletz, L.; Marlow, L.; Martin, R. C.; Matsumura, M.; McCartney, M. J.; McDuffie, D.; McGough, M. F.; McGrew, F. A.; McGuinn, Wm P.; McMillen, M. D.; McNeff, J.; McPherson, C. A.; Meengs, M. E.; Meengs, W. L.; Meholick, A. W.; Meisner, J. S.; Melucci, M. B.; Mercando, A.; Merlino, J. D.; Meymandi, S. K.; Miele, M. B.; Miller, R. H.; Miller, S. H.; Minor, S. T.; Mitchell, M. R.; Modi, M.; Mody, F. V.; Moeller, C. L.; Moloney, J. F.; Moran, J. E.; Morcos, N. C.; Morgan, A.; Mukherjee, S. K.; Mullinax, K.; Murphy, A. L.; Mustin, A. J.; Myers, G. I.; Naccarelli, G. V.; Nadar, V. K.; Nallasivan, M.; Navas, J. P.; Niazi, I. K.; Nsah, E. N.; Nunamaker, J. L.; Ochalek, T. B.; O'dea, D. J.; Ogilvie, P. D.; Olliff, B.; Omalley, A. K.; O'Neill, P. G.; Onufer, J. R.; Orchard, R. C.; Orihuela, L. A.; Ortiz, E. C.; O'Sullivan, M. T.; Padanilam, B. J.; Pandey, P.; Patel, D. V.; Patel, R. J.; Patel, V. B.; Patlola, R. R.; Pennock, G. D.; Perlman, R.; Peters, P. H.; Petrillo, A. V.; Pezzella, S.; Phillips, D.; Pierre-Louis, J. R.; Pilcher, G.; Pillai, C.; Pollock, S. G.; Pond, M. S.; Porterfield, J. K.; Presant, L.; Pressler, J.; Pribble, A. H.; Promisloff, S. D.; Pudi, K. K.; Putnam, D. L.; Quartner, J.; Quinn, J. C.; Quinnell, C. M.; Raad, G. L.; Rasmussen, L. A.; Ray, C.; Reiffel, J. A.; Reynertson, S.; Richardson, J. W.; Riley, C. P.; Rippy, J. S.; Rittelmeyer, J. T.; Roberts, D. M.; Robertson, R.; Robinson, V. J. B.; Rocco, T. A.; Rosenbaum, D.; Roth, E. M.; Rottman, J. N.; Rough, R. R.; Rubenstein, J. J.; Sakkal, A. M.; Saleem, T.; Salerno, D. M.; Samendinger, M. L.; Sandeno, S.; Santilli, T. M.; Santucci, P.; Sattar, P.; Saxman, K. A.; Schaefer, S.; Schmidt, J.; Schneider, R. M.; Schocken, D. D.; Schrader, M. K.; Schramm, B. A.; Schultz, R. W.; Schussheim, A. E.; Schwarz, E. F.; Seamon, M. C.; Sestero, J. D.; Shah, M. P.; Shah, R.; Shalaby, A.; Shanes, J. G.; Sheftel, G. L.; Sheikh, K. H.; Shein, A. B.; Shemonsky, N. K.; Shepler, A.; Sheridan, E.; Shipwash, T. M.; Shopnick, R. I.; Short, W. G.; Shoukfeh, M. F.; Sibia, R. S.; Siler, T. M.; Silva, J. A.; Simons, G. R.; Simpson, A. G.; Simpson, H. R.; Simpson, V. J.; Singh, B. N.; Singh, N.; Singh, V. N.; Sitz, C. J.; Skatrud, L.; Sklar, J.; Slotwiner, D. J.; Smith, P. F.; Smith, P. N.; Smith, R. H.; Smith, J. E.; Sodowick, B. C.; Solomon, A. J.; Soltero, E. A.; Sonel, A. F.; Sperling, R.; Spiller, C.; Spink, B. Z.; Sprinkle, L. W.; Spyropoulos, A. C.; Stamos, T. D.; Steljes, A. D.; Stillabower, M. E.; Stover, T.; Strain, J. E.; Strickland, T. L.; Suresh, D. P.; Takata, T. S.; Taylor, J. S.; Taylor, M.; Teague, S. M.; Teixeia, J. M.; Telfer, E. A.; Terry, P. S.; Terry, R. W.; Thai, H. M.; Thalin, M.; Thomas, V. N.; Thompson, C. A.; Thompson, M. A.; Thornton, J. W.; Tidman, R. E.; Toler, B. S.; Traina, M. I.; Trippi, J. A.; Ujiiye, D. L.; Usedom, J. E.; van de Graaff, E.; van de Wall, L. R.; Vaughn, J. W.; Ver Steeg, D.; Vicari, R. M.; Vijay, N.; Vitale, C. B.; Vlastaris, A. G.; Voda, J.; Vora, K. N.; Voyles, W. F.; Vranian, R. B.; Vrooman, P. S.; Waack, P.; Waldo, A. L.; Walker, J. L.; Wallace, M. A.; Walsh, E. A.; Walsh, R. L.; Walton, A.; Washam, M.; Wehner, P. S.; Wei, J. Y.; Weiner, S.; Weiss, R. J.; Wells, D. M.; Wera-Archakul, W.; Wertheimer, J. H.; West, S. A.; Whitaker, J. H.; White, M. L.; White, R. H.; Whitehill, J. N.; Wiegman, P. J.; Wiesel, J.; Williams, J.; Williams, L. E.; Williams, M. L.; Williamson, V. K.; Wilson, V. E.; Wilson, W. W.; Woodfield, S. L.; Wulff, C. W.; Yates, S. W.; Yousuf, K. A.; Zakhary, B. G.; Zambrano, R.; Zimetbaum, P.; Zoble, R.; Zopo, A. R.; Zwerner, P. L.

    2009-01-01

    BACKGROUND: Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. METHODS: In this noninferiority trial, we randomly assigned 18,113 patients who had atrial

  16. Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism

    NARCIS (Netherlands)

    Büller, Harry R.; Décousus, Hervé; Grosso, Michael A.; Mercuri, Michele; Middeldorp, Saskia; Prins, Martin H.; Raskob, Gary E.; Schellong, Sebastian M.; Schwocho, Lee; Segers, Annelise; Shi, Minggao; Verhamme, Peter; Wells, Phil; Agnelli, Giancarlo; Angchaisuksiri, Pantep; Banyai, Martin; Bauersachs, Rupert; van Bellen, Bonno; Blüguermann, Julio; Boda, Zoltán; Bounameaux, Henri; Brenner, Benjamin; Brighton, Tim; Castañon, Javier Diaz; Chechulov, Pavel; Chlumský, Yaromir; Cohen, Alexander; Davidson, Bruce; Decousus, Hervé; Eriksson, Henry; Gallus, Alexander; Gudz, Ivan; Jacobson, Barry; Heng, Lee Lai; Lyons, Roger; Meijer, Karina; Minar, Erich; Monreal, Manuel; Nakamura, Mashio; Oh, Doyeun; Öngen, Gül; Parakh, Rajiv; Piovella, Franco; Raskob, Gary; Rehm, Jeffery; Sandset, Per Morten; Schellong, Sebastian; Smith, Mark; Sokurenko, German; Tomkowski, Witold; Torp-Pedersen, Christian; Wang, Chen; Wang, Yuqi; Weitz, Jeff; Yanushko, Vyacheslav; Yin, Wei-Hsian; Prins, Martin; Beenen, Ludo; Brandjes, Dees; MacGillavry, Melvin; Kaplowitz, Neil; Otten, Hans-Martin; Pessayre, Dominique; Peters, Ron; Roos, Yvo; Slagboom, Ton; Eikelboom, John; Crowther, Mark; Roberts, Robin; Vanassche, Thomas; Vandenbriele, Christophe; Debaveye, Barbara; Dani, Viddhi; van Bergen, Petro; Gerrits, Paul; van Kranen, Robbert; Lanz, Hans; Grosso, Michael; Kappelhoff, John; Franc, John; Zhang, George; Lin, Min; Crerand, William; Giordano, Chris; Skinner, Maureen; Hurley, Steve; Lovelace, Gregg; Barrier, Robert; Betcher, Josh; Alvarez, C.; Amuchastegui, L. M.; Blüguermann, J.; Cassettari, A.; Ceressetto, J.; Hrabar, NN; Macin, S.; Mahuad, C.; Oberti, P.; Santini, F.; Baker, R. I.; Blombery, P.; Brighton, T.; Carroll, P.; Chong, B.; Coughlin, P.; Crispin, P.; Fletcher, J.; Gallus, A.; Serisier, D. J.; Tran, H.; Chan, N.; Stafford, L.; Ward, C.; Baghestanian, M.; Kyrle, P. A.; Eischer, L.; Traby, L.; Marschang, P.; Mathies, R.; Pilger, E.; Brodmann, M.; Roithinger, F.; Weltermann, A.; Adzerikho, I.; Davidovskaya, E.; Gorokhovsky, S.; Maslianski, B.; Kulik, A.; Yanushka, A.; de Vleeschauwer, P.; Debing, E.; Duchateau, J.; Gustin, M.; Hainaut, P.; Vandekerkhof, J.; Verhamme, P.; Peerlinck, K.; Verstraeten, P.; Wautrecht, J. C.; Motte, S.; Annichino-Bizzacchi, J. M.; Mello, T. B. T.; Menezes, F. H.; Burihan, M.; Cavalcanti, M.; Correa, J.; Correa de Carvalho, F.; Cukier, A.; Manenti, E.; Manenti, E. R.; Sacilotto, R.; Timi, J. M.; van Bellen, B.; Kahn, S. R.; Kovacs, M.; Langner, A. Lazo; VanSpronsen, H.; Ritchie, B.; Shafai-Sarshar, R.; Shivakumar, S.; Anderson, D.; Robinson, K.; Gallant, B.; Wells, P.; Karovitch, A.; Scarvelis, D.; Carrier, M.; Bai, C. X.; Chen, R. C.; Cheng, Z. Z.; Du, Y. C.; Hu, X. Y.; Gu, Y. Q.; Hao, Q. L.; Sun, S. B.; Wang, C.; Jiang, L.; Liu, C. J.; Liu, C. W.; Liu, S.; Wang, X. X.; Ye, X. F.; Ma, Z.; Qin, Z. Q.; Qin, X. J.; Tian, H. Y.; Wang, Y. Q.; Shi, Z. Y.; Wen, F. Q.; Wu, Q.; Yang, Y. H.; Kuang, T. G.; Yang, H.; Ying, K. J.; Ma, G. F.; Yuan, Y. D.; Yu, J.; Gong, X. W.; Zhang, F. X.; Zhang, J.; Zhang, S. X.; Zhang, J. W.; Zhang, L.; Zhao, J. C.; Huang, B.; Zhao, J.; Chlumsky, J.; Hola, D.; Hirmerova, J.; Hutyra, M.; Klimsa, Z.; Holub, M.; Kovarova, K.; Lang, P.; Ryba, M.; Podoubský, R.; Matoska, P.; Mayer, O.; Patek, F.; Tupa, M.; Spacek, R.; Urbanova, R.; Blazejova, S.; Vitovec, M.; Andersen, B.; Brønnum-Schou, J.; Dominguez, H.; Egstrup, K.; Auscher, S.; Jeppesen, J.; Asferg, C.; Vishram, J.; Nielsen, H.; Galsgaard, I.; Michaelsen, M.; Haugaard-Nielsen, B.; Ostergaard, O.; Poulsen, S. H.; Torp-Pedersen, C.; Masik, S.; Kadarik, M.; Meriste, S.; Paumets, M.; Laheäär, M.; Raidjuk, L.; Accassat, S.; Buchmuller, A.; Mismetti, P.; Achkar, A.; Aquilanti, S.; Rifaï, A.; Breuil, N.; Schmidt, J.; Brisot, D.; Brousse, C.; de la Fuentes, P. Tarodo; Chakra, M.; Crestani, B.; Desormais, I.; Lacroix, P.; Diamand, J. M.; El Kouri, D.; Clairand, R.; Elias, A.; Ferrari, E.; Doyen, D.; Chiche, O.; Grange, C.; Guenneguez, H.; Lacut, K.; Couturaud, F.; Mottier, D.; Leroux, L.; Lorcerie, B.; de Maistre, E.; Berthier, S.; Mahe, I.; Martin, M.; Meneveau, N.; Meyer, G.; Sanchez, O.; Montaclair, K.; Pavic, M.; Pernod, G.; Imbert, B.; Quere, I.; Galanaud, J. P.; Roy, P. M.; Sevestre, M. A.; Simoneau, G.; Stephan, D.; Aleil, B.; Mirea, C.; Trinh-Duc, A.; von Bilderling, P. Baron; Beyer-Westendorf, J.; Werth, S.; Köhler, C.; Halbritter, K.; Diehm, C.; Espinola-Klein, C.; Weisser, G.; Franke, D.; Heuer, H.; Horacek, T.; Kahrmann, G.; Kroening, R.; Lawall, H.; Roecken, M.; Schellong, S. M.; Pomper, L.; Voigts, B.; Bernhard, S.; Frommhold, R.; Stellbrink, C.; Boda, Z.; Ilonczai, P.; Olah, Z.; Razso, K.; Schlammadinger, A.; Farkas, K.; Kolossváry, E.; Szabó, I.; Frankfurter, Z.; Gasztonyi, B.; Gurzó, M.; Klucsik, Z.; Kovacs, A.; Szigeti, S.; Varga, C.; Landi, A.; Nyirati, G.; Pecsvarady, Zs; Riba, M.; Sámson, Z.; Sipos, Gy; Szigyártó, M.; Sebő, N.; Szabó, T. Janossikné; Toth, K.; Agarwal, S.; Arneja, J.; Babhulkar, S.; Balaji, R.; Banker, D.; Bhagavan, N. K.; Bhonagiri, S.; Mehta, A.; Dayasagar Rao, V.; Desai, P.; Desai, S. C.; Chandrashekar, A. R.; Singh, R.; Deshpande, A.; Dharmadhikari, A.; Durairaj, N.; Ghaisas, N.; Gupta, S.; Jain, R.; Jindal, R.; Kamerkar, D.; Kothiwale, V. A.; Kothurkar, A.; Kulkarni, R.; Kumar, S.; Mody, B.; Nagabhushan, K. N.; Pandharpurkar, H. K.; Joshi, S.; Parakh, R.; Grover, T.; Patel, J.; Patel, K.; Dudhagra, N.; Pawar, N.; Penurkar, M.; Pinjala, R.; Rai, K.; Rao, B.; Raval, M.; Raval, A.; Mehta, P.; Ravi Kishore, A. G.; Saravanan, S.; Shetty, P.; Srinivas, A.; Suresh, K. R.; Sumanthraj, K.; Girija, K. R.; Vinod, M. Vijan; Gavish, D.; Ashkenazy, B.; Braester, A.; Caraco, Y.; Elias, M.; Goldstein, L.; Grossman, E.; Lahav, M.; Lishner, M.; Lugassy, G.; Oliven, A.; Rachmilevitz, R.; Tzoran, I.; Brenner, B.; Yeganeh, S.; Zeltser, D.; Zimlichman, R.; Ageno, W.; Barillari, G.; Pasca, S.; Bortoluzzi, C.; Cattaneo, M.; Falanga, A.; Ghirarduzzi, A.; Lodigiani, C.; Picchi, C.; Iosub, D. I.; Porreca, E.; Prandoni, P.; Quintavalla, R.; Siragusa, S.; Akita, T.; Aoyama, T.; Fujimoto, K.; Hanzawa, K.; Ikeda, U.; Iwata, H.; Kobayashi, T.; Kondo, K.; Kurimoto, T.; Maeda, H.; Mo, M.; Munemasa, M.; Murakami, H.; Nishi, Y.; Nishibe, T.; Nishigami, K.; Nunohiro, T.; Obayashi, T.; Satoh, T.; Satokawa, H.; Shimizu, K.; Shiroma, H.; Sonoda, M.; Suzuki, Y.; Taniguchi, S.; Tsujita, K.; Yamada, N.; Yasuda, C.; Yoshida, H.; Chang, H. J.; Choi, W. I.; Kwon, K. Y.; Rho, B. H.; Choi, J. S.; Hong, Y. S.; Joh, J. H.; Kim, D. J.; Kim, H. S.; Kim, S. H.; Kim, Y. K.; Kim, K. U.; Kim, J. Y.; Kwon, T. W.; Lee, T. S.; Lim, S. Y.; Mun, Y. C.; Oh, D. Y.; Park, K. H.; Yun, W. S.; Yoon, H. I.; Diaz-Castañon, J.; Flota, L. F.; Galindo, J.; Gomez Lara, J.; Jerjes-Sanchez, C.; Palomar-Lever, A.; Rodriguez, D.; Higareda, I.; Boersma, W. G.; de Graaff, C. S.; Oudeman, L.; Brans, E.; Bredie, S. J. H.; Dees, A.; Erdkamp, F.; Peters, F.; Fijnheer, R.; Gerdes, V. E. A.; Griffioen, A.; Jie, K.-S. G.; Meijer, K.; Kooistra, H.; Wiewel-Verschueren, S.; Kamphuisen, P. W.; van Es, J.; Eerenberg, E. S.; Swart Heikens, J.; ten Cate, H.; ten Wolde, M.; Hes, R.; Atalay, S.; Harper, P.; Merriman, E.; Ockelford, P.; Hulton, M. H.; Phillips, J.; Royle, G.; Ford, A.; Smith, M.; Ghanima, W.; Amundsen, H.; Sandset, P. M.; Abola, M. T.; Ganzon, M. S.; Germar, A.; Checinski, P.; Kwasniewski, A.; Tomkowski, W.; Zechowicz, T.; Apartsin, K.; Arutyunov, G.; Barbarash, O.; Burov, Y.; Chechulov, P.; Varaksina, E.; Chernyatina, M.; Gladchenko, M.; Belikov, L.; Fokin, A.; Gubenko, A.; Igor, K.; Olga, M.; Kazakov, Y.; Kazakov, A.; Krasavin, V.; Linev, K.; Plechev, V.; Shesternya, P.; Shkurin, V.; Shvalb, P.; Sokurenko, G.; Sonkin, I.; Remizov, A.; Chernykh, K.; Staroverov, I.; Subbotin, Y.; Zeltser, M.; Seletsky, A.; Iliynykh, A.; Zilber, A.; Zubareva, N.; Tkachenko, I.; Pakhomova, A.; Raghuram, J.; Ng, H. J.; Sin, K.; Adler, D.; Weber, F.; van der Jagt, R.; Basson, M.; Becker, J.; Ellis, G.; Isaacs, R.; Jacobson, B.; Louw, S.; van Rensburg, Jansen; Siebert, H.; Skosana, F.; van Marle, J.; van Zyl, L.; le Roux, R.; Williams, P.; Cereto, F.; Garcia-Bragado, F.; Miranda, R. Tirado; Carlsson, A.; Eriksson, H.; Villegas-Scivetti, M.; Ottosson, E.; Sjalander, A.; Torstensson, I.; Banyai, M.; Afarideh, R.; Gallino, A.; Mazzolai, L.; Righini, M.; Staub, D.; Chen, C. J.; Chiang, C. E.; Wang, K. L.; Chiu, K. M.; Huang, J. H.; Lai, W. T.; Pai, P. Y.; Lin, K. H.; Wang, J. H.; Wu, C. C.; Yin, W. H.; Huang, C. L.; Angchaisuksiri, P.; Kulpraneet, M.; Rojnuckarin, P.; Öngen, G.; Duman, B.; Ozkan, S.; Savas, I.; Selçuk, T.; Tuncay, E.; Gerasymov, V.; Gubka, O.; Gudz, I.; Voloshyn, M.; Nikulnikov, P.; Danylets, A.; Prasol, V.; Rusyn, V.; Sergeev, O.; Shtutin, O.; Skupyy, O.; Tatarin, A.; Venger, I.; Cohen, A. T.; Patel, R.; Hunt, B. J.; Kesteven, P.; Robson, L.; MacCallum, P.; Nokes, T.; Rose, P.; Acs, P.; Gordan, L.; Bhatia, A.; Ali, M.; Amin, D.; Masson, J.; Gavi, E.; Ayele, E.; Ayeni, O.; Canosa, R.; Chavous, D.; Chen, D.; Comerota, A.; Concha, M.; Cunanan-Bush, M.; Daboul, N.; Daggubati, S.; Dang, N.; DiBella, N.; Driver, A.; Dulgeroff, A.; Fraiz, J.; Friedlander, A.; Galvez, A.; Jani, C.; Johnson, S.; Khandelwal, P.; Kingsley, E.; Kingsley, J.; Hutchinson, L.; Lavender, R.; Lyons, R.; Guzley, G.; Martinez, R.; Metjian, A.; Moran, J.; Nadar, V.; Pish, R.; Pullman, J.; Quaranta, A. J.; Ravi, C.; Refaai, M.; Rehm, J.; Richards, D.; Richwine, R.; Sachdeva, S.; Seibert, A.; Sharma, A.; Stricklin, D.; Tannenbaum, A.; Tin-U, C.; Vora, K.; Watkins, D.; Willms, D.

    2013-01-01

    BackgroundWhether the oral factor Xa inhibitor edoxaban can be an alternative to warfarin in patients with venous thromboembolism is unclear. MethodsIn a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received

  17. Edoxaban versus Warfarin in Patients with Atrial Fibrillation

    NARCIS (Netherlands)

    Giugliano, Robert P.; Ruff, Christian T.; Braunwald, Eugene; Murphy, Sabina A.; Wiviott, Stephen D.; Halperin, Jonathan L.; Waldo, Albert L.; Ezekowitz, Michael D.; Weitz, Jeffrey I.; Špinar, Jindřich; Ruzyllo, Witold; Ruda, Mikhail; Koretsune, Yukihiro; Betcher, Joshua; Shi, Minggao; Grip, Laura T.; Patel, Shirali P.; Patel, Indravadan; Hanyok, James J.; Mercuri, Michele; Antman, Elliott M.; Braunwald, E.; Antman, E. M.; Giugliano, R. P.; Ruff, C. T.; Morin, S. E.; Hoffman, E. B.; Murphy, S. A.; Deenadayalu, N.; Grip, L.; Mercuri, M.; Lanz, H.; Patel, I.; Curt, V.; Duggal, A.; Hanyok, J.; Davé, J.; Morgan, D.; Choi, Y.; Shi, M.; Jin, J.; Xie, J.; Crerand, W.; Kappelhof, J.; Maxwell, W.; Skinner, M.; Patel, S.; Betcher, J.; Selicato, G.; Otto, C.; Reissner, C.; Smith, K.; Ostroske, J.; Ron, A.; Connolly, S.; Camm, J.; Ezekowitz, M.; Halperin, J.; Waldo, A.; Paolasso, E.; Aylward, P.; Heidbuchel, H.; Nicolau, J. C.; Goudev, A.; Roy, D.; Weitz, J.; Corbalán, R.; Yang, Y.; Botero, R.; Bergovec, M.; Ŝpinar, J.; Grande, P.; Hassager, C.; Voitk, J.; Huikuri, H.; Nieminen, M.; Blanc, J. J.; LeHeuzey, J. Y.; Mitrovic, V.; Alexopoulos, D.; Sotomora, G.; Kiss, R.; SomaRaju, B.; Lewis, B.; Merlini, P.; Metra, M.; Koretsune, Y.; Yamashita, T.; García-Castillo, A.; Oude Ophuis, T.; White, H.; Atar, D.; Horna, M.; Babilonia, N.; Ruzyllo, W.; Morais, J.; Dorobantu, M.; Ruda, M.; Ostojic, M.; Duris, T.; Dalby, A.; Chung, N.; Zamorano, J. L.; Juul-Möller, S.; Moccetti, T.; Chen, S. A.; Sritara, P.; Oto, A.; Parkhomenko, A.; Senior, R.; Verheugt, F.; Skene, A.; Anderson, J.; Bauer, K.; Easton, J. D.; Goto, S.; Wiviott, S.; Lowe, C.; Awtry, E.; Berger, C. J.; Croce, K.; Desai, A.; Gelfand, E.; Goessling, W.; Greenberger, N. J.; Ho, C.; Leeman, D. E.; Link, M. S.; Norden, A. D.; Pande, A.; Rost, N.; Ruberg, F.; Silverman, S.; Singhal, A.; Vita, J. A.; Vogelmann, O.; Gonzalez, C.; Ahuad Guerrero, R.; Rodriguez, M.; Albisu, J.; Rosales, E.; Allall, O.; Reguero, M.; Alvarez, C.; Garcia, M.; Ameriso, S.; Ameriso, P.; Amuchastegui, M.; Caceres, M.; Beloscar, J.; Petrucci, J.; Berli, M.; Budassi, N.; Valle, M.; Bustamante Labarta, G.; Saravia, M.; Caccavo, A.; Fracaro, V.; Cartasegna, L.; Novas, V.; Caruso, O.; Zarandon, R. Saa; Colombo, H.; Morandini, M.; Cuello, J.; Rosell, M.; Cuneo, C.; Bocanera, M.; D'Amico, A.; Cendali, G.; Dran, R.; Moreno, V.; Estol, C.; Davolos, M.; Facello, A.; Facello, M.; Falu, E.; Iriarte, M.; Femenia, F.; Arrieta, M.; Fuselli, J.; Zanotti, A.; Gant Lopez, J.; Meiller, F.; Garcia Duran, R.; Perlo, D.; Garrido, M.; Ceirano, C.; Giacomi, G.; Eden, M.; Giannaula, R.; Huerta, M.; Goicoechea, R.; von Wulffen, M.; Hominal, M.; Bianchini, M.; Jure, H.; Jure, D.; Kevorkian, R.; Monaco, F.; Lanternier, G.; Belcuore, M.; Liniado, G.; Iglesias, M.; Litvak, B.; Nigro, A.; Llanos, J.; Vignau, S.; Lorente, C.; Shatsky, K.; Lotti, J.; Raimondi, G.; Mackinnon, I.; Carne, M.; Manuale, O.; Calderon, M.; Marino, J.; Funes, I.; Muntaner, J.; Gandur, H.; Nul, D.; Verdini, E.; Piskorz, D.; Tommasi, A.; Povedano, G.; Casares, E.; Pozzer, D.; Fernandez, E.; Prado, A.; Venturini, C.; Ramos, H.; Navarrete, S.; Alvarez, M.; Sanchez, A.; Bowen, L.; Sanjurjo, M.; Codutti, O.; Saravia Toledo, S.; Formoso, I.; Schmidberg, J.; Goloboulicz, A.; Schygiel, P.; Buzzetti, C.; Severino, P.; Morara, P.; Sosa Liprandi, M.; Teves, M.; Vico, M.; Morell, Y.; Anderson, C.; Paraskevaidis, T.; Arstall, M.; Hoffmann, B.; Colquhoun, D.; Price-Smith, S.; Crimmins, D.; Slattery, A.; Dart, A.; Kay, S.; Davis, S.; Silver, G.; Flecknoe-Brown, S.; Roberts, J.; Gates, P.; Jones, S.; Lehman, R.; Morrison, H.; McKeirnan, M.; Li, J.; Paul, V.; Batta, C.; Purnell, P.; Perrett, L.; Szto, G.; O'Shea, V.; Capiau, L.; Banaeian, F.; de Bleecker, J.; de Koning, K.; de Tollenaere, M.; de Bruyne, L.; Desfontaines, P.; Tincani, G.; Meeusen, K.; Herzet, J.; Malmendier, D.; Mairesse, G.; Raepers, M.; Parqué, J.; Clinckemaille, N.; Scavée, C.; Huyberechts, D.; Stockman, D.; Jacobs, C.; Vandekerckhove, Y.; Derycker, K.; Vanwelden, J.; van Welden, J.; Vervoort, G.; Mestdagh, I.; Vrolix, M.; Beerts, C.; Wollaert, B.; Denie, D.; Amato Vincenzo de Paola, A.; Coutinho, E.; Andrade Lotufo, P.; de Melo, R. Ferreira; Atie, J.; Motta, C.; Augusto Alves da Costa, F.; Ferraz, R. Franchin; Bertolim Precoma, D.; Sehnem, E.; Botelho, R.; Cunha, S.; Brondani, R.; Fleck, N.; Chaves Junior, H.; Silva, J.; Costantini, C.; Barroso, D.; de Patta, M.; Pereira, V.; Duda, N.; Laimer, R.; Dutra, O.; Morgado, S.; Faustino Saporito, W.; Seroqui, M.; Ferreira, L.; Araújo, E.; Finimundi, H.; Daitz, C.; Gagliardi, R.; Pereira, G.; Gomes, M.; Gomes, A.; Guimarães, A.; Ninho, L.; Jaeger, C.; Pereira, L.; Jorge, J.; Cury, C.; Kaiser, S.; Almeida, A.; Kalil, C.; Radaelli, G.; Kunz Sebba Barroso de Souza, W.; Morales, K.; Leaes, P.; Luiz, R. Osorio; Pimenta Almeida, J.; Gozalo, A.; Reis, G.; Avellar, K.; Reis Katz Weiand, L.; Leipelt, J.; Rocha, J.; Barros, R.; Rodrigues, L.; Rocha, M. Rubia; Rodrigues, A.; Rodrigues, D.; Rossi dos Santos, F.; Pagnan, L. Goncalves; Sampaio, R.; do Val, R.; Saraiva, J.; Vicente, C.; Simoes, M.; Carraro, A.; Sobral Filho, D.; Lustosa, E.; Villas Boas, F.; Almeida, M.; Zimmermann, S.; Zimmermann, E. Bürger; Chompalova, B.; Parishev, G.; Denchev, S.; Milcheva, N.; Donova, T.; Gergova, V.; Georgiev, B.; Kostova, E.; Kinova, E.; Hergeldjieva, V.; Kamenova, P.; Manolova, A.; Vasilev, I.; Mihov, A.; Miteva, B.; Mincheva, V.; Stoyanovski, V.; Nikolov, F.; Vasilev, D.; Pencheva, G.; Kostov, K.; Petranov, S.; Milusheva, T.; Popov, A.; Staneva, A.; Momchilova-Lozeva, D.; Todorov, G.; Nyagina, M.; Tumbev, H.; Tumbeva, D.; Tzekova, M.; Kitova, M.; Manoylov, E.; Archibald, J.; Antle, S.; Bhargava, R.; Stafford, C.; Bose, S.; Hundseth, M.; Cha, J.; Otis, J.; Chehayeb, R.; Lepage, C.; Chilvers, M.; Vansickle, L.; Cleveland, D.; Valley, S.; Constance, C.; Gauthier, M.; Costi, P.; Masson, C.; Coutu, B.; Denis, I.; Du Preez, M.; Kubanska, A.; Dufresne, M.; Krider, J.; Eikelboom, J.; Zondag, M.; Fortin, C.; Viau, C.; Green, M.; Houbraken, D.; Hatheway, R.; Mabee, J.; Heath, J.; Scott, L.; Ho, K.; Ho, V.; Hoag, G.; Standring, R.; Huynh, T.; Perkins, L.; Kouz, S.; Roy, M.; Labonte, R.; Dewar, C.; Lainesse, A.; St-Germain, L.; Lam, S.; Lam, H.; Lichtenstein, T.; Roberts, P.; Luton, R.; Douglas, S.; Ma, P.; Seib, M.; MacCallum, C.; Matthews, J.; Malette, P.; Vaillancourt, T.; Maranda, C.; Studenikow, E.; Mawji, A.; Morely, A.; Morrison, D.; Roth, M.; Mucha, M.; Najarali, A.; Lamoureux, U.; Nicholson, R.; O'Hara, G.; Banville, P.; O'Mahony, W.; Bolton, R.; Parkash, R.; Carroll, L.; Pesant, Y.; Sardin, V.; Polasek, P.; Turri, L.; Qureshi, A.; Nethercott, C.; Ricci, J.; Bozek, B.; Rupka, D.; Marchand, C.; Shu, D.; Silverio, G.; St-Hilaire, R.; Morissette, A.; Sussman, J.; Kailey, P.; Syan, G.; Bobbie, C.; Talajic, M.; David, D.; Talbot, P.; Tremblay, M.; Teitelbaum, I.; Teitelbaum, J.; Velthuysen, G.; Giesbrecht, L.; Wahby, R.; Morley, A.; Wharton, S.; Caterini, T.; Woodford, T.; Balboa, W.; Matus, L. Retamal; Bugueño, C.; Mondaca, P. Mondaca; Cobos, J.; Obreque, C.; Corbalan, R.; Parada, A.; Florenzano, F.; Diaz, P. Arratia; Lopetegui, M.; Rebolledo, C.; Manriquez, L.; Silva, L. Manríquez; Martinez, D.; Llamas, R. Romero; Opazo, M.; Pérez, M. Carmona; Pincetti, C.; Carrasco, G. Torres; Potthoff, S.; Staub, J. Zapata; Campisto, Y.; Stockins, B.; Lara, C. Lara; Yovaniniz, P.; Azua, M. Grandon; Bai, F.; Xu, G. L.; Chen, J. Z.; Xie, X. D.; Chen, X. P.; Zhang, X.; Dong, Y. G.; Feng, C.; Fu, G. S.; Zhang, P.; Hong, K.; You, Z. G.; Hong, L.; Qiu, Y.; Jiang, X. J.; Qu, Z.; Li, L.; Liu, H.; Li, T. F.; Kong, Y. Q.; Li, W. M.; Liu, B.; Li, Z. Q.; Liu, Y.; Liao, D. N.; Gu, X. J.; Liu, L.; Lu, Z. H.; Ma, S. M.; Yang, Z. Y.; Wang, D. M.; Qi, S. Y.; Wang, G. P.; Shi, X. J.; Wei, M.; Huang, D.; Wu, S. L.; Li, Y. E.; Xu, J. H.; Gu, J. Y.; Xu, Y. M.; Liang, Y. Z.; Yang, K.; Li, A. Y.; Yang, Y. J.; Zheng, X.; Zheng, Y.; Gao, M.; Yin, Y. H.; Xu, Y. P.; Yu, B.; Li, L. L.; Yuan, Z. Y.; Qiang, H.; Zhang, H. Q.; Lin, Y. N.; Zhang, Z.; Kang, H.; Zhao, R. P.; Han, R. J.; Zhao, X. L.; Wang, J. Q.; Zheng, Z. Q.; Li, B. G.; Zhou, S. X.; Zhang, Y. L.; Accini, J.; Accini, M.; Cano, N.; Pineda, L. León; Delgado Restrepo, J.; Arroyave, C.; Fernández Ruiz, R.; Diaz, I. Aldana; Hernandez, H.; Delgado, P.; Jaramillo Muñoz, C.; Builes, A.; Manzur, F.; Rodriguez, E. Rivera; Moncada Corredor, M.; Giraldo, D. Lopez; Orozco Linares, L.; Fonseca, J.; Quintero, A.; Gonzales, C.; Sanchez Vallejo, G.; Mejia, I. Perdomo; Bagatin, J.; Carevic, V.; Car, S.; Jeric, M.; Ciglenecki, N.; Tusek, S.; Ferri Certic, J.; Romic, I.; Francetic, I.; Ausperger, K. Makar; Jelic, V.; Jurinjak, S. Jaksic; Knezevic, A.; Buksa, B.; Samardzic, P.; Lukenda, K. Cvitkusic; Steiner, R.; Kirner, D.; Sutalo, K.; Bakliza, Z.; Vrazic, H.; Lucijanic, T.; Bar, M.; Brodova, P.; Berka, L.; Kunkelova, V.; Brtko, M.; Burianova, H.; Cermak, O.; Elbl, L.; Ferkl, R.; Florian, J.; Francek, L.; Golan, L.; Gregor, P.; Honkova, M.; Hubac, J.; Jandik, J.; Jarkovsky, P.; Jelinek, Z.; Jerabek, O.; Jirmar, R.; Kobza, R.; Kochrt, M.; Kostkova, G.; Kosek, Z.; Kovar, P.; Kuchar, R.; Kvasnicka, J.; Ludka, O.; Machova, V.; Krocova, E.; Melichar, M.; Nechanicky, R.; Olsr, J.; Peterka, K.; Petrova, I.; Havlova, I.; Pisova, J.; Podrazil, P.; Jirsova, E.; Reichert, P.; Slaby, J.; Spacek, R.; Spinar, J.; Labrova, R.; Vodnansky, P.; Samkova, D.; Zidkova, E.; Dodt, K.; Christensen, H.; Christensen, L.; Loof, A.; Ibsen, H.; Madsen, H.; Iversen, H.; Veng-Olsen, T.; Nielsen, H.; Olsen, R.; Overgaard, K.; Petrovic, V.; Raymond, I.; Raae, D.; Sand, N.; Svenningsen, A.; Torp-Pedersen, C.; Jakobsen, U.; Wiggers, H.; Serup-Hansen, K.; Kaik, J.; Stern, A.; Kolk, R.; Laane, E.; Rivis, L.; Paumets, M.; Laheäär, M.; Rosenthal, A.; Rajasalu, R.; Vahula, V.; Ratnik, E.; Kaarleenkaski, S.; Hussi, E.; Valpas, S.; Jäkälä, P.; Lappalainen, T.; Mäenpää, A.; Viitaniemi, J.; Nyman, K.; Sankari, T.; Rasi, H.; Salminen, O.; Virtanen, V.; Nappila, H.; Le Heuzey, J.; Agraou, B.; El Jarroudi, F.; Amarenco, P.; Boursin, P.; Babuty, D.; Boyer, M.; Belhassane, A.; Berbari, H.; Blanc, J.; Dias, P.; Coisne, D.; Berger, N.; Decoulx, E.; El Jarroudi, M.; Dinanian, S.; Arfaoui, M.; Hermida, J.; Deruche, E.; Kacet, S.; Corbut, S.; Poulard, J.; Leparree, S.; Roudaut, R.; Duprat, C.; Al-Zoebi, A.; Wurow, A.; Bernhardt, P.; Dichristin, U.; Berrouschot, J.; Vierbeck, S.; Beyer-Westendorf, J.; Sehr, B.; Bouzo, M.; Schnelzer, P.; Braun, R.; Ladenburger, K.; Buhr, M.; Weihrauch, D.; Contzen, C.; Kara, M.; Daut, W.; Ayasse, D.; Degtyareva, E.; Kranz, P.; Drescher, T.; Herfurth, B.; Faghih, M.; Forck-Boedeker, K.; Schneider, K.; Fuchs, R.; Manuela, W.; Grigat, C.; Otto, A.; Hartmann, A.; Peitz, M.; Heuer, H.; Dieckheuer, U.; Hoffmann, U.; Dorn, S.; Hoffmann, S.; Schuppe, M.; Horacek, T.; Fink, P.; Junggeburth, J.; Schmid, S.; Jungmair, W.; Schoen, B.; Kleinecke-Pohl, U.; Meusel, P.; Koenig, H.; Bauch, F.; Lohrbaecher-Kozak, I.; Grosse, B.; Lueders, S.; Venneklaas, U.; Luttermann, M.; Wulf, M.; Maus, O.; Hoefer, K.; Meissner, G.; Braemer, U.; Meyer-Pannwitt, U.; Frahm, E.; Vogt, S.; Muegge, A.; Barbera, S.; Mueller-Glamann, M.; Raddatz, K.; Piechatzek, R.; Lewinsky, D.; Pohl, W.; Proskynitopoulos, N.; Kuhlmann, M.; Rack, K.; Pilipenko, H.; Rinke, A.; Kühlenborg, A.; Schaefer, A.; Szymanowski, N.; Schellong, S.; Frommhold, R.; Schenkenberger, I.; Finsterbusch, T.; Dreykluft, K.; Schiewe, C.; Schmidt, A.; Schmidt, M.; Schreckenberg, A.; Hellmers, J.; Seibert, H.; Gold, G.; Sohn, H.; Baylacher, M.; Spitzer, S.; Bonin, K.; Stoehring, R.; Taggeselle, J.; Zarpentin, C.; Veltkamp, R.; Ludwig, I.; Voehringer, N. N.; Buchholz, M.; Weyland, K.; Winkelmann, B.; Buelow-Johansen, B.; Wolde, C.; Winter, K.; Mavronasiou, E.; Bourlios, P.; Tziortziotis, A.; Karamitsos, C.; Exarchou, E.; Kifnidis, K.; Daskalaki, A.; Moschos, N.; Dimitra, K.; Olympios, C.; Kartsagkoulis, E.; Pyrgakis, V.; Korantanis, K.; Ayau Milla, O.; Ramirez, V. de Leon; Guzman Melgar, I.; Jimenez, T.; Ovando Lavagnino, A.; Guevara, S.; Rodas Estrada, M.; Sanchez, M.; Pozuelos, J. Mayen; Sanchez Samayoa, C.; Guerra, L.; Velasquez Camas, L.; Almaraz, S. Padilla; Dioszeghy, P.; Muskoczki, E.; Edes, I.; Szatmari, J.; Fiok, J.; Varga, A.; Kanakaridisz, N.; Kosztyu, M.; Kis, E.; Feil, J. Felfoldine; Jakal, A.; Koczka, M.; Kovacs, I.; Baranyai, M.; Kovacs, Z.; Lupkovics, G.; Karakai, H. Horvathne; Matoltsy, A.; Kiss, T.; Medvegy, M.; Kiss, K.; Merkely, B.; Kolumban, E.; Nagy, A.; Palinkas, A.; Toth, S. Rostasne; Sayour, A.; Bognar, A.; Simor, T.; Ruzsa, D.; Sipos, T.; Szakal, I.; Tomcsanyi, J.; Marosi, A.; Vertes, A.; Kincses, M.; Malhan, S.; Abdullakutty, J.; Agarwal, D.; Ranka, R.; Arneja, J.; Memon, A.; Arora, V.; Shree, R.; Avvaru, G.; Shaikh, A.; Babu, P.; Rao, B.; Babu, R.; Reddy, J.; Banker, D.; Sheth, T.; Benjarge, P.; Surushe, S.; Bharani, A.; Solanki, R.; Bhargava, V.; Rathi, A.; Biniwale, A.; Bhuti, M.; Calambur, N.; Karnwal, N.; Chopda, M.; Mali, N.; Goyal, N.; Saini, A.; Gupta, J.; Singh, P.; Hadan, S.; Savanth, P.; Hardas, S.; Thakor, G.; Hiremath, J.; Ghume, A.; Jain, R.; Pahuja, M.; Joseph, S.; Oommen, D.; Joseph, J.; Thomas, R.; Joshi, H.; Iby, N. N.; Kale, V.; Raut, N.; Kandekar, B.; Kandekar, S.; Kishore, R.; Krishnan, H.; Kotiwale, V.; Kulkarni, R.; Deokar, M.; Kulkarni, G.; Lawande, A.; Kumar, P.; Karpuram, M.; Kumar, A.; Francis, J.; Kumbla, M.; Anthony, A.; Lavhe, P.; Kale, M.; Mardikar, H.; Bhaskarwar, P.; Mathur, A.; Sharma, P.; Menon, J.; Francis, V.; Namjoshi, D.; Shelke, S.; Narendra, J.; Natarajan, S.; Oomaan, A.; Gurusamy, P.; Angel, J.; Purayil, M. Padinhare; Shams, S.; Pandurangi, U.; Sababathi, R.; Parekh, P.; Jasani, B.; Patki, N.; Babbar, A.; Pinto, B.; Kharalkar, H.; Premchand, R.; Jambula, H.; Rao, M.; Vuriya, A.; Ravi Shankar, A.; Reddy, R.; Bekal, S.; Barai, A.; Saha, D.; Gadepalli, R.; Sant, H.; Jadhav, D.; Sarna, M.; Arora, T.; Sawhney, J.; Singh, R.; Sethi, K.; Bansal, N.; Sethia, A.; Sethia, S.; Shetty, G.; Sudheer, R.; Singh, G.; Gupta, R.; Srinivas, A.; Thankaraj, L.; Varma, S.; Kaur, A.; Vinod, M. Vijan; Thakur, B.; Zanwar, I.; Dharmarao, A.; Atar, S.; Lasri, E.; Dicker, D.; Marcoviciu, D.; Elias, M.; Ron, G. Avraham; Francis, A.; Ghantous, R.; Goldhaber, A.; Goldhaber, M.; Gottlieb, S.; Rouwaida, S.; Grossman, E.; Dagan, T.; Hasin, Y.; Roshrosh, M.; Hayek, T.; Majdoub, A.; Klainman, E.; Genin, I.; Lahav, M.; Gilat, T.; Ben Ari, M.; Lishner, M.; Karny, M.; Ouzan, E.; Givoni, H.; Rozenman, Y.; Logvinenko, S.; Schiff, E.; Sterlin, J.; Shochat, M.; Aloni, I.; Swissa, M.; Belatsky, V.; Tsalihin, D.; Kisos, D.; Zeltser, D.; Platner, N.; Berni, A.; Giovannelli, F.; Boriani, G.; Cervi, E.; Comi, G.; Peruzzotti, L.; Cuccia, C.; Forgione, C.; de Caterina, R.; de Pace, D.; de Servi, S.; Mariani, M.; Di Lenarda, A.; Mazzone, C.; Di Pasquale, G.; Di Niro, M.; Fattore, L.; Bosco, B.; Grassia, V.; Murena, E.; Laffi, N. N.; Gaggioli, G.; Lo Pinto, G.; Raggi, F.; Marino, P.; Francalacci, G.; Babbolin, M.; Bulgari, M.; Penco, M.; Lioy, E.; Perrone Filardi, P.; Marciano, C.; Pirelli, S.; Paradiso, G.; Piseddu, G.; Fenu, L.; Raisaro, A.; Granzow, K.; Rasura, M.; Cannoni, S.; Severi, S.; Breschi, M.; Toschi, V.; Gagliano, M.; Zacà, V.; Furiozzi, F.; Hirahara, T.; Akihisa, U.; Masaki, W.; Ajioka, M.; Matsushita, C.; Anzai, T.; Mino, K.; Arakawa, S.; Tsukimine, A.; Endo, H.; Fujiwara, M.; Fujii, K.; Kozeni, S.; Fujii, E.; Kotera, M.; Fujimoto, S.; Omae, K.; Fujimoto, K.; Ichishita, Y.; Fujita, T.; Ito, Y.; Fukamizu, S.; Harada, J.; Fukuda, N.; Fujimoto, C.; Funazaki, T.; Yamaguchi, A.; Furukawa, Y.; Kamitake, C.; Hagiwara, N.; Naganuma, M.; Hara, S.; Kumagai, S.; Harada, K.; Fuki, Y.; Haruna, T.; Nakahara, Y.; Hashimoto, Y.; Shimazu, Y.; Hiasa, Y.; Oga, Y.; Higashikata, T.; Nakagawa, Y.; Hirayama, A.; Kawaguchi, A.; Iesaka, Y.; Miyamoto, C.; Iijima, T.; Higuchi, K.; Ino, H.; Noguchi, H.; Inomata, T.; Nakamura, K.; Ishibashi, Y.; Nozaki, T.; Ishii, Y.; Tomita, H.; Ishimaru, S.; Ise, M.; Itamoto, K.; Ito, T.; Onishi, M.; Iwade, K.; Sakuma, Y.; Iwasaki, T.; Nagatome, H.; Kakinoki, S.; Adachi, C.; Kamakura, S.; Nakahara, F.; Kamijo, M.; Iida, S.; Kamiyama, K.; Fujii, R.; Kato, K.; Ishida, A.; Kazatani, Y.; Ichikawa, Y.; Kitazawa, H.; Igarashi, C.; Kobayashi, Y.; Kikuchi, R.; Kohno, M.; Tamura, S.; Yumoto, I.; Kurabayashi, M.; Koya, E.; Masuyama, T.; Kaneno, Y.; Matsuda, K.; Ebina, E.; Meno, H.; Satake, M.; Mita, T.; Takeda, M.; Miyamoto, N.; Kimizu, T.; Miyauchi, Y.; Sakamoto, S.; Munemasa, M.; Murata, J.; Nagai, Y.; Sakata, Y.; Naito, S.; Oyama, H.; Nishi, Y.; Nagase, T.; Ochiai, J.; Junko, H.; Ogawa, T.; Sugeno, M.; Oguro, H.; Tanabe, M.; Okada, K.; Moriyama, Y.; Okajima, K.; Nakashima, M.; Okazaki, O.; Wada, H.; Okishige, K.; Kitani, S.; Okumura, K.; Narita, Y.; Onaka, H.; Moriyama, H.; Ozaki, Y.; Tanikawa, I.; Sakagami, S.; Nakano, A.; Sakuragi, S.; Hayashi, N.; Sakurai, S.; Ooki, H.; Sasaki, T.; Oosawa, N.; Satoh, A.; Fujimoto, E.; Seino, Y.; Narumi, M.; Shirai, T.; Shigenari, M.; Shoji, Y.; Ueda, J.; Sugi, K.; Miyazaki, E.; Sumii, K.; Asakura, H.; Takagi, M.; Mohri, S.; Takahashi, W.; Yoshida, K.; Takahashi, A.; Kishi, N.; Takahashi, T.; Sakurai, Y.; Takeda, K.; Yahata, A.; Takenaka, T.; Yamagishi, K.; Takeuchi, S.; Watanabe, E.; Tanaka, K.; Uchida, M.; Tanouchi, J.; Nishiya, Y.; Tsuboi, H.; Tsuboi, N.; Terakura, K.; Uematsu, M.; Yasumoto, S.; Ueyama, Y.; Usuda, K.; Sakai, Y.; Yagi, M.; Sato, A.; Yagi, H.; Kuroda, T.; Yamabe, H.; Sakamoto, Y.; Yamada, T.; Yamano, R.; Yamagishi, T.; Sasaki, S.; Yamamoto, Y.; Yamashina, A.; Takiguchi, M.; Yonehara, T.; Yoshino, H.; Nomura, H.; Yoshioka, K.; Fujiwara, Y.; Bayram Llamas, E.; Hurtado, A.; Calvo Vargas, C.; Limon, M. Cedano; Cardona Muñoz, E.; Hernandez, S.; Carrillo, J.; Delgadillo, T.; Cásares Ramirez, M.; Valles, J. Franco; Garcia, N.; Colin, M. Alcantara; Garcia-Castillo, A.; Jaramillo, A.; Leiva-Pons, J.; de la Mora, S.; Llamas Esperón, G.; Grajales, A.; Mendez-Machado, G.; Avila, H.; Ruiz, L. Nevárez; Magallanes, G.; Sánchez Díaz, C.; Ortiz, A.; Sánchez, R. Velasco; Velazquez, E. Moran; Alhakim, M.; van Welsen, I.; Bruning, T.; Jones, A.; Buiks, C.; de Groot, J. [=Joris R.; Radder, I.; de Vos, R.; Hazeleger, R.; Daniels, R.; Kietselaer, B.; Muijs, L.; Mannaerts, H.; Kooiman, E.; Mevissen, H.; van der Heijden, D.; Hofmeyer, H.; Anscombe, R.; O'Meeghan, T.; Kjentjes, M.; Benatar, J.; Borthwick, L.; Doughty, R.; Copley, M.; Fisher, R.; Monkley, R.; Green, B.; Scott, D.; Hamer, A.; Tomlinson, J.; Hart, H.; Turner, A.; Cammell, R.; Troughton, R.; Skelton, L.; Young, C.; Kennett, K.; Claussen, H.; Hofsøy, K.; Melbue, R.; Sandvik, J.; Thunhaug, H.; Tveit, A.; Enger, S.; Bustamante, G.; Guillen, M. Tejada; Cabrera, J.; Mendoza, R. Esteves; Chavez, C.; Luna, C.; Lema, J.; Carrion, A.; Llerena, N.; Bedregal, S. Araoz; Medina Palomino, F.; Rodriguez, J.; Minchola, J.; Bautista, C.; Negron Miguel, S.; Armas, B. Honores; Rodriguez, A.; Romero, N.; Torres, P.; Rodriguez, K. Fernandez; Yanac Chavez, P.; Delgado, S.; Sambaz, C. M.; Barcinas, R.; Zapanta, M.; Coching, R.; Vallenas, M.; Matiga, G.; Enad, C.; Rogelio, G.; Joaquin, F.; Roxas, A.; Gilo, L.; To, R.; Aquino, M.; Villamor, L.; Nario, K.; Adamus, J.; Korzeniowska-Adamus, J.; Baszak, J.; Bronisz, M.; Cieslak, B.; Busz-Papiez, B.; Krzystolik, A.; Cymerman, K.; Dabrowska, M.; Ptak, A.; Derlaga, B.; Laskowska-Derlaga, E.; Domanska, E.; Guziewicz, M.; Gieroba, A.; Zajac, E.; Gniot, J.; Mroczkowski, P.; Januszewicz, A.; Makowiecka-Ciesla, M.; Jazwinska-Tarnawska, E.; Ciezak, P.; Jurowiecki, J.; Kaczmarek, B.; Pacholska, A.; Kaminski, L.; Kania, G.; Tymendorf, K.; Karczmarczyk, A.; Kaliszczak, R.; Konieczny, M.; Benicka, E.; Korzeniak, R.; Borowski, W.; Krzyzanowski, W.; Muzyk-Osikowicz, M.; Kus, W.; Lesnik, J.; Wierzykowski, T.; Lewczuk, J.; Stopyra-Poczatek, M.; Lubinski, A.; Szymanska, K.; Lysek, R.; Jaguszewska, G.; Matyszczak-Toniak, L.; Sznajder, R.; Wnetrzak-Michalska, R.; Kosmaczewska, A.; Mazur, S.; Chmielowski, A.; Miekus, P.; Kosmalska, K.; Mosiewicz, J.; Myslinski, W.; Napora, P.; Biniek, D.; Nessler, J.; Nessler, B.; Niezgoda, K.; Nej, A.; Nowak, J.; Olszewski, M.; Podjacka, D.; Janczewska, D.; Pogorzelska, H.; Polaszewska-Pulkownik, V.; Bojanowska, E.; Raczak, G.; Zienciuk-Krajka, A.; Rewinska, H.; Rozmyslowicz-Szerminska, W.; Ronkowski, R.; Norwa-Otto, B.; Sendrowski, D.; Spyra, J.; Szolkiewicz, M.; Malanska, A.; Turbak, R.; Wrobel, W.; Muzalewski, P.; Wysokinski, A.; Kudlicki, J.; Zarebinski, M.; Krauze, R.; Zielinski, M.; Nawrot, M.; Matias, F.; Correia, J.; Gil, V.; Lopes, S.; Madeira, J.; Maymone, D.; Martins, D.; Neves, E.; Monteiro, P.; Oliveira, D.; Marques, A. Leitao; Castro, C.; Salgado, A.; Gonçalves, A.; Sao Marcos, H.; Santos, O.; Nunes, L. Veiga Pais; Sao Teotonio, H.; Santos, J.; Soares, D.; Albulescu, P.; Ciortea, M.; Apetrei, E.; Matei, C.; Bartos, D.; Badila, E.; Bengus, C.; Ochean, V.; Bobescu, E.; Doka, B.; Bolohan, F.; Ciobotaru, G.; Andor, M.; Coman, I.; Ghionea, M.; Constantinescu, M.; Creteanu, M.; Parasteac, M.; Cristea, M.; Anciu, M.; Crisu, D.; Jemna, D.; Dobre, I.; Voicu, O.; Dobreanu, D.; Sirbu, I.; Dragomir, D.; Jurca, S.; Iosipescu, L.; Costache, L.; Minescu, B.; Serban, D.; Pop, C.; Cozma, M.; Popescu, M.; Ardelean, A.; Sipciu, D.; Plosca, P.; Stamate, S.; Spinu, C.; Topolnitchi, L.; Topolnitchi, O.; Tudoran, M.; Tudoran, C.; Zhukova, N.; Arutyunov, G.; Chernyavskaya, T.; Ballyuzek, M.; Alexandrova, L.; Barbarash, O.; Bashkireva, A.; Bart, B.; Larina, V.; Belenky, D.; Kosolapov, Y.; Berns, S.; Yukhno, E.; Bokarev, I.; Khlevchuk, T.; Chumakova, G.; Pokutneva, O.; Demko, A.; Masin, A.; Dovgalevsky, P.; Puchinyan, N.; Drapkina, O.; Zyatenkova, E.; Egorova, L.; Esip, V.; Kirichek, N.; Filatov, A.; Soin, I.; Gilinskaya, O.; Valuyshkih, E.; Glezer, M.; Valovyeva, S.; Golitsyn, S.; Kratskina, T.; Goloshchekin, B.; Laptev, I.; Gratsiansky, N.; Mazovets, O.; Karpov, Y.; Buza, V.; Kosenko, B.; Khirmanov, V.; Kireenkov, I.; Khokhlov, A.; Sinitsina, O.; Khokhlov, R.; Tsareva, E.; Khrustalev, O.; Khrustalev, A.; Kostenko, V.; Karabalieva, S.; Koziolova, N.; Polyanskaya, E.; Kozyrev, O.; Kostenko, O.; Kuznetsov, V.; Rychkov, A.; Lavrova, O.; Tereschenko, L.; Levashov, S.; Volkova, E.; Libis, R.; Maslova, A.; Libov, I.; Moiseeva, Y.; Lila, A.; Belousova, L.; Lukyanov, Y.; Lamden, D.; Nikolaev, K.; Nikolaev, A.; Nikolskaya, I.; Khromova, O.; Novikova, N.; Patrusheva, S.; Panchenko, E.; Laguta, P.; Panov, A.; Nilk, R.; Polkanova, E.; Matveeva, I.; Poluyanova, N.; Pikalova, N.; Raskina, T.; Letaeva, M.; Rebrov, A.; Karoli, N.; Repin, M.; Rodina, N.; Shaposhnik, I.; Lebedev, E.; Shogenov, Z.; Agirov, M.; Sidorenko, B.; Vorontsova, S.; Sinitsina, I.; Orlov, V.; Golshmid, M.; Sizova, Z.; Lapidus, N.; Sobolev, K.; Erofeeva, S.; Suprun, E.; Dronov, D.; Tarasov, N.; Isakov, L.; Tereshenko, S.; Kositsyna, I.; Tikhonova, E.; Solovyev, A.; Timofeev, A.; Bulygin, S.; Ustyugov, S.; Rossovskaya, M.; Vishnevsky, A.; Kirgizova, A.; Volkov, D.; Yakusevich, V.; Petrochenko, A.; Yakushin, S.; Nikulina, N.; Zateyshchikov, D.; Zotova, I.; Zateyshchikova, A.; Mankhaeva, B.; Zenin, S.; Kononenko, O.; Zubeeva, G.; Motylev, I.; Apostolovic, S.; Djordjevic-Radojkovic, D.; Celic, V.; Majstorovic, A.; Cemerlic Adjic, N.; Bjelobrk, M.; Despotovic, N.; Erceg, P.; Ilic, S.; Ilic, B.; Krotin, M.; Djokovic, A.; Miloradovic, V.; Djokic, I.; Otasevic, P.; Tasic, N.; Potpara, T.; Polovina, M.; Putnikovic, B.; Kalezic, T.; Seferovic, P.; Milinkovic, I.; Tavciovski, D.; Davicevic, Z.; Vasiljevic-Pokrajcic, Z.; Mitrovic, P.; Vujisic Tesic, B.; Tesic, M.; Ambrovicova, V.; Ambrovic, I.; Banikova, A.; Dukat, A.; Kosmalova, V.; Dulkova, K.; Dulka, T.; Vankova, L.; Dzupina, A.; Dzupinova, M.; Hatalova, K.; Hatala, R.; Hranai, M.; Hofmanova, J.; Kasperova, V.; Reptova, A.; Mazur, J.; Pella, D.; Fedacko, J.; Ruffini, L.; Morsky, J.; Slanina, M.; Kmec, J.; Zachar, A.; Kokles, M.; Zareczky, P.; Bollova, D.; Badenhorst, J.; Erasmus, L.; Basson, M.; Poynton, M.; Allman, J.; Ellis, G.; Botha, L.; Engelbrecht, J.; Mostert, M.; Essop, M.; Nunkoo, T.; Gani, M.; Wilson, L.; Kelfkens, Y.; Mitha, I.; Taljaard, J.; Naidoo, D.; Duki, Y.; Snyders, F.; Munnik, M.; Soma, P.; Johnston, H.; van der Merwe, N.; Goosen, Y.; van Zyl, L.; le Roux, M.; Venter, T.; Wessels, L.; Bae, H. J.; Han, M. G.; Cha, J. K.; Kim, D. H.; Cho, B. R.; Ryu, D. R.; Choi, H. H.; Hong, K. S.; Chung, W. S.; Oh, Y. S.; Han, S. H.; Lee, K. H.; Hong, T. J.; Lee, H. W.; Hyon, M. S.; Jung, J. W.; Jeon, H. K.; Lee, J. M.; Kang, D. H.; Choi, K. J.; Kim, C. J.; Jin, E. S.; Kim, D. S.; Seo, J. S.; Kim, H. S.; Cha, M. J.; Kim, J. T.; Park, M. S.; Kim, J. H.; Park, J. H.; Kim, J. S.; Park, S. J.; Kim, S. H.; Seo, J. B.; Kim, Y. J.; Chun, M. Y.; Lee, M. H.; Joung, B. Y.; Lee, S. H.; Shin, D. G.; Namgung, J.; Kwak, J. J.; Rha, S. W.; Na, J. O.; Rim, S. J.; Kim, J. Y.; Arcocha Torres, M.; Rey, A. Manzanal; Blanco Coronado, J.; Puertas, I.; Bruguera Cortada, J.; Cabero, P.; Calvo, C.; Calvo, G.; de Arce Borda, A.; Asensio, A.; Diez Tejedor, E.; Guevara, M. Pérez; Gonzalez Juanatey, J.; Moure, M.; Hernandez Madrid, A.; Delgado, A.; Lopez Garcia-Aranda, V.; Barquero, R.; Manzano, L.; Abril, S. Blanco; Merino, J.; Diaz-Pintado, M.; Arias, J.; Fernandez, M.; Alvarez, R. Fernandez; Terns, M.; Delgado, M. Dachs; Villuendas, R.; Astier, L.; Appelros, P.; Åkerberg, A.; Blom, K. Berndtsson; Andersson, R.; Blomström, P.; Persson, L.; Carlsson, T.; Bengtsson, A. Stener; Dettmann, S.; Östberg, S.; Engdahl, J.; Karlsson, L.; Herlitz, J.; Winberg, L.; Jernhed, H.; Koskinen, P.; Håkansson, E.; Kozak, P.; Edlund, M.; Malmqvist, L.; Eriksson, G.; Randers, F.; Moodh, J.; Rautio, A.; Johansson, M.; Rönn, F.; Sundholm, C.; Stenberg, A.; Gunnarsson, A.; Thulin, J.; Broberg, M.; Slater, I. Petrova; Cheng, C. C.; Wu, W. S.; Chiang, C. E.; Yu, W. C.; Chiang, F. T.; Wu, Y. W.; Chiou, C. W.; Yeh, T. C.; Hsia, C. H.; Chen, Y. P.; Huang, J. L.; Chen, Y. F.; Kuo, C. T.; Wang, C. L.; Lai, W. T.; Lin, T. H.; Lee, J. T.; Pai, P. Y.; Lin, K. H.; Shyu, K. G.; Chiu, C. Z.; Tseng, W. K.; Pan, Y. F.; Ueng, K. C.; Lee, S. C.; Wang, J. H.; Tsai, W. C.; Yeh, H. I.; Kuo, J. Y.; Jirasirirojanakorn, K.; Pornchaiyasit, K.; Kaewsuwanna, P.; Sinthusopa, W.; Kiatchoosakun, S.; Sriprasert, S.; Laothavorn, P.; Bamrungpong, P.; Piyayotai, D.; Sripracha, A.; Panpunuan, P.; Sukonthasarn, A.; Mekara, W.; Vorasettakarnkij, Y.; Puripun, E.; Acikel, M.; Akilli, H.; Demir, H.; Ata, N.; Bayata, S.; Cakmak, N.; Calik, A.; Cayli, M.; Ceyhan, C.; Erdogan, D.; Ermis, C.; Kabul, K.; Kanadasi, M.; Turgut, O.; Tandogan, I.; Yalcin, R.; Yigit, F.; Yigit, Z.; Zoghi, M.; Batushkin, V.; Azhdari, M.; Bazylevych, A.; Vlasyuk, Z.; Bereznyakov, I.; Lebedynskaya, M.; Dotsenko, S.; Kulynych, R.; Dzyak, G.; Vasilyeva, L.; Faynyk, A.; Sorokivskyy, M.; Gavrysyuk, V.; Dzublik, Y.; Horbach, L.; Husyev, V.; Godlevska, O.; Samburg, Y.; Karpenko, O.; Nevolina, I.; Karpenko, Y.; Blihar, O.; Kaydashev, I.; Gerasimenko, N.; Kolomyyits, S.; Vasylets, V.; Kopytsya, M.; Petyunina, O.; Kotseruba, V.; Dvoieglazova, M.; Koval, V.; Ohirko, O.; Koval', O.; Kaplan, P.; Kraiz, I.; Usan, N.; Kraydashenko, O.; Stets, R.; Kupnovytska, I.; Kyyak, Y.; Lizogub, V.; Gorna, O.; Malynovsky, Y.; Fedotov, S.; Ostrovska, L.; Ushakova-Sokolova, L.; Dovgan, N.; Potapenko, P.; Nekrasa, A.; Prokhorov, O.; Leonidova, V.; Rebrov, B.; Gamachek, O.; Rishko, M.; Chendey, T.; Rudyk, I.; Shatilo, V.; Ishchuk, V.; Shcherbak, V.; Goncharova, I.; Shvetz, N.; Zamlynskyy, M.; Sirenko, Y.; Stanislavchuk, M.; Perebetiuk, L.; Sychov, O.; Lyzohub, S.; Tseluyko, V.; Kuznetsov, I.; Tykhonova, S.; Vakaliuk, I.; Drapchak, I.; Vatutin, M.; Sklyanna, O.; Vizir, V.; Goncharov, O.; Volkov, V.; Serik, S.; Yagensky, A.; Nahrebetskyy, V.; Yena, L.; Mudruk, I.; Zharinov, O.; Logvinov, Y.; Zhurba, S.; Shandra, T.; Aggarwal, R.; Smith, S.; Beeton, I.; Dunn, S.; Blagden, M.; Price, R.; Dougal, K.; Chapman, O.; Davies, D.; Choy, A.; Duff, J.; Cohen, A.; Wilmott, R.; D'Costa, D.; Douglas, H.; Dickinson, D.; Lie, F.; Ramasamy, V.; Lindsay, S.; Atkinson, C.; Linker, N.; Finlayson, M.; Lip, G.; Brown, R.; MacCallum, P.; Ebano, P.; Macleod, M.; McGhee, C.; Marazzi, P.; Jones, D.; Maxwell, T.; Isted, C.; More, R.; Helliwell, L.; Moriarty, A.; Mackin, A.; Murdoch, D.; Andrews, A.; Newby, D.; Flint, L.; Pye, M.; Wright, L.; Avery, D.; Young, G.; Sopher, M.; Kennard, S.; Storey, R.; Bridge, C.; Turner, W.; Walker, M.; Venkataraman, A.; Gilchrist, M.; Watkin, R.; Chung, A.; Wright, A.; Wright, J.; Abi-Mansour, P.; Panella, M.; Adams, K.; Lohman, J.; Adler, J.; Barash, B.; Adler, P.; Reiling, S.; Beck, P.; Ahmad, A.; Hussain, A.; Ahmadpour, H.; Lim, G.; Akhter, F.; Brubaker, S.; Alexander, J.; Genova-Peeva, E.; Aliyar, P.; Godsey, W.; Allison, J.; Biscardi, R.; Almquist, A.; MacDonald, H.; Alsheikh, T.; Lane, B.; Amin, K.; Khetarpal, S.; Amin, M.; Persechino, F.; York, T.; Arnold, T.; Shoaf, R.; Arouni, A.; Rasmussen, L.; Attanti, S.; Strickland, S.; Aude, Y.; Cobos, D.; Awasty, V.; Baldwin, E.; Ayesu, K.; Thompson, B.; Baine, S.; Batista, M.; Baman, R.; Campbell, G.; Barber, M.; Altonen, D.; Barker, T.; Faircloth, C.; Barrington, P.; Gordon, L.; Bartkowiak, A.; Benton, J.; Beasley, R.; Hoffman, T.; Bedoya, R.; Luis-Valdes, M.; Bedwell, N.; Craig, M.; Beinart, S.; Swaim, D.; Bensimhon, D.; Garman, V.; Berk, M.; Ibarra, M.; Bernard, J.; Eldred, R.; Bilal, B.; Preston, S.; Bilazarian, S.; Langone, L.; Bingham, S.; Antonino, M.; Block, T.; Talbot-Lawson, C.; Blonder, R.; Ensminger, E.; Bloomberg, R.; Bloomberg, K.; Blue, B.; Vernon, M.; Borsheim, M.; Hickenbotham, D.; Bouchard, A.; Wade, W.; Bowden, W.; Ziegler, K.; Bradley, A.; Terry, P.; Brilakis, E.; Frey, W.; Brown, H.; Triano, A.; Bybee, K.; Al-Maliky, T.; Cader, C.; Morton, S.; Canaday, D.; Canosa, R.; Hartranft, E.; Caplan, J.; Jameson, L.; Carr, K.; Phan, D.; Chang, M.; Hatfield, G.; Charlat, M.; Tamayo, M.; Chaturvedi, S.; Sawaya, K.; Ciaramita, J.; Bagby, J.; Clapp, T.; Clay, A.; McClelland, M.; Dutka, C.; Cohen, R.; Bossaers, J.; Colan, D.; Salpas, S.; Cole, J.; Fisher, M.; Concha, M.; Martinez, E.; Corbett, B.; Svadbik, L.; Cossu, S.; Mullinax, K.; Cottiero, R.; Masson, E.; Cowan, L.; Nelson, L.; Curtis, B.; Sarpola, N.; Dang, N.; Morgan, T.; Daniels, S.; Leka, G.; Datta, S.; Wulf, A.; Dave, K.; Dave, B.; Davuluri, A.; Ebreo, N.; de Lemos, J.; Debes, C.; Dean, J.; Warmack, D.; Degarmo, R.; Carey, J.; Steward, A.; Desire, A.; Waters, L.; Devenport, S.; Briscoe, C.; Dhar, S.; Ucik, S.; DiGiovanna, M.; Tisdale, L.; Donovan, D.; Rodriguez, L.; Dotani, I.; Olson, A.; Drozdiak, R.; Habibi, S.; D'Souza, A.; Cullen, T.; Eade, J.; Dunn, K.; Eldadah, Z.; Quick, R.; Ellis, J.; Cristaldi, J.; Erenrich, N.; Johnson, C.; O'Brien, J.; Ettinger, N.; Shipp, A.; Everhart, B.; DeSalle, D.; Fahmy, R.; Watkins, D.; Feld, L.; Tameron, A.; Feldman, J.; Tang, N.; Felten, W.; Prior, J.; Fialkow, J.; Calvo, M.; Finkel, M.; Shriver, D.; Finkelstein, S.; Fischell, T.; Drew, B.; Fishbein, G.; Donahue, S.; Flores, E.; Slayton, C.; Forman, S.; Solis, A.; Frais, M.; Thrope, C.; Franco, M.; Gentry, P.; French, W.; Morales, C.; Friedlander, I.; Gaffney, M.; Jones, J.; Garb, J.; Miranda, J.; George, F.; Valentine, H.; Gerber, J.; Hinchion, N.; Gillespie, E.; Keane-Richmond, P.; Gogia, H.; Ewing, B.; Goldscher, D.; Latteri, J.; Goldstein, M.; Gowda, S.; Rafala, E.; Graham, S.; Bonora, M.; Griffin, S.; Aull, L.; Griffin, J.; Goodman, V.; Grossman, C.; Davis, A.; Grove, D.; Mabe, K.; Guarino, J.; Gabela, W.; Guarnieri, T.; Guerrero, N. N.; Foster, B.; Guthrie, R.; Felsman, D.; Gvora, T.; McLean, R.; Hack, T.; Morelli, L.; Hamroff, G.; Bentivenga, L.; Han, M.; Cavanna, L.; Harris, J.; Bobade, M.; Hearne, S.; Krater, C.; Heiman, M.; Dandekar, U.; Shah, D.; Henderson, D.; Millard, D.; Henry, S.; Harkins, V.; Hermany, P.; Batchell, K.; Herrod, J.; Miranda, D.; Herson, S.; Carey, G.; Hinchman, D.; Vieira, P.; Hippert, R.; Dutter, S.; Hoekstra, J.; Homan, J.; Homayouni, A.; Horton, K.; Sloss, D.; Hotchkiss, D.; Turner, N.; Houchin, V.; Howard, V.; Hays, D.; Howard, L.; Craft, D.; Huang, P.; Truva, C.; Hunter, J.; Battistelli, E.; Hurst, P.; Garza, M.; Hussain, M.; Tambawala, M.; Ison, R.; Butcher, S.; Jardula, M.; Andresen, T.; Johnson, F.; Phillips, T.; Jones, R.; Hughett, G.; Jovin, I.; Nichols, M.; Judson, P.; Royes, A.; Kahn, B.; Coombs, V.; Kai, W.; Dugal, J.; Kandath, D.; Kostedt, G.; Kaplan, K.; Cook, S.; Kapoor, A.; Ruggiero, M.; Karunaratne, H.; Behm, K.; Kastelic, R.; Davis, C.; Keller, R.; Keller, J.; Kerkering, M.; Bartholomaus, D.; Kersh, R.; Buhler, A.; Kesselbrenner, M.; DiCorcia, L.; Khan, B.; Binns, M.; Khan, M.; Khan, G.; Kindman, L.; Averett, P.; Korpas, D.; Godfrey, C.; Kotha, P.; Sanchez, E.; Kozlowski, J.; Watts, S.; Krichmar, P.; Marquez, D.; Laliotis, A.; Jauregui, V.; Lambert, C.; Coyle, G. Stagi; Landau, C.; Ferguson, D.; Lang, J.; Simmons, T.; Langevin, E.; Faucett, S.; Ledbetter, L.; Royse, H.; Lentz, M.; Smith, D.; Lesser, M.; Hartley, L.; Lewis, D.; Bonds, C.; Lillestol, M.; Miller, D.; Ling, L.; Murphy, R.; Littlefield, R.; Wofford, E.; Lomnitz, D.; Lone, B.; Davids, M.; Looby, R.; Ault, S.; Lui, H.; Wright, H.; Lurie, M.; Edelstein, J.; Macomber, J.; Bush, D.; Magee, A.; Doctor, A.; Mainigi, S.; Lisiecki, B.; Makam, S.; Casas, R.; Mandviwala, M.; Marar, I.; Rabadi-Marar, D.; Marenberg, M.; Bedenko, E.; Massin, E.; Hicks, T.; McCartney, M.; Stubbs, L.; McGarvey, J.; Schwarz, L.; McGuire, K.; McKenzie, M.; Rodkey, K.; McKnight, T.; Paul, J.; McLaurin, B.; Lack, A.; Mega, J.; Marti, J.; Meholick, A.; Skinner, J.; Mehrle, A.; Wall, J.; Mendelson, R.; Cervellione, K.; Mercado, A.; Cajulis, C.; Michlin, B.; Romero-Colon, J.; Milas, J.; Sanders, D.; Miller, R.; Sanchez, S.; Miller, S.; Gryczan, J.; Mody, F.; Strugatsky, S.; Moran, J.; Garner, S.; Morledge, J.; Bowman, B.; Mouhaffel, A.; Parrott, N.; Mounsey, P.; Schuler, C.; Mowdy, M.; Todd, S.; Mullen, P.; Raziano, S.; Murphy, A.; Oehmann, V.; Nadar, V.; Parker, A.; Naidu, J.; West, M.; Nallasivan, M.; Goza, J.; Nguyen, T.; Nomanee, S.; Nielsen, R.; Wilmot, M.; Oberoi, M.; Thakkar, N.; Oppenheimer, K.; McCormick, J.; Orchard, R.; Garcia, L.; Osborne, J.; Gonzalez, M.; Oza, S.; Joseph, L.; Patnam, S.; Dennison, K.; Pavon, H.; Gorry, N.; Pearlstein, R.; Montayne, S.; Pentz, W.; Duncan, D.; Peters, P.; Chacon, L.; Petruzziello, F.; Morlando, F.; Pettis, K.; Brown, F.; Pezzella, S.; Kirk, D.; Poulathas, A.; Cush, S.; Pratt, R.; Neeper, L.; Pribble, A.; Lowe, K.; Pudi, K.; Sham, L.; Pugeda, J.; Ebert, J.; Quadrel, M.; Rafla, E.; Quinlan, E.; Reed, C.; Quinn, J.; Hemmen, C.; Rama, P.; Domingo, D.; Redondo, V.; Wroblewski, J.; Renzi, M.; Stanley, E.; Richwine, R.; Pazier, P.; Riofrio, K.; Braun, D.; Robinson, J.; Cherrico, M.; Roehll, W.; Hollihan, P.; Rosado, N. N.; Barnhorst, M.; Rosado, J.; Bamhorst, M.; Rosen, R.; Martin, C.; Ross, S.; Freeman, R.; Ruoff, G.; Nelson, T.; Sacco, J.; Ball, E.; Samal, A.; Schomburg, J.; Sandberg, J.; Lafave, J.; Savin, V.; Clifton, R.; Schaefer, S.; Fekete, A.; Schneider, R.; Schneider, W.; Schulman, D.; Mercer, S.; Seals, A.; Ullig, T.; Holt, A.; Seide, H.; Mather, N.; Shah, G.; Witt, P.; Shalaby, A.; Seese, M.; Shanes, J.; Fleets, J.; Shaoulian, E.; Hren, A.; Sheikh, K.; Hengerer, T.; Shih, H.; Browning, J.; Shoukfeh, M.; Stephenson, L.; Siler, T.; Champagne, M.; Simpson, P.; Meyer, R.; Singh, N.; Turner, K.; Singh, V.; Nelson, M.; Skierka, R.; Hughes, B.; Keene, R.; Smith, R.; Hodnett, P.; Spangenthal, S.; Thomason, L.; Sperling, M.; Vasquez, E.; Spivack, E.; McCartney, P.; Staniloae, C.; Liu, M.; Steljes, A.; Cox, C.; Struble, R.; Vittitow, T.; Suresh, D.; Frost, J.; Swerchowsky, V.; Freemyer, D.; Szulawski, I.; Herwehe, S.; Tahirkheli, N.; Springer, K.; Takata, T.; Bruton, T.; Talano, J.; Leo, L.; Tami, L.; Corchado, D.; Tatarko, M.; Swauger, M.; Tawney, K.; Dastoli, K.; Teague, S.; Young, K.; tee, H.; Mitchell, T.; Teixeira, J.; Southam, D.; Torres, M.; Tucker, P.; Salas, L.; Updegrove, J.; Hanna, K.; Val-Mejias, J.; Harrelson, K. Gonzalez; Vemireddy, D.; Cardoza, T.; Verma, S.; Parsons, T.; Vicari, R.; Warren, K.; Vijay, N.; Washam, M.; Vossler, M.; Kilcup, S.; Walsh, R.; Renaud, K.; Ward, S.; Locklear, T.; Waxman, F.; Sanchez, G.; Weiss, R.; St Laurent, B.; Westcott, J.; Williams, D.; Gibson, C.; Williams, R.; Dowling, C.; Willis, J.; VonGerichten, S.; Wood, K.; Capasso-Gulve, E.; Worley, S.; Pointer, S.; Yarows, S.; Sheehan, T.; Yasin, M.; Yi, J.; Dongas, B.; Yousuf, K.; Zakhary, B.; Curtis, S.; Zeig, S.; Mason, T.; Zellner, C.; Harden, M.; Roper, E.; Waseem, M.; Grammer, M.

    2013-01-01

    BackgroundEdoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. MethodsWe conducted a randomized, double-blind, double-dummy trial comparing two

  18. Evaluation of Patients' Knowledge on Warfarin Therapy Among ...

    African Journals Online (AJOL)

    It was based on cross sectional study design in which 130 patients receiving warfarin were interviewed using oral anticoagulation knowledge (OAK) questionnaires composed of 20 multiple choice questions. Ethical approval was obtained from the School of Pharmacy Ethics Review Board before the data collection process ...

  19. Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).

    Science.gov (United States)

    Halperin, Jonathan L; Hankey, Graeme J; Wojdyla, Daniel M; Piccini, Jonathan P; Lokhnygina, Yuliya; Patel, Manesh R; Breithardt, Günter; Singer, Daniel E; Becker, Richard C; Hacke, Werner; Paolini, John F; Nessel, Christopher C; Mahaffey, Kenneth W; Califf, Robert M; Fox, Keith A A

    2014-07-08

    Nonvalvular atrial fibrillation is common in elderly patients, who face an elevated risk of stroke but difficulty sustaining warfarin treatment. The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). This prespecified secondary analysis compares outcomes in older and younger patients. There were 6229 patients (44%) aged ≥75 years with atrial fibrillation and ≥2 stroke risk factors randomized to warfarin (target international normalized ratio=2.0-3.0) or rivaroxaban (20 mg daily; 15 mg if creatinine clearance <50 mL/min), double blind. The primary end point was stroke and systemic embolism by intention to treat. Over 10 866 patient-years, older participants had more primary events (2.57% versus 2.05%/100 patient-years; P=0.0068) and major bleeding (4.63% versus 2.74%/100 patient-years; P<0.0001). Stroke/systemic embolism rates were consistent among older (2.29% rivaroxaban versus 2.85% warfarin per 100 patient-years; hazard ratio=0.80; 95% confidence interval, 0.63-1.02) and younger patients (2.00% versus 2.10%/100 patient-years; hazard ratio=0.95; 95% confidence interval, 0.76-1.19; interaction P=0.313), as were major bleeding rates (≥75 years: 4.86% rivaroxaban versus 4.40% warfarin per 100 patient-years; hazard ratio=1.11; 95% confidence interval, 0.92-1.34; <75 years: 2.69% versus 2.79%/100 patient-years; hazard ratio=0.96; 95% confidence interval, 0.78-1.19; interaction P=0.336). Hemorrhagic stroke rates were similar in both age groups; there was no interaction between age and rivaroxaban response. Elderly patients had higher stroke and major bleeding rates than younger patients, but the efficacy and safety of rivaroxaban relative to warfarin did not differ with age, supporting rivaroxaban as an alternative for the elderly. © 2014 American Heart Association, Inc.

  20. Safety of warfarin therapy during cataract surgery under topical anesthesia

    Directory of Open Access Journals (Sweden)

    Newton Kara-Junior

    2015-06-01

    Full Text Available ABSTRACT Purpose: To analyze the safety of warfarin therapy during cataract surgery under topical anesthesia. Methods: This was a prospective nonrandomized comparative study of 60 eyes of 60 patients treated with or without concurrent oral warfarin anticoagulant therapy, referred for cataract surgery under topical anesthesia. The sample included a treatment (n=30 and a control (n=30 group. Results: There were no records of intraoperative or postoperative intracameral bleeding complications in both the groups. At 1-month postoperative follow-up, 90.0% of patients presented spectacle-corrected visual acuity of at least 20/40. Conclusion: Cataract surgery by phacoemulsification with topical anesthesia can be successfully conducted without discontinuing warfarin.

  1. Warfarin interaction with Matricaria chamomilla.

    Science.gov (United States)

    Segal, Robert; Pilote, Louise

    2006-04-25

    No cases have been reported of Matricaria chamomilla potentiating the effects of warfarin. Nevertheless there is a theoretical risk for potentiation, since the herb is thought to be a coumarin constituent. We describe the case of a 70-year-old woman who, while being treated with warfarin, was admitted to hospital with multiple internal hemorrhages after having used chamomile products (tea and body lotion) to soothe upper respiratory tract symptoms. Patient education on the potential risk of taking chamomile products while being treated with warfarin is necessary to avoid such occurrences.

  2. Genetics Home Reference: warfarin sensitivity

    Science.gov (United States)

    ... warfarin sensitivity , the most common sign is excessive internal bleeding, which is often seen when individuals with ... of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, Bethesda, MD 20894, USA HONCode ...

  3. Warfarin interaction with Matricaria chamomilla

    OpenAIRE

    Segal, Robert; Pilote, Louise

    2006-01-01

    No cases have been reported of Matricaria chamomilla potentiating the effects of warfarin. Nevertheless there is a theoretical risk for potentiation, since the herb is thought to be a coumarin constituent. We describe the case of a 70-year-old woman who, while being treated with warfarin, was admitted to hospital with multiple internal hemorrhages after having used chamomile products (tea and body lotion) to soothe upper respiratory tract symptoms. Patient education on the potential risk of t...

  4. Acute Abdomen Due to Uncontrolled Use of Warfarin: Spontaneous Intra-abdominal

    Directory of Open Access Journals (Sweden)

    Fatih Dal

    2017-12-01

    Full Text Available Warfarin is an oral anticoagulant, which is commonly used in the treatment and prophylaxis of thromboembolic conditions. Bleeding is the primary adverse effect associated with warfarin. The majority of warfarin-related bleedings are spontaneous minor hemorrhages occurring in the subcutaneous or intramuscular tissues and can be treated by decreasing the dose of oral anticoagulants. However, although rare, it is possible to encounter spontaneous major bleedings with increased risk of mortality. Conservative approach is the preferred initial therapy for hemodynamically stable patients with major intra-abdominal hemorrhages that we define as the intermediate group patients. Nevertheless, surgery is required for hemodynamically unstable patients with acute abdominal pain in cases of ongoing active hemorrhage, generalized peritonitis, obstruction, acute abdomen, intestinal ischemia, and perforation. In this article, we present a rare case of acute abdomen and spontaneous intra-abdominal hemorrhage resulting from uncontrolled use of warfarin and a new classification requirement.

  5. Comparison of the phase III clinical trial designs of novel oral anticoagulants versus warfarin for the treatment of nonvalvular atrial fibrillation: implications for clinical practice.

    Science.gov (United States)

    Gonzalez-Quesada, Carlos J; Giugliano, Robert P

    2014-04-01

    Although vitamin K antagonists (VKAs) have been the backbone of thromboprophylaxis in nonvalvular atrial fibrillation, their limitations have encouraged the development of a new generation of oral anticoagulants. This review compares the different designs and procedures used to conduct four phase III trials that tested dabigatran, rivaroxaban, apixaban, and edoxaban versus VKAs. Although pharmacologic characteristics and results of the main trials are briefly discussed, this review mainly focuses on study designs, enrollment criteria, populations studied, quality metrics, and transition strategies between oral anticoagulants. While each of the trials was of high quality, performed independently, and led by independent academic groups, substantial differences exist in terms of drug pharmacology and trial characteristics. Caution is advised when comparing results across trials as practicing clinicians strive to personalize anticoagulation treatments for their individual patients. We believe that the differences in the pharmacokinetic and pharmacodynamic profiles of the available novel oral anticoagulants (NOACs), coupled with substantial heterogeneity in the trial populations and designs and procedures used to conduct the trials, support an important role for each of the NOACs dependent upon the specific clinical scenario faced by the practicing clinician.

  6. Clinical Prediction Model for Time in Therapeutic Range While on Warfarin in Newly Diagnosed Atrial Fibrillation.

    Science.gov (United States)

    Williams, Brent A; Evans, Michael A; Honushefsky, Ashley M; Berger, Peter B

    2017-10-12

    Though warfarin has historically been the primary oral anticoagulant for stroke prevention in newly diagnosed atrial fibrillation (AF), several new direct oral anticoagulants may be preferred when anticoagulation control with warfarin is expected to be poor. This study developed a prediction model for time in therapeutic range (TTR) among newly diagnosed AF patients on newly initiated warfarin as a tool to assist decision making between warfarin and direct oral anticoagulants. This electronic medical record-based, retrospective study included newly diagnosed, nonvalvular AF patients with no recent warfarin exposure receiving primary care services through a large healthcare system in rural Pennsylvania. TTR was estimated as the percentage of time international normalized ratio measurements were between 2.0 and 3.0 during the first year following warfarin initiation. Candidate predictors of TTR were chosen from data elements collected during usual clinical care. A TTR prediction model was developed and temporally validated and its predictive performance was compared with the SAMe-TT 2 R 2 score (sex, age, medical history, treatment, tobacco, race) using R 2 and c-statistics. A total of 7877 newly diagnosed AF patients met study inclusion criteria. Median (interquartile range) TTR within the first year of starting warfarin was 51% (32, 67). Of 85 candidate predictors evaluated, 15 were included in the final validated model with an R 2 of 15.4%. The proposed model showed better predictive performance than the SAMe-TT 2 R 2 score ( R 2 =3.0%). The proposed prediction model may assist decision making on the proper mode of oral anticoagulant among newly diagnosed AF patients. However, predicting TTR on warfarin remains challenging. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  7. Ischaemic and haemorrhagic stroke associated with non-vitamin K antagonist oral anticoagulants and warfarin use in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Staerk, Laila; Fosbøl, Emil Loldrup; Lip, Gregory Y. H.

    2017-01-01

    BACKGROUND: Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) are widely used as stroke prophylaxis in non-valvular atrial fibrillation (AF), but comparative data are sparse. PURPOSE: To compare dabigatran, rivaroxaban, and apixaban vs. VKA and the risk of stroke/thromboembolism (TE......) and intracranial bleeding in AF. METHODS: Using Danish nationwide registries (2011-15), anticoagulant-naïve AF patients were identified when initiating VKA or an NOAC. Outcomes were stroke/TE and intracranial bleeding. Multiple outcome-specific Cox regression was performed to calculate average treatment effects...... as standardized differences in 1-year absolute risks. RESULTS: Overall, 43 299 AF patients initiated VKA (42%), dabigatran (29%), rivaroxaban (13%), and apixaban (16%). Mean CHA2DS2-VASc (SD) score was: VKA 2.9 (1.6), dabigatran 2.7 (1.6), rivaroxaban 3.0 (1.6), and apixaban 3.1 (1.6). Within patient...

  8. [Patient with warfarin poisoning caused by coumarin rodenticide].

    Science.gov (United States)

    Matsuda, Kimiko; Okamoto, Misao; Higaki, Atsushi; Konno, Yousuke; Tohyama, Kaoru; Ichihara, Kiyoshi; Suzuki, Kouitiro

    2008-04-01

    We report a patient who attempted suicide by taking warfarin as a coumarin rodenticide twice, and showed oral bleeding and an abnormally prolonged bleeding tendency after 10 days. He was conscious. His body temperature was 36.6 degrees C, the respiratory rate was 23/min, and blood pressure was 142/87 mmHg. A bite wound showing continuous bleeding was observed on the right side of the oral cavity. CT of the head and upper gastrointestinal endoscopy showed no intracranial and gastrointestinal bleeding,respectively. The PT and INR were extremely high, and complete blood count revealed anemia. Blood chemistry showed hypoproteinemia. Occult blood was strongly positive. Routine urine examination and electrocardiography showed neither abnormal nor characteristic findings. In drug/ poison screening tests, GC/MS analysis revealed warfarin artifacts in serum and urine samples. Warfarin was isolated from each sample, converted to a TMS derivative, and quantified by SIM analysis of GC/MS. During the clinical course, KaytwoN (vitamin K) was intravenously administered at a dose of 20 mg since the INR at the first consultation was 20.89. After admission to the ICU, 20 mg Kaywan (vitamin K) was orally administered, and the INR after 5 hours improved to 2.32. Kaywan administration (20 mg/day) was initiated, and he improved and was discharged 5 days after admission. The definite cause could be clarified by drug/poison analysis, and effective treatment could be performed.

  9. Pionerer bag vitamin K, dikumarol og warfarin

    DEFF Research Database (Denmark)

    Norn, Svend; Permin, Henrik; Kruse, Edith

    2014-01-01

    The history of the discovery and development of vitamin K and its antagonists, the oral anticoagulants dicoumarol and warfarin, are fascinating, triumphant landmarks in the annals of medicine. Vitamin K was found by Carl Peter Henrik Dam and Fritz Schønheyder from the University of Copenhagen....... The discovery was initiated by Dam, by a lucky choice of chicks in the dissertation of sterol metabolism, since the vitamin is not formed by intestinal bacteria in these animals. In these experiments the lack of an unknown factor in the synthetic diet caused internal bleeding similar to that found in scurvy......, but the bleeding was not reversed by vitamin C and it could not be explained by the lack of classical vitamins. In 1935 the unknown antihaemorrhagic factor was named vitamin K and a few months later the phenomenon was also observed by H.J. Almquist and E.L.R. Stokstad in Berkeley. The activity of the factor...

  10. Probable warfarin and dapsone interaction.

    Science.gov (United States)

    Truong, Teresa; Haley, James

    2012-01-01

    We describe a case of a 41-year-old woman who was stable for over a year on 22.5 mg/week of warfarin. At a follow-up visit, her international normalized ratio (INR) was found to be supratherapeutic at 3.9. Her only significant change was acyclovir initiation for shingles, and clindamycin and dapsone for infection on her right foot. An interaction report was run using Micromedex with no interactions reported. Sixteen percent of the weekly dose was held and maintenance dose was continued. Two weeks later, the INR remained supratherapeutic at 4.3, with discontinuation of clindamycin and dapsone, 5 days earlier, as the only change. This time an interaction report was run using Lexi-Comp, which identified an interaction between warfarin and dapsone. The INR has been therapeutic and stable since discontinuation of transient factors. It is hypothesized that warfarin and dapsone compete for binding on the CYP2C9 and CYP3A4 isoenzymes and therefore serum concentration of warfarin was elevated.

  11. Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).

    Science.gov (United States)

    Sherwood, Matthew W; Douketis, James D; Patel, Manesh R; Piccini, Jonathan P; Hellkamp, Anne S; Lokhnygina, Yuliya; Spyropoulos, Alex C; Hankey, Graeme J; Singer, Daniel E; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Becker, Richard C

    2014-05-06

    During long-term anticoagulation in atrial fibrillation, temporary interruptions (TIs) of therapy are common, but the relationship between patient outcomes and TIs has not been well studied. We sought to determine reasons for TI, the characteristics of patients undergoing TI, and the relationship between anticoagulant and outcomes among patients with TI. In the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF), a randomized, double-blind, double-dummy study of rivaroxaban and warfarin in nonvalvular atrial fibrillation, baseline characteristics, management, and outcomes, including stroke, non-central nervous system systemic embolism, death, myocardial infarction, and bleeding, were reported in participants who experienced TI (3-30 days) for any reason. The at-risk period for outcomes associated with TI was from TI start to 30 days after resumption of study drug. In 14 236 participants who received at least 1 dose of study drug, 4692 (33%) experienced TI. Participants with TI were similar to the overall ROCKET AF population in regard to baseline clinical characteristics. Only 6% (n=483) of TI incidences involved bridging therapy. Stroke/systemic embolism rates during the at-risk period were similar in rivaroxaban-treated and warfarin-treated participants (0.30% versus 0.41% per 30 days; hazard ratio [confidence interval]=0.74 [0.36-1.50]; P=0.40). Risk of major bleeding during the at-risk period was also similar in rivaroxaban-treated and warfarin-treated participants (0.99% versus 0.79% per 30 days; hazard ratio [confidence interval]=1.26 [0.80-2.00]; P=0.32). TI of oral anticoagulation is common and is associated with substantial stroke risks and bleeding risks that were similar among patients treated with rivaroxaban or warfarin. Further investigation is needed to determine the optimal management strategy in patients with atrial fibrillation

  12. The effect of height and weight adjusted dose of intrathecal hyperbaric bupivacaine for elective caesarean section

    Directory of Open Access Journals (Sweden)

    A Subedi

    2011-03-01

    Full Text Available Introduction: The study compared spinal anesthesia using intrathecal hyperbaric bupivacaine between height and weight adjusted dose and fi xed dose during caesarean section. Methods: A hundred parturients, who had given their consent and were scheduled for elective caesarean section under spinal anesthesia, were randomly assigned into two groups. We adjusted the intrathecal dose of heavy bupivacaine (0.5 % according to the height and weight of patients (Group AD from Harten’s dose chart developed from the Caucasian parturients and the fi xed dose (2.2 ml was used in Group FD patients. Keeping the observer blinded to the study groups, the onset time to sensory block up to T5, haemodynamic changes, side effects, and fetal outcome were observed. Results: The median onset time of spinal block in Group FD was faster than in Group AD (6 min vs. 4 min; p = 0.01. The spinal block level extended above T3 level in a signifi cantly (p < 0.05 larger number of patients 12 (24 % in Group FD than in one (2 % patient in Group AD. A signifi cantly (p < 0.05 larger number of patients, 32, (64 % in Group FD had hypotension than in 15 (30 % patients in Group AD. The lowest recorded SAP (101 ± 6 mm Hg in Group AD was higher than in Group FD (96 ± 6.7 mm Hg. Nausea and vomiting were more pronounced in Group FD patients. Conclusions: The bupivacaine dose was signifi cantly reduced on its dose adjustment for the body weight and height of patients for cesearean section. This adjusted-dose use suitably restricted spinal block level for cesarean section with a distinct advantage of less hypotension and with a similar neonatal outcome as fi xed compared with the dose use. keywords: caesarean section; low-dose hyperbaric bupivacaine; spinal anesthesia.

  13. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy

    OpenAIRE

    Kaya, Bülent; Yildiz, Ibrahim; Baha, Reshat Mehmet; Zeytun, Neslihan Ebru Eryaşar; Yetisgen, Azize

    2015-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin.

  14. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy.

    Science.gov (United States)

    Kaya, Bülent; Yildiz, Ibrahim; Baha, Reshat Mehmet; Zeytun, Neslihan Ebru Eryaşar; Yetisgen, Azize

    2015-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin.

  15. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy

    Directory of Open Access Journals (Sweden)

    Bülent Kaya

    2015-01-01

    Full Text Available Diffuse alveolar hemorrhage (DAH is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin.

  16. WARFARIN IN PATIENTS WITH CARDIOEMBOLIC STROKE

    Directory of Open Access Journals (Sweden)

    E. N. Dankovtseva

    2012-01-01

    Full Text Available Analysis of the current literature data on the use of warfarin in patients with cardioembolic stroke is presented. Cardioembolic stroke pathology and particularities of this condition therapywith antithrombotic medications are shown in details. Possibility to apply thrombolysis during warfarin treatment and the use of anticoagulants after cardioembolic stroke is discussed.

  17. Profile and anticoagulation outcomes of patients on warfarin therapy in an urban hospital in Cape Town, South Africa

    Directory of Open Access Journals (Sweden)

    Babatunde O. Sonuga

    2016-03-01

    Full Text Available Background: Warfarin is the most frequently used oral anticoagulant worldwide and it is the oral anticoagulant of choice in South Africa for reducing thrombosis-related morbidity and mortality. However, the safety and efficacy of warfarin therapy depends mainly on careful monitoring and maintenance of the international normalised ratio (INR within an optimal therapeutic range.Aim: The aim of this study was to describe the profile and the anticoagulation outcomes of patients on warfarin therapy in a major warfarin clinic in the Western Cape Province of South Africa. Setting: Victoria Hospital - a district hospital in Cape Town. Methods: A cross sectional review of clinical records of patients on warfarin therapy who attended the INR clinic from 01 January 2014 to 30 June 2014 was done. Data analysis was done with STATA to generate appropriate descriptive data.Results: Our study showed that atrial fibrillation (AF was the commonest indication for warfarin use in this study and hypertension was the commonest comorbidity among these patients. Only 48.5% achieved target therapeutic range; 51.5% were out-of-range. There was a significant association between alcohol consumption and poor anticoagulation outcomes (p-value < 0.022. Anticoagulation outcomes were better among the older age groups, male patients and in those with AF. The prevalence of thrombotic events while on warfarin treatment was 2.2%, while prevalence of haemorrhagic events was 14%. Most of the patients with bleeding events were on concurrent use of warfarin and other medications with potential drug interactions.Conclusion: In our study, patients who achieved target therapeutic control were less than the acceptable 60%.Keywords: Oral anticoagulant, anticoagulation outcomes, therapeutic control, percentage INR within target therapeutic range (%ITTR,Time in therapeutic range (TIR

  18. Intramural duodenal hematoma as a complication of therapy with Warfarin: a case report and literature review

    International Nuclear Information System (INIS)

    Faria, Juliano; Pessoa, Roberta; Hudson, Marcelo; Vitoi, Silvio; Villela, Ovidio; Torres, Jose; Paula, Mara Delgado; Bemvindo, Aloisio

    2004-01-01

    We report a case of a patient receiving chronic oral anticoagulant therapy with Warfarin who presented with acute intestinal obstruction. Computed tomography showed intramural duodenal hematoma. Treatment was conservative with correction of the coagulation parameters and observation. This case exemplifies the usefulness of conservative therapy and computed tomography in patients with acute small bowel obstruction receiving anticoagulant therapy. (author)

  19. Abnormal vaginal bleeding in women with venous thromboembolism treated with apixaban or warfarin

    NARCIS (Netherlands)

    Brekelmans, Marjolein P. A.; Scheres, Luuk J. J.; Bleker, Suzanne M.; Hutten, Barbara A.; Timmermans, Anne; Büller, Harry R.; Middeldorp, Saskia

    2017-01-01

    Abnormal vaginal bleeding can complicate direct oral anticoagulant (DOAC) treatment. We aimed to investigate the characteristics of abnormal vaginal bleeding in patients with venous thromboembolism (VTE) receiving apixaban or enoxaparin/warfarin. Data were derived from the AMPLIFY trial. We compared

  20. Warfarin-induced Primary Dissection of Lower Peripheral Arteries: A Case Report

    International Nuclear Information System (INIS)

    Lee, Jae A; You, He Chul; Han, Young Min; Kwak, Hyo Sung

    2010-01-01

    Primary dissection of a peripheral artery without involvement of the aorta is a rare entity. Warfarin is currently used as the standard oral anticoagulant in a variety of clinical settings. We report here on a case of focal dissection of the common iliac artery and the superficial femoral artery following prophylactic treatment with warfarin for a prosthetic heart valve. The patient's laboratory results showed a high international normalized ratio and prolongation of the activated partial thromboplastin time. Angiography showed a dissection of the left common iliac artery and the right superficial femoral artery. His symptoms immediately disappeared after deploying stents to the arterial dissections

  1. Cardioversion and Risk of Adverse Events with Dabigatran versus Warfarin-A Nationwide Cohort Study.

    Directory of Open Access Journals (Sweden)

    Jannik Langtved Pallisgaard

    Full Text Available Cardioversion can rapidly and effectively restore sinus rhythm in patients with persistent atrial fibrillation. Since 2011 dabigatran has been available as an alternative to warfarin to prevent thromboembolic events in patients with non-valvular atrial fibrillation undergoing cardioversion. We studied time to cardioversion, risk of adverse events, and risk of readmission with atrial fibrillation after cardioversion according to anticoagulation therapy.Through the nationwide Danish registries we included 1,230 oral anticoagulation naïve patients with first time non-valvular atrial fibrillation and first time cardioversion from 2011 to 2012; 37% in the dabigatran group (n = 456, and 63% in the warfarin group (n = 774. Median time to cardioversion was 4.0 (interquartile range [IQR] 2.9 to 6.5 and 6.9 (IQR 3.9 to 12.1 weeks in the dabigatran and warfarin groups respectively, and the adjusted odds ratio of cardioversion within the first 4 weeks was 2.3 (95% confidence interval [CI] 1.7 to 3.1 in favor of dabigatran. The cumulative incidence of composite endpoint of stroke, bleeding or death were 2.0% and 1.0% at 30 weeks in the warfarin and dabigatran groups respectively, with an adjusted hazard ratio of 1.33 (95% CI 0.33 to 5.42. Cumulative incidence of readmission with atrial fibrillation after 30 weeks were 9% and 11% in the warfarin and dabigatran groups, respectively, and an adjusted hazard ratio of 0.66 (95% CI 0.41 to 1.08.Anticoagulation treatment with dabigatran allows shorter time to cardioversion for atrial fibrillation than warfarin, and appears to be an effective and safe alternative treatment strategy to warfarin.

  2. Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient

    Directory of Open Access Journals (Sweden)

    Dagmar F. Hernandez-Suarez MD

    2016-12-01

    Full Text Available Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results—including coagulation parameters—were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient’s warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient’s international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1*2 (g.559C>T, p.P187S polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care.

  3. Potential of a Pharmacogenetic-Guided Algorithm to Predict Optimal Warfarin Dosing in a High-Risk Hispanic Patient

    Directory of Open Access Journals (Sweden)

    Dagmar F. Hernandez-Suarez MD

    2016-12-01

    Full Text Available Deep abdominal vein thrombosis is extremely rare among thrombotic events secondary to the use of contraceptives. A case to illustrate the clinical utility of ethno-specific pharmacogenetic testing in warfarin management of a Hispanic patient is reported. A 37-year-old Hispanic Puerto Rican, non-gravid female with past medical history of abnormal uterine bleeding on hormonal contraceptive therapy was evaluated for abdominal pain. Physical exam was remarkable for unspecific diffuse abdominal tenderness, and general initial laboratory results—including coagulation parameters—were unremarkable. A contrast-enhanced computed tomography showed a massive thrombosis of the main portal, splenic, and superior mesenteric veins. On admission the patient was started on oral anticoagulation therapy with warfarin at 5 mg/day and low-molecular-weight heparin. The prediction of an effective warfarin dose of 7.5 mg/day, estimated by using a recently developed pharmacogenetic-guided algorithm for Caribbean Hispanics, coincided with the actual patient’s warfarin dose to reach the international normalized ratio target. We speculate that the slow rise in patient’s international normalized ratio observed on the initiation of warfarin therapy, the resulting high risk for thromboembolic events, and the required warfarin dose of 7.5 mg/day are attributable in some part to the presence of the NQO1 *2 (g.559C>T, p.P187S polymorphism, which seems to be significantly associated with resistance to warfarin in Hispanics. By adding genotyping results of this novel variant, the predictive model can inform clinicians better about the optimal warfarin dose in Caribbean Hispanics. The results highlight the potential for pharmacogenetic testing of warfarin to improve patient care.

  4. Medication Error When Switching from Warfarin to Rivaroxaban Leading to Spontaneous Large Ecchymosis of the Abdominal and Chest Wall.

    Science.gov (United States)

    Egger, Flavio; Targa, Federica; Unterholzner, Ivan; Grant, Russell P; Herrmann, Markus; Wiedermann, Christian J

    2016-08-08

    Non-vitamin K oral anticoagulant (NOAC) therapy may be inappropriate if prescription was incorrect, the patient's physiological parameters change, or interacting concomitant medications are erroneously added. The aim of this report was to illustrate inappropriate NOAC prescription in a 78-year-old woman with non-valvular atrial fibrillation and borderline renal dysfunction who was switched from warfarin to rivaroxaban and subsequently developed bruising with hemorrhagic shock and acute on chronic renal failure. Administration of 4-factor prothrombin complex concentrate effectively reversed coagulopathy and stopped bleeding. Retrospective determination of circulating plasma levels of rivaroxaban and warfarin confirmed that excessive anticoagulation was likely due to warfarin that the patient probably continued to take although rivaroxaban was initiated. Pharmacodynamic interaction between rivaroxaban and warfarin may not only be additive but synergistic. In patients at high risk of complications, judicious prescribing and dosing of NOACs, and regular monitoring of concomitant medications and renal function are highly recommended.

  5. Warfarin therapeutic monitoring: is 70% time in the therapeutic range the best we can do?

    Science.gov (United States)

    Lader, E; Martin, N; Cohen, G; Meyer, M; Reiter, P; Dimova, A; Parikh, D

    2012-08-01

    Warfarin, an oral anticoagulant, which has been in clinical use for over sixty years, remains a challenge for clinicians to utilize, given the multiplicity of items which can limit its efficacy. Our objective is to review the evidence and comment on whether INR control can be better than has been currently reported in various studies. The duration of time a patient's international normalized ratio (INR) is maintained within the therapeutic range (time in the therapeutic range, TTR) for his or her particular indication for the drug impacts the effectiveness and safety of warfarin therapy. Maintaining a therapeutic INR while on warfarin is difficult, and numerous studies employing various strategies confirm the challenge, but not the impossibility of achieving a TTR above 70%. Maintaining a therapeutic INR requires a dedicated multi-faceted approach. With diligence, skill and various therapeutic strategies, a TTR >70% can be achieved. © 2011 Blackwell Publishing Ltd.

  6. Comparison of benefit between dabigatran and warfarin among patients with atrial fibrillation: A systematic review

    Directory of Open Access Journals (Sweden)

    Amal K Sulieman

    2016-01-01

    Full Text Available Warfarin is recognized as the standard antithrombotic agent for stroke prevention. However, new oral anticoagulant such as dabigatran constitutes huge improvement to compensate for the limitation of warfarin. A literature review was performed to compare and contrast the overall benefit of dabigatran and warfarin among patients with atrial fibrillation. We utilized HighWire as the data source for randomized controlled trials based on inclusion and exclusion criteria (from January 2007 to September 2013. Descriptive and quantitative information related to stroke and major bleeding were extracted from each trial. After a comprehensive screening of 298 search results, 17 studies which enrolled a total of 127,594 patients were included. Warfarin was found to have higher mean event rates for incidence of stroke, major bleeding, and net clinical benefit compared to dabigatran 110 mg and dabigatran 150 mg. Dabigatran 110 mg has higher rate of stroke and net clinical benefit than dabigatran 150 mg with less major hemorrhage. Overall, dabigatran had higher efficacy and safety profile than warfarin. Further research is required to determine the clinical feasibility of dabigatran in real-life practice.

  7. The effects of ferulic acid on the pharmacokinetics of warfarin in rats after biliary drainage

    Directory of Open Access Journals (Sweden)

    Li H

    2016-07-01

    Full Text Available Haigang Li,1,2 Yang Wang,1 Rong Fan,1 Huiying Lv,3 Hua Sun,4 Haitang Xie,4 Tao Tang,1 Jiekun Luo,1 Zian Xia1 1Department of Integrated Traditional Chinese and Western Medicine, Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, 2Department of Pharmacy, Changsha Medical University, 3Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, 4Anhui Provincial Centre for Drug Clinical Evaluation, Yijishan Hospital of Wannan Medical College, Wuhu, People’s Republic of China Abstract: According to previous research studies, warfarin can be detected in human bile after oral administration. Ferulic acid (FA is the main bioactive component of many Chinese herbs for the treatment of cardiovascular disease. To elucidate the effects of FA on the pharmacokinetics of warfarin in rats after biliary drainage is necessary. Twenty rats were randomly divided into four groups: Group 1 (WN: healthy rats after the administration of warfarin sodium, Group 2 (WO: a rat model of biliary drainage after the administration of warfarin sodium, Group 3 (WFN: healthy rats after the administration of warfarin sodium and FA, and Group 4 (WFO: a rat model of biliary drainage after the administration of warfarin sodium and FA. Blood samples were collected at different time points after administration. The concentrations of blood samples were determined by ultraperformance liquid chromatography–tandem mass spectrometry. Comparisons between groups were performed according to the main pharmacokinetic parameters calculated by the DAS 2.1.1 software. The pharmacokinetic parameters showed a significant difference between the WN and WO groups, the WO group showed a decrease of 51% and 41.6% in area under the curve from 0 to time (AUC0–t and peak plasma concentration (Cmax, respectively, whereas time to Cmax (Tmax was delayed 3.27 folds. There were significant differences between the WFO and WFN groups, the WFO

  8. Inappropriate combination of warfarin and aspirin.

    Science.gov (United States)

    Turan, Burak; Demir, Hakan; Mutlu, Ayhan; Daşlı, Tolga; Erkol, Ayhan; Erden, İsmail

    2016-03-01

    A combination of warfarin and aspirin is associated with increased bleeding compared with warfarin monotherapy. The aim of the study was to investigate the incidence and appropriateness of the combination of warfarin and aspirin in patients with atrial fibrillation (AF) or mechanical heart valve (MHV). This cross-sectional study included consecutive patients with AF or MHV on chronic warfarin therapy (>3 months) without acute coronary syndrome or have not undergone a revascularization procedure in the preceding year. Medical history, concomitant diseases, and treatment data were acquired through patient interviews and from hospital records. Three hundred and sixty patients (213 with AF, 147 with MHV) were included. In those with AF, a significantly higher warfarin-aspirin combination was observed with concomitant vascular disease (38.8% vs. 14.6%), diabetes (36.6% vs. 16.3%), statin therapy (40% vs. 16.9%), left ventricular systolic dysfunction (33.3% vs. 17.5%) (paspirin combination were concomitant vascular disease, diabetes, and (younger) age in patients with AF and were concomitant AF and male sex in patients with MHV. Interestingly, the incidence of combination therapy was found to increase with a higher HAS-BLED score in both patients with AF and MHV (paspirin was found to be prescribed to patients with AF mainly for the prevention of cardiovascular events, for which warfarin monotherapy usually suffices. On the other hand, co-treatment with aspirin appeared to be underused in patients with MHV.

  9. [On the history of vitamin K, dicoumarol and warfarin].

    Science.gov (United States)

    Norn, Svend; Permin, Henrik; Kruse, Edith; Kruse, Poul R

    2014-01-01

    The history of the discovery and development of vitamin K and its antagonists, the oral anticoagulants dicoumarol and warfarin, are fascinating, triumphant landmarks in the annals of medicine. Vitamin K was found by Carl Peter Henrik Dam and Fritz Schønheyder from the University of Copenhagen. The discovery was initiated by Dam, by a lucky choice of chicks in the dissertation of sterol metabolism, since the vitamin is not formed by intestinal bacteria in these animals. In these experiments the lack of an unknown factor in the synthetic diet caused internal bleeding similar to that found in scurvy, but the bleeding was not reversed by vitamin C and it could not be explained by the lack of classical vitamins. In 1935 the unknown antihaemorrhagic factor was named vitamin K and a few months later the phenomenon was also observed by H.J. Almquist and E.L.R. Stokstad in Berkeley. The activity of the factor was determined by bioassay in different extracts of green vegetables and alfalfa by Dam and Schønheyder. Vitamin K was isolated in 1939 by Dam and Paul Karrer in Zurich and the structure was determined by Edward Adelbert Doisy. Dam and Doisy were awarded the Nobel Prize in 1943. A dramatic story starts the discovery of dicoumarol. In the 1920s cattle in Canada began dying of internal bleeding with no obvious precipitating cause. Frank W. Schofield, a veterinary pathologist in Alberta, found that the mysterious disease was connected to the consumption of spoiled sweet clover hay and noted a prolonged clotting time. Ten years after a farmer traveled in a blizzard with his dead cow and a milk can of the unclotted blood to the University of Wisconsin. Only the door to the biochemical department of Karl Paul Link was open. This event started the isolation of the anticoagulant agent dicou- marol which was formed by microbial induced oxidation of coumarin in the mouldy sweet clover hay. More than hundred dicoumarol-like anticoagulants were synthesized by Link and his co

  10. SU-F-J-221: Adjusted Dose and Its Relation to Radiation Induced Liver Disease During Hepatocellular Carcinoma Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huang, P; Gang, Y; Qin, S; Li, D [Shandong Province Key Laboratory of Medical Physics and Image Processing Technology, School of Physics and Electronics, Shandong Normal University (China); Li, H; Chen, J; Ma, C; Yin, Y [Department of Radiation Oncology, Shandong Cancer Hospital and Institute (China)

    2016-06-15

    Purpose: Many patients with hepatocellular carcinoma (HCC) had hepatic anatomy variations as a result of inter-fraction deformation during fractionated radiotherapy, which may result in difference from the planned dose. This study aimed to investigate the relationship between adjusted dose and radiation induced liver disease (RILD) in HCC patients receiving three dimensional conformal radiotherapy (3DCRT). Methods: Twenty-three HCC patients received conventional fractionated 3DCRT were enrolled in this retrospective investigation. Among them, seven patients had been diagnosed of RILD post-radiotherapy, including 4 cases of grade 2, 3 cases of grade 3 according to the CTCAE Version 3.0. Daily cone-beam CT (CBCT) scans were acquired throughout the whole treatment course for each patient. To reconstruct the daily dose to a patient considering the interfraction anatomy variations, the planned beams from each patient’s treatment plan were firstly applied to each daily modified CBCT (mCBCT). The daily doses were then summed together with the help of deformable image registration (DIR) to obtain the adjusted dose (Dadjusted) of the patient. Finally, the dose changes in normal liver between planned dose (Dplan) and Dadjusted were evaluated by V20, V30, V40 and the mean dose to normal liver (MDTNL). Univariate analysis was performed to identify the significant dose changes. Results: Among the twenty-three patients, the adjusted liver V20, V30, V40 and MDTNL showed significant changes from the planned ones (p<0.05) and averagely increased by 4.1%, 4.7%, 4.5% and 3.9Gy, respectively. And the adjusted liver dose in twenty-one patients (91%) were higher than planned value, the adjusted dose of patients with RILD (6/7) exceeds to the hepatic radiation tolerance. Conclusion: The adjusted dose of all the studied patients significantly differs from planned dose, and mCBCT-based dose reconstruction can aid in evaluating the robustness of the planning solutions, and adjusted dose

  11. Association between warfarin combined with serotonin-modulating antidepressants and increased case fatality in primary intracerebral hemorrhage: a population-based study.

    Science.gov (United States)

    Löppönen, Pekka; Tetri, Sami; Juvela, Seppo; Huhtakangas, Juha; Saloheimo, Pertti; Bode, Michaela K; Hillbom, Matti

    2014-06-01

    Patients receiving oral anticoagulants run a higher risk of cerebral hemorrhage with a poor outcome. Serotonin-modulating antidepressants (selective serotonin reuptake inhibitors [SSRIs], serotonin-norepinephrine reuptake inhibitors [SNRIs]) are frequently used in combination with warfarin, but it is unclear whether this combination of drugs influences outcome after primary intracerebral hemorrhage (PICH). The authors investigated case fatality in PICH among patients from a defined population who were receiving warfarin alone, with aspirin, or with serotonin-modulating antidepressants. Nine hundred eighty-two subjects with PICH were derived from the population of Northern Ostrobothnia, Finland, for the years 1993-2008, and those with warfarin-associated PICH were eligible for analysis. Their hospital records were reviewed, and medication data were obtained from the national register of prescribed medicines. Kaplan-Meier survival curves were drawn to illustrate cumulative case fatality, and a Cox proportional-hazards analysis was performed to demonstrate predictors of death. Of the 176 patients eligible for analysis, 17 had been taking aspirin and 19 had been taking SSRI/SNRI together with warfarin. The 30-day case fatality rates were 50.7%, 58.8%, and 78.9%, respectively, for those taking warfarin alone, with aspirin, or with SSRI/SNRI (p = 0.033, warfarin plus SSRI/SNRI compared with warfarin alone). Warfarin combined with SSRI/SNRI was a significant independent predictor of case fatality (adjusted HR 2.10, 95% CI 1.13-3.92, p = 0.019). Concurrent use of warfarin and a serotonin-modulating antidepressant, relative to warfarin alone, seemed to increase the case fatality rate for PICH. This finding should be taken into account if hematoma evacuation is planned.

  12. Sol-gel Derived Warfarin - Silica Composites for Controlled Drug Release.

    Science.gov (United States)

    Dolinina, Ekaterina S; Parfenyuk, Elena V

    2017-01-01

    Warfarin, commonly used anticoagulant in clinic, has serious shortcomings due to its unsatisfactory pharmacodynamics. One of the efficient ways for the improvement of pharmacological and consumer properties of drugs is the development of optimal drug delivery systems. The aim of this work is to synthesize novel warfarin - silica composites and to study in vitro the drug release kinetics to obtain the composites with controlled release. The composites of warfarin with unmodified (UMS) and mercaptopropyl modified silica (MPMS) were synthesized by sol-gel method. The composite formation was confirmed by FTIR spectra. The concentrations of warfarin released to media with pH 1.6, 6.8 and 7.4 were measured using UV spectroscopy. The drug release profiles from the solid composites were described by a series of kinetic models which includes zero order kinetics, first order kinetics, the modified Korsmeyer-Peppas model and Hixson-Crowell model. The synthesized sol-gel composites have different kinetic behavior in the studied media. In contrast to the warfarin composite with unmodified silica, the drug release from the composite with mercaptopropyl modified silica follows zero order kinetics for 24 h irrespective to the release medium pH due to mixed mechanism (duffusion + degradation and/or disintegration of silica matrix). The obtained results showed that warfarin - silica sol-gel composites have a potential application for the development of novel oral formulation of the drug with controlled delivery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. The impact of peritransplant warfarin use on renal transplant outcome.

    LENUS (Irish Health Repository)

    Connaughton, Dervla M

    2011-03-31

    The unplanned nature of kidney transplantation necessitates that patients undergo surgery without prior cessation of warfarin. Our study analyses the impact of warfarin treatment in the peritransplant period on graft outcome and perioperative transfusion requirements.

  14. An interaction between warfarin and cannabidiol, a case report

    OpenAIRE

    Grayson, Leslie; Vines, Brannon; Nichol, Kate; Szaflarski, Jerzy P.

    2017-01-01

    Highlights • An interaction between warfarin and cannabidiol is described • The mechanisms of cannabidiol and warfarin metabolism are reviewed • Mechanism of the interaction is proposed • INR should be monitored in patients when cannabinoids are introduced

  15. Generic switching of warfarin and risk of excessive anticoagulation

    DEFF Research Database (Denmark)

    Hellfritzsch, Maja; Rathe, Jette; Stage, Tore Bjerregaard

    2016-01-01

    PURPOSE: Generic switching of warfarin was recently repealed in Denmark, as adverse drug reaction (ADR) reports suggested risk of excessive anticoagulation following switches from branded to generic warfarin. We investigated this putative association in a formalized pharmacoepidemiological analys...

  16. Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran.

    Science.gov (United States)

    Kolb, Jennifer M; Flack, Kathryn Friedman; Chatterjee-Murphy, Prapti; Desai, Jay; Wallentin, Lars C; Ezekowitz, Michael; Connolly, Stuart; Reilly, Paul; Brueckmann, Martina; Ilgenfritz, John; Aisenberg, James

    2018-03-27

    Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.

  17. Intramural duodenal hematoma as a complication of therapy with Warfarin: a case report and literature review; Hematoma intramural duodenal como complicacao de terapia anticoagulante com Warfarin: relato de caso e revisao da literatura

    Energy Technology Data Exchange (ETDEWEB)

    Faria, Juliano [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Dept. de Diagnostico por Imagem]. E-mail: drjuliano@uol.com.br; Pessoa, Roberta; Hudson, Marcelo; Vitoi, Silvio; Villela, Ovidio; Torres, Jose; Paula, Mara Delgado [Hospital Marcio Cunha, Ipatinga, MG (Brazil). Servico de Diagnostico por Imagem; Bemvindo, Aloisio [Hospital Marcio Cunha, Ipatinga, MG (Brazil). Servico de Terapia Intensiva

    2004-12-01

    We report a case of a patient receiving chronic oral anticoagulant therapy with Warfarin who presented with acute intestinal obstruction. Computed tomography showed intramural duodenal hematoma. Treatment was conservative with correction of the coagulation parameters and observation. This case exemplifies the usefulness of conservative therapy and computed tomography in patients with acute small bowel obstruction receiving anticoagulant therapy. (author)

  18. 12/15-Lipoxygenase Inhibition or Knockout Reduces Warfarin-Associated Hemorrhagic Transformation After Experimental Stroke.

    Science.gov (United States)

    Liu, Yu; Zheng, Yi; Karatas, Hulya; Wang, Xiaoying; Foerch, Christian; Lo, Eng H; van Leyen, Klaus

    2017-02-01

    For stroke prevention, patients with atrial fibrillation typically receive oral anticoagulation. The commonly used anticoagulant warfarin increases the risk of hemorrhagic transformation (HT) when a stroke occurs; tissue-type plasminogen activator treatment is therefore restricted in these patients. This study was designed to test the hypothesis that 12/15-lipoxygenase (12/15-LOX) inhibition would reduce HT in warfarin-treated mice subjected to experimental stroke. Warfarin was dosed orally in drinking water, and international normalized ratio values were determined using a Coaguchek device. C57BL6J mice or 12/15-LOX knockout mice were subjected to transient middle cerebral artery occlusion with 3 hours severe ischemia (model A) or 2 hours ischemia and tissue-type plasminogen activator infusion (model B), with or without the 12/15-LOX inhibitor ML351. Hemoglobin was determined in brain homogenates, and hemorrhage areas on the brain surface and in brain sections were measured. 12/15-LOX expression was detected by immunohistochemistry. Warfarin treatment resulted in reproducible increased international normalized ratio values and significant HT in both models. 12/15-LOX knockout mice suffered less HT after severe ischemia, and ML351 reduced HT in wild-type mice. When normalized to infarct size, ML351 still independently reduced hemorrhage. HT after tissue-type plasminogen activator was similarly reduced by ML351. In addition to its benefits in infarct size reduction, 12/15-LOX inhibition also may independently reduce HT in warfarin-treated mice. ML351 should be further evaluated as stroke treatment in anticoagulated patients suffering a stroke, either alone or in conjunction with tissue-type plasminogen activator. © 2017 American Heart Association, Inc.

  19. Study protocol for the dabigatran, apixaban, rivaroxaban, edoxaban, warfarin comparative effectiveness research study.

    Science.gov (United States)

    Krumme, Alexis A; Pawar, Ajinkya; Schneeweiss, Sebastian; Glynn, Robert J; Choudhry, Niteesh K; Kulldorff, Martin; Ortiz, Adrian Santiago; Avorn, Jerome; Gagne, Joshua J

    2018-01-01

    Since 2010, four oral anticoagulants have been approved for marketing in addition to warfarin for treatment of thromboembolic disease. Limited head-to-head data exist comparing these treatments, leaving patients and clinicians with little guidance for selecting a strategy that balances recurrence reduction with bleeding risk. In the dabigatran, apixaban, rivaroxban, edoxaban and warfarin comparative effectiveness research study, we compare all five currently available oral anticoagulant agents for the extended treatment of deep venous thrombosis and pulmonary embolism, as well as no extended treatment, and evaluate whether results differ in specific sub-populations. As our population includes Medicare novel anticoagulant users and large numbers of commercially insured and Medicaid patients, our results will likely be transportable to the majority of US patients experiencing a DVT or pulmonary embolism. NCT03271450.

  20. Population Impact of Drug Interactions with Warfarin

    DEFF Research Database (Denmark)

    Martín-Pérez, Mar; Gaist, David; de Abajo, Francisco J

    2018-01-01

    OBJECTIVE:  To investigate the population impact of previously reported interactions between warfarin and other drugs on international normalized ratio (INR) levels. METHODS:  Using The Health Improvement Network (THIN), a United Kingdom primary care database, a cohort of warfarin users between...... 2005 and 2013 (N = 121,962) was followed until the first qualifying prescription for the potential interacting drugs was evaluated. Sixteen sub-cohorts, one for each study drug, and a control sub-cohort of warfarin were ascertained. Short-term changes in INR levels were assessed by comparing INR values...... measured before and after initiation of the interacting drug with paired Student's t-test. We also evaluated the proportion of patients with INR values outside the therapeutic range (INR: 2-3). RESULTS:  Miconazole use was associated with the highest mean increase in INR (+3.35), followed by amiodarone (+1...

  1. Pionerer bag vitamin K, dikumarol og warfarin

    DEFF Research Database (Denmark)

    Norn, Svend; Permin, Henrik; Kruse, Edith

    2014-01-01

    was determined by bioassay in different extracts of green vegetables and alfalfa by Dam and Schønheyder. Vitamin K was isolated in 1939 by Dam and Paul Karrer in Zurich and the structure was determined by Edward Adelbert Doisy. Dam and Doisy were awarded the Nobel Prize in 1943. A dramatic story starts...... by microbial induced oxidation of coumarin in the mouldy sweet clover hay. More than hundred dicoumarol-like anticoagulants were synthesized by Link and his co-workers. A potent hemorrhagic agent named warfarin was first used as an effective rat poison. However, warfarin became the drug of choice and the break...

  2. Warfarin-Associated Diaphragmatic Hernia: An Unusual Diagnosis

    Directory of Open Access Journals (Sweden)

    Cristina Vilhena

    2015-01-01

    Full Text Available Fetal warfarin syndrome is a consequence of maternal intake of warfarin during pregnancy and comprises a wide range of manifestations, including some typical facial dysmorphologic features. The authors report a case of prenatal ultrasonographic diagnosis of warfarin embryopathy in an obese woman on unsupervised warfarin prophylaxis at the 16th week of gestation. The fetus presented with facial dysmorphism, pectus excavatum, diaphragmatic hernia, and pulmonary hypoplasia. To the best of our knowledge, this is the second reported case of warfarin-associated diaphragmatic hernia.

  3. NPC1L1 is a key regulator of intestinal vitamin K absorption and a modulator of warfarin therapy.

    Science.gov (United States)

    Takada, Tappei; Yamanashi, Yoshihide; Konishi, Kentaro; Yamamoto, Takehito; Toyoda, Yu; Masuo, Yusuke; Yamamoto, Hideaki; Suzuki, Hiroshi

    2015-02-18

    Vitamin K (VK) is a micronutrient that facilitates blood coagulation. VK antagonists, such as warfarin, are used in the clinic to prevent thromboembolism. Because VK is not synthesized in the body, its intestinal absorption is crucial for maintaining whole-body VK levels. However, the molecular mechanism of this absorption is unclear. We demonstrate that Niemann-Pick C1-like 1 (NPC1L1) protein, a cholesterol transporter, plays a central role in intestinal VK uptake and modulates the anticoagulant effect of warfarin. In vitro studies using NPC1L1-overexpressing intestinal cells and in vivo studies with Npc1l1-knockout mice revealed that intestinal VK absorption is NPC1L1-dependent and inhibited by ezetimibe, an NPC1L1-selective inhibitor clinically used for dyslipidemia. In addition, in vivo pharmacological studies demonstrated that the coadministration of ezetimibe and warfarin caused a reduction in hepatic VK levels and enhanced the pharmacological effect of warfarin. Adverse events caused by the coadministration of ezetimibe and warfarin were rescued by oral VK supplementation, suggesting that the drug-drug interaction effects observed were the consequence of ezetimibe-mediated VK malabsorption. This mechanism was supported by a retrospective evaluation of clinical data showing that, in more than 85% of warfarin-treated patients, the anticoagulant activity was enhanced by cotreatment with ezetimibe. Our findings provide insight into the molecular mechanism of VK absorption. This new drug-drug interaction mechanism between ezetimibe (a cholesterol transport inhibitor) and warfarin (a VK antagonist and anticoagulant) could inform clinical care of patients on these medications, such as by altering the kinetics of essential, fat-soluble vitamins. Copyright © 2015, American Association for the Advancement of Science.

  4. Comparative metabolism of warfarin in rats and chickens.

    Science.gov (United States)

    Saengtienchai, A; Ikenaka, Y; Watanabe, K; Ishida, T; Ishizuka, M

    2011-12-01

    Warfarin, a coumarin rodenticide, is commonly used worldwide for rodent control, and is often reported as the cause for poisoning accidents in nontarget animals, in particular bird species. However, the metabolism of warfarin in birds is still unclear. In a previous study, we found an unknown warfarin metabolite in chicken cytosolic fractions. In the present study, we aimed to clarify the cytosolic warfarin metabolites in chickens compared with those in rats. The cytosol fractions of both chicken and rat livers showed the metabolic activity of 2 diastereomers and 2 enantiomers of warfarin alcohol. In chicken cytosol, we found that the production level of (S)-warfarin-(S)-alcohol was markedly higher (32-fold) than that in rat cytosol. From the results of the inhibition assay, we finally suggest that aldehyde oxidase may mainly contribute to the warfarin alcohol products in chicken cytosol.

  5. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF.

    Science.gov (United States)

    Hankey, Graeme J; Patel, Manesh R; Stevens, Susanna R; Becker, Richard C; Breithardt, Günter; Carolei, Antonio; Diener, Hans-Christoph; Donnan, Geoffrey A; Halperin, Jonathan L; Mahaffey, Kenneth W; Mas, Jean-Louis; Massaro, Ayrton; Norrving, Bo; Nessel, Christopher C; Paolini, John F; Roine, Risto O; Singer, Daniel E; Wong, Lawrence; Califf, Robert M; Fox, Keith A A; Hacke, Werner

    2012-04-01

    In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08

  6. Prediction of warfarin maintenance dose in Han Chinese patients using a mechanistic model based on genetic and non-genetic factors.

    Science.gov (United States)

    Lu, Yuan; Yang, Jinbo; Zhang, Haiyan; Yang, Jin

    2013-07-01

    Many attempts have been made to predict the warfarin maintenance dose in patients beginning warfarin therapy using a descriptive model based on multiple linear regression. Here we report the first attempt to develop a comprehensive mechanistic model integrating in vitro-in vivo extrapolation (IVIVE) with a pharmacokinetic-pharmacodynamic model to predict the warfarin maintenance dose in Han Chinese patients. The model incorporates demographic factors [sex, age, body weight (BW)] and the genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1). Information on the various factors, mean warfarin daily dose and International Normalized Ratio (INR) was available for a cohort of 197 Han Chinese patients. Based on in vitro enzyme kinetic parameters for S-warfarin metabolism, demographic data for Han Chinese and some scaling factors, the S-warfarin clearance (CL) was predicted for patients in the cohort with different CYP2C9 genotypes using IVIVE. The plasma concentration of S-warfarin after a single oral dose was simulated using a one-compartment pharmacokinetic model with first-order absorption and a lag time and was combined with a mechanistic coagulation model to simulate the INR response. The warfarin maintenance dose was then predicted based on the demographic data and genotypes of CYP2C9 and VKORC1 for each patient and using the observed steady-state INR (INRss) as a target value. Finally, sensitivity analysis was carried out to determine which factor(s) affect the warfarin maintenance dose most strongly. The predictive performance of this mechanistic model is not inferior to that of our previous descriptive model. There were significant differences in the mean warfarin daily dose in patients with different CYP2C9 and VKORC1 genotypes. Using IVIVE, the predicted mean CL of S-warfarin for patients with CYP2C9*1/*3 (0.092 l/h, n = 11) was 57 % less than for those with wild-type *1/*1 (0.215 l/h, n

  7. Comparison of warfarin sensitivity between rat and bird species

    OpenAIRE

    Watanabe, Kensuke P.; Saengtienchai, Aksorn; Tanaka, Kazuyuki D.; Ikenaka, Yoshinori; Ishizuka, Mayumi

    2010-01-01

    Scattering coumarin-derivative rodenticides in broad areas have caused primary- and secondary-poisoning incidents in non-target wild birds. In this study, we compared factors determining warfarin sensitivity between bird species and rats based on vitamin K 2,3-epoxide reductase (VKOR) kinetics, VKOR inhibition by warfarin and warfarin metabolism assays. In VKOR characterization, chickens and ostriches showed significantly lower enzymatic efficiencies than rats (one-sixth and one-third, respec...

  8. Association with polymorphic marmoset cytochrome P450 2C19 of in vivo hepatic clearances of chirally separated R-omeprazole and S-warfarin using individual marmoset physiologically based pharmacokinetic models.

    Science.gov (United States)

    Kusama, Takashi; Toda, Akiko; Shimizu, Makiko; Uehara, Shotaro; Inoue, Takashi; Uno, Yasuhiro; Utoh, Masahiro; Sasaki, Erika; Yamazaki, Hiroshi

    2017-11-10

    1. Simulated clearances of R-warfarin and efavirenz were recently reported for individual cynomolgus monkeys genotyped for cytochrome P450 2C19 and 2C9, respectively. To expand and verify this modeling procedure, simulations of R/S-omeprazole and R/S-warfarin clearances after oral administrations in individual marmosets were performed using individual simplified physiologically based pharmacokinetic (PBPK) modeling consisting of gut, liver and central compartments. 2. Pharmacokinetics of R/S-omeprazole were chirally determined using the previously reported plasma microsamples in this study. The areas under the plasma concentration/time curves (AUC) of R-omeprazole and S-warfarin, but not S-omeprazole and R-warfarin, after oral administrations in the P450 2C19 homozygous mutant group were significantly higher than those in the wild-type group. These modeled hepatic intrinsic clearances were also significantly associated with the marmoset P450 2C19 genotypes. Other parameter values, e.g. absorption rate constants or systemic circulation volumes, were not likely determining factors. 3. The reported individual AUC values measured in 4-6 marmosets after oral R-omeprazole and S-warfarin administrations were significantly correlated with the AUC values predicted using the PBPK models after virtual administrations. 4. This study indicates that clearances of R-omeprazole, S-warfarin and related medicines associated with polymorphic P450 2C19 in individual marmosets can be simulated using simplified individual PBPK models.

  9. Optimal initial dose adjustment of warfarin in orthopedic patients.

    Science.gov (United States)

    Lenzini, Petra A; Grice, Gloria R; Milligan, Paul E; Gatchel, Susan K; Deych, Elena; Eby, Charles S; Burnett, R Stephen J; Clohisy, John C; Barrack, Robert L; Gage, Brian F

    2007-11-01

    Warfarin sodium is commonly prescribed for the prophylaxis and treatment of venous thromboembolism. Dosing algorithms have not been widely adopted because they require a fixed initial warfarin dose (eg, 5 mg) and are not tailored to other factors that may affect the international normalized ratio (INR). To develop an algorithm that could predict a therapeutic warfarin dose based on drug interactions, INR response after the initial warfarin doses, and other clinical factors. We used stepwise regression to quantify the relationship between these factors in patients beginning prophylactic warfarin therapy immediately prior to joint replacement. In the derivation cohort (n = 271), we separately modeled the therapeutic dose after 2 and 3 initial doses. We prospectively validated these 2 models in an independent cohort (n = 105). About half of the therapeutic dose variability was predictable after 3 days of therapy: R2 was 53% in the derivation cohort and 42% in the validation cohort. INR response after 3 warfarin doses (INR3) inversely correlated with therapeutic dose (p < 0.001). Intraoperative blood loss transiently, but significantly, elevated the postoperative INR values. Other significant (p < 0.03) predictors were the first and second warfarin doses (+7% and +6%, respectively, per 1 mg), and statin use (-15.0%). The model derived after 2 warfarin doses explained 32% of the variability in therapeutic dose. We developed and validated algorithms that estimate therapeutic warfarin doses based on clinical factors and INR response available after 2-3 days of warfarin therapy. The algorithms are implemented online at www.WarfarinDosing.org.

  10. Hospital Admissions, Costs, and 30-Day Readmissions Among Newly Diagnosed Nonvalvular Atrial Fibrillation Patients Treated with Dabigatran Etexilate or Warfarin.

    Science.gov (United States)

    Fonseca, Eileen; Sander, Stephen D; Hess, Gregory P; Ghosh, Sabyasachi

    2015-11-01

    Oral anticoagulation such as warfarin and dabigatran is indicated for atrial fibrillation (AF) patients at risk of ischemic stroke. Dabigatran etexilate was developed to address the limitations of warfarin, including the need for regular blood monitoring, which has the potential to lead to higher health care resource use, particularly in hospitalized patients. To evaluate whether hospitalization cost, length of hospital stay (LOS), likelihood of readmission within 30 days, and cost of readmissions differed across inpatient encounters among nonvalvular atrial fibrillation (NVAF) patients that were newly diagnosed and newly treated with either dabigatran or warfarin. A retrospective cohort study was conducted using IMS Health's Charge Detail Master (CDM) database. Hospitalizations were identified based on a primary or secondary AF diagnosis, dabigatran or warfarin use, and a discharge date from January 2011 through March 2012. The identified patients without valvular procedures and transient AF were required to have a minimum of 12 months of pharmacy and private practitioner records prior to the inpatient encounter to ensure that they were newly treated on dabigatran or warfarin. Propensity score matching was used to balance baseline characteristics between treatment cohorts. Outcomes assessed were LOS, 30-day readmissions, and costs. Because individual patients could have more than 1 hospital observation, generalized estimating equations (GEE) with a gamma distribution (log link) were used for the analysis of continuous outcome measures (e.g., LOS and costs) and a binominal distribution for dichotomous outcomes (hospital readmissions). Two cohorts were propensity score matched (1:2) on demographic and clinical characteristics. The dabigatran cohort included 646 hospitalizations, and the warfarin cohort included 1,292 hospitalizations. Hospitalizations were on average 13% shorter (4.8 vs. 5.5 days, P  less than  0.001) and cost 12% less ($14,794 vs. $16,826, P

  11. Hematoma intramural duodenal como complicação de terapia anticoagulante com Warfarin: relato de caso e revisão da literatura Intramural duodenal hematoma as a complication of therapy with Warfarin: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Juliano Faria

    2004-12-01

    Full Text Available Relatamos o caso de uma paciente em terapia anticoagulante oral com Warfarin, apresentando obstrução intestinal aguda. A tomografia computadorizada revelou hematoma intramural duodenal. O tratamento baseou-se na correção das provas de coagulação e medidas expectantes. Este caso ilustra o valor da tomografia computadorizada e da abordagem conservadora nos pacientes em terapia anticoagulante com obstrução aguda do intestino delgado.We report a case of a patient receiving chronic oral anticoagulant therapy with Warfarin who presented with acute intestinal obstruction. Computed tomography showed intramural duodenal hematoma. Treatment was conservative with correction of the coagulation parameters and observation. This case exemplifies the usefulness of conservative therapy and computed tomography in patients with acute small bowel obstruction receiving anticoagulant therapy.

  12. oral

    African Journals Online (AJOL)

    Chlorhexidine 0,2% gluconate is used as a mouth rinse and is an effective antibacterial agent. Its primary side- effects are staining of the teeth and the oral mucosa, particularly the dorsal surface of the tongue. However, this is transient. It has been shown to be effective as a prophylactic agent in preventing oral candidosis in ...

  13. Warfarin use in hemodialysis patients: what is the risk?

    LENUS (Irish Health Repository)

    Phelan, P J

    2012-02-01

    BACKGROUND: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. METHODS: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. RESULTS: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). CONCLUSIONS: This study confirms the higher bleeding risk associated with HD\\/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. SUMMARY: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A

  14. Warfarin use in hemodialysis patients: what is the risk?

    LENUS (Irish Health Repository)

    Phelan, P J

    2011-03-01

    Background: There is a paucity of data concerning the risks associated with warfarin in hemodialysis (HD) patients. We compared major bleeding episodes in this group with HD patients not receiving warfarin and with a cohort of non-HD patients receiving warfarin. Methods: A retrospective review of 141 HD patients on warfarin (HDW), 704 HD patients not on warfarin (HDNW) and 3,266 non-dialysis warfarin patients (NDW) was performed. Hospital admissions for hemorrhagic events and ischemic strokes were examined as was hospital length of stay and blood product use. INR variability was also assessed. Results: The incidence rates for major hemorrhage per 100 patient years was 10.8 in the HDW group as compared to 8.0 in the HDNW (p = 0.593) and 2.1 in the NDW (p < 0.001) groups. Mean units of red blood cell transfusions required was higher in patients on dialysis with no significant difference between HDW and HDNW groups. The risk of ischemic stroke per 100 patient years was 1.7 in the HDW group as compared to 0.7 in the HDNW groups (p = 0.636) and 0.4 in the NDW (p = 0.003). The HDW group had higher inter-measurement INR variability compared to the NDW group (p = 0.034). In patients with atrial fibrillation, HDW group had a higher incidence of ischemic stroke than the NDW group (2.2 versus 0.4 events per 100 patient years; p = 0.024). Conclusions: This study confirms the higher bleeding risk associated with HD\\/ESRD but suggests that warfarin use in these patients may not add significantly to this risk. We also demonstrated high rates of ischemic stroke in HD patients despite warfarin use. Summary: Our study compares the frequency of major hemorrhage and secondarily, ischemic stroke in HD patients receiving or not receiving warfarin, with non-HD patients receiving warfarin. The major finding was that frequency of hemorrhage was higher in HD patients receiving warfarin than in non-HD patients receiving warfarin, but not different in HD patients with or without warfarin. A

  15. Validation of a proposed warfarin dosing algorithm based on the genetic make-up of Egyptian patients.

    Science.gov (United States)

    Ekladious, Sherif M M; Issac, Marianne Samir M; El-Atty Sharaf, Sahar Abd; Abou-Youssef, Hazem S

    2013-12-01

    Warfarin is the most frequently prescribed oral anticoagulant worldwide. Due to its narrow therapeutic index and inter-patient variability in dose requirement, this drug has been considered an ideal target for personalised medicine. Several warfarin dosing algorithms have been proposed to tailor the warfarin dosage in the European, Asian and African-American populations. However, minimal interest was directed towards Middle East countries. The factors affecting warfarin dose requirement could be different in patients from different geographical and ethnic groups, limiting the value of published dosing algorithms. The first objective of this study was to examine the contribution of genetic and nongenetic factors on the variability of warfarin dose requirements in the Egyptian population using an easy, cost-effective and rapid analysis of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 (CYP) 2C9 single nucleotide polymorphism (SNP) genotyping of patients. A second objective was to develop and validate an algorithm for warfarin dose prediction that is tailored to Egyptian patients. Eighty-four patients, 41 males and 43 females, with a median (25th-75th percentiles) age of 39 (31-48) years were recruited in this study. Fifty patients whose international normalised ratio (INR) was in the range of 2-3 were allocated to a study cohort. SYBR Green-based multiplex allele-specific real-time PCR was used for genotyping of CYP2C9 (1075A>C) and VKORC1 (1173C>T) polymorphisms. Linear regression analysis, including the variables age, gender, CYP2C9 and VKORC1 SNP genotypes, was run to derive the best model for estimating the warfarin dose that achieves an INR of 2-3. The new warfarin dosing algorithm was examined in a second cohort of patients (n=34) to check its validity. The predicted dose requirements for a subgroup of our patients were calculated according to Gage and International Warfarin Pharmacogenetics Consortium (IWPC) algorithms available at

  16. Comparison of warfarin sensitivity between rat and bird species.

    Science.gov (United States)

    Watanabe, Kensuke P; Saengtienchai, Aksorn; Tanaka, Kazuyuki D; Ikenaka, Yoshinori; Ishizuka, Mayumi

    2010-06-01

    Scattering coumarin derivative rodenticides in broad areas have caused primary- and secondary-poisoning incidents in non-target wild birds. In this study, we compared factors determining warfarin sensitivity between bird species and rats based on vitamin K 2,3-epoxide reductase (VKOR) kinetics, VKOR inhibition by warfarin and warfarin metabolism assays. In VKOR characterization, chickens and ostriches showed significantly lower enzymatic efficiencies than rats (one-sixth and one-third, respectively), suggesting bird species depend more on a non-VKOR vitamin K source. On the other hand, the inhibition constants (K(i)) of VKOR for warfarin were significantly different between chickens and ostriches (11.3+/-2.5 microM and 0.64+/-0.39 microM, respectively). Interestingly, the ostrich K(i) was similar to the values for rats (0.28+/-0.09 microM). The K(i) results reveal a surprising possibility that VKOR in some bird species are easily inhibited by warfarin. Warfarin metabolism assays also showed a large inter-species difference in bird species. Chickens and ostriches showed higher metabolic activity than that of rats, while mallards and owls showed only a slight ability to metabolize warfarin. In this study, we clarified the wide inter-species difference that exists among birds in xenobiotic metabolism and sensitivity to a rodenticide. Copyright 2010 Elsevier Inc. All rights reserved.

  17. A comparison of warfarin utilisation in North America and Ireland

    Directory of Open Access Journals (Sweden)

    Hussein Haji

    2014-01-01

    Full Text Available Background: The objective of this study was to compare warfarin utilisation trends in Canada, the United States, and Ireland between January 2005 and September 2011. Materials and Methods: We conducted a population-based cross-sectional time series analysis of warfarin utilisation data from January 2005 to September 2011 in the United States, Canada, and Ireland to examine differences in temporal trends in warfarin utilisation. Results: A nearly 50% higher warfarin utilisation rate was observed in Canada and Ireland relative to the United States - the average monthly warfarin utilisation rate was approximately 626 units per 1,000 people in Canada, 423 units per 1,000 people in the United States, and 630 units per 1,000 people in Ireland. However, relative rates of growth in warfarin utilisation were 25.1%, 15.3%, and 38.3% for the United States, Canada, and Ireland, respectively. Interpretation: Rates of warfarin utilisation differ considerably and geographically as evidenced by utilisation rates in the United States, Canada, and Ireland.

  18. Safety and efficacy of rivaroxaban compared with warfarin in patients undergoing peripheral arterial procedures.

    Science.gov (United States)

    Talukdar, Anjan; Wang, S Keisin; Czosnowski, Lauren; Mokraoui, Nassim; Gupta, Alok; Fajardo, Andres; Dalsing, Michael; Motaganahalli, Raghu

    2017-10-01

    Rivaroxaban is a United States Food and Drug Administration-approved oral anticoagulant for venous thromboembolic disease; however, there is no information regarding the safety and its efficacy to support its use in patients after open or endovascular arterial interventions. We report the safety and efficacy of rivaroxaban vs warfarin in patients undergoing peripheral arterial interventions. This single-institution retrospective study analyzed all sequential patients from December 2012 to August 2014 (21 months) who were prescribed rivaroxaban or warfarin after a peripheral arterial procedure. Our study population was then compared using American College of Chest Physicians guidelines with patients then stratified as low, medium, or high risk for bleeding complications. Statistical analyses were performed using the Student t-test and χ 2 test to compare demographics, readmissions because of bleeding, and the need for secondary interventions. Logistic regression models were used for analysis of variables associated with bleeding complications and secondary interventions. The Fisher exact test was used for power analysis. There were 44 patients in the rivaroxaban group and 50 patients in the warfarin group. Differences between demographics and risk factors for bleeding between groups or reintervention rate were not statistically significant (P = .297). However, subgroup evaluation of the safety profile suggests that patients who were aged ≤65 years and on warfarin had an overall higher incidence of major bleeding (P = .020). Patients who were aged >65 years, undergoing open operation, had a significant risk for reintervention (P = .047) when they received rivaroxaban. Real-world experience using rivaroxaban and warfarin in patients after peripheral arterial procedures suggests a comparable safety and efficacy profile. Subgroup analysis of those requiring an open operation demonstrated a decreased bleeding risk when rivaroxaban was used (in those aged <65

  19. Meta-analysis of randomized controlled trials on risk of myocardial infarction from the use of oral direct thrombin inhibitors

    DEFF Research Database (Denmark)

    Artang, Ramin; Rome, Eric; Nielsen, Jørn Dalsgaard

    2013-01-01

    . To address these questions, we systematically searched MEDLINE and performed a meta-analysis on randomized trials that compared oral DTIs with warfarin for any indication with end point of MIs after randomization. We furthermore performed a secondary meta-analysis on atrial fibrillation stroke prevention...... trials with alternative anticoagulants compared with warfarin with end point of MIs after randomization. A total of 11 trials (39,357 patients) that compared warfarin to DTIs (dabigatran, ximelagatran, and AZD0837) were identified. In these trials, patients treated with oral DTIs were more likely......Dabigatran has been associated with greater risk of myocardial infarction (MI) than warfarin. It is unknown whether the increased risk is unique to dabigatran, an adverse effect shared by other oral direct thrombin inhibitors (DTIs), or the result of a protective effect of warfarin against MI...

  20. Outcomes Associated With Resuming Warfarin Treatment After Hemorrhagic Stroke or Traumatic Intracranial Hemorrhage in Patients With Atrial Fibrillation.

    Science.gov (United States)

    Nielsen, Peter Brønnum; Larsen, Torben Bjerregaard; Skjøth, Flemming; Lip, Gregory Y H

    2017-04-01

    The increase in the risk for bleeding associated with antithrombotic therapy causes a dilemma in patients with atrial fibrillation (AF) who sustain an intracranial hemorrhage (ICH). A thrombotic risk is present; however, a risk for serious harm associated with resumption of anticoagulation therapy also exists. To investigate the prognosis associated with resuming warfarin treatment stratified by the type of ICH (hemorrhagic stroke or traumatic ICH). This nationwide observational cohort study included patients with AF who sustained an incident ICH event during warfarin treatment from January 1, 1998, through February 28, 2016. Follow-up was completed April 30, 2016. Resumption of warfarin treatment was evaluated after hospital discharge. No oral anticoagulant treatment or resumption of warfarin treatment, included as a time-dependent exposure. One-year observed event rates per 100 person-years were calculated, and treatment strategies were compared using time-dependent Cox proportional hazards regression models with adjustment for age, sex, length of hospital stay, comorbidities, and concomitant medication use. A total of 2415 patients with AF in this cohort (1481 men [61.3%] and 934 women [38.7%]; mean [SD] age, 77.1 years [9.1 years]) sustained an ICH event. Of these events, 1325 were attributable to hemorrhagic stroke and 1090 were secondary to trauma. During the first year, 305 patients with a hemorrhagic stroke (23.0%) died, whereas 210 in the traumatic ICH group (19.3%) died. Among patients with hemorrhagic stroke, resuming warfarin therapy was associated with a lower rate of ischemic stroke or systemic embolism (SE) (adjusted hazard ratio [AHR], 0.49; 95% CI, 0.24-1.02) and an increased rate of recurrent ICH (AHR, 1.31; 95% CI, 0.68-2.50) compared with not resuming warfarin therapy, but these differences did not reach statistical significance. For patients with traumatic ICH, resuming warfarin therapy also was associated with a lower rate of ischemic stroke

  1. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V

    DEFF Research Database (Denmark)

    White, Harvey D; Gruber, Michael; Feyzi, Jan

    2007-01-01

    ) may be related to INR control. METHODS: We analyzed the relationship between INR control and the rates of death, bleeding, MI, and stroke or SEE among 3587 patients with atrial fibrillation randomized to receive warfarin treatment in the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor......BACKGROUND: Warfarin sodium reduces stroke risk in patients with atrial fibrillation, but international normalized ratio (INR) monitoring is required. Target INRs are frequently not achieved, and the risk of death, bleeding, myocardial infarction (MI), and stroke or systemic embolism event (SEE...... were compared according to INR control. The main outcome measures were death, bleeding, MI, and stroke or SEE. RESULTS: The poor control group had higher rates of annual mortality (4.20%) and major bleeding (3.85%) compared with the moderate control group (1.84% and 1.96%, respectively) and the good...

  2. Effect of age and sex on warfarin dosing

    Directory of Open Access Journals (Sweden)

    Khoury G

    2014-07-01

    Full Text Available Ghada Khoury,1 Marwan Sheikh-Taha2 1School of Pharmacy, 2Department of Pharmacy Practice, Lebanese American University, Byblos, Lebanon Objective: We examined the potential effect of sex and age on warfarin dosing in ambulatory adult patients. Methods: We conducted a retrospective chart review of patients attending an anticoagulation clinic. We included patients anticoagulated with warfarin for atrial fibrillation or venous thromboembolism who had a therapeutic international normalized ratio of 2–3 for 2 consecutive months. We excluded patients who had been on any drug that is known to have a major interaction with warfarin, smokers, and heavy alcohol consumers. Out of 340 screened medical records, 96 met the predetermined inclusion criteria. The primary outcome assessed was warfarin total weekly dose (TWD. Results: There was a statistically significant difference in the TWD among the ages (P<0.01; older patients required lower doses. However there was no statistically significant difference in the TWD between sexes (P=0.281. Conclusion: Age was found to have a significant effect on warfarin dosing. Even though women did require a lower TWD than men, this observation was not statistically significant. Keywords: warfarin, INR, anticoagulation, vitamin K antagonists, age

  3. The potential interaction between oral anticoagulants and acetaminophen in everyday practice

    NARCIS (Netherlands)

    van den Bemt, PMLA; Geven, LM; Kuitert, NA; Risselada, A; Brouwers, JRBJ

    2002-01-01

    Objective: The drug-drug interaction between oral anticoagulants (especially warfarin) and acetaminophen has been described, but evidence is conflicting and evidence for a similar interaction between acenocoumarol or phenprocoumon and acetaminophen is limited. Therefore, a study was performed to

  4. Health Care Resource Utilization, Costs, and Persistence in Patients Newly Diagnosed as Having Nonvalvular Atrial Fibrillation and Newly Treated With Dabigatran versus Warfarin in the United States.

    Science.gov (United States)

    Bancroft, Tim; Lim, Jonathan; Wang, Cheng; Sander, Stephen D; Swindle, Jason P

    2016-03-01

    This study compared health care resource utilization (HCRU), costs, and persistence among patients newly diagnosed as having nonvalvular atrial fibrillation (NVAF) and newly treated with dabigatran versus warfarin. This retrospective claims-based study used data from a large US managed care organization. The earliest claim for dabigatran or warfarin during October 1, 2010 through October 31, 2011 was the index date, with cohort assignment based on index medication. Evidence of newly diagnosed NVAF within 30 days before the index date and no claims for oral anticoagulants during the 12-month preindex period were required. Cohorts were matched using propensity scores. Per-patient-per-month HCRU, costs, and persistence were calculated during the variable follow-up period of up to 12 months after the index date. Descriptive and multivariable analyses were used to examine differences in outcomes. After matching, 869 patients per cohort were identified (mean age, 67.8 years; 40.4% female). Compared with warfarin, dabigatran had fewer per-patient-per-month emergency department (0.10 vs 0.13, P = 0.010), office (1.98 vs 2.96, P < 0.001), and outpatient (1.05 vs 1.48, P < 0.001) visits. Despite higher mean pharmacy costs for dabigatran (P < 0.001), mean total health care (P = 0.309) and medical costs (P = 0.568) were similar to warfarin. Persistence was higher with dabigatran versus warfarin (median, 204 vs 161 days; mean, 213.7 vs 195.5 days, P = 0.001). Among patients newly diagnosed as having NVAF, those newly treated with dabigatran had lower HCRU, higher persistence, and similar total health care costs compared with those treated with warfarin. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. Assessment of Pharmacokinetic Interactions Between Obeticholic Acid and Caffeine, Midazolam, Warfarin, Dextromethorphan, Omeprazole, Rosuvastatin, and Digoxin in Phase 1 Studies in Healthy Subjects.

    Science.gov (United States)

    Edwards, Jeffrey E; Eliot, Lise; Parkinson, Andrew; Karan, Sharon; MacConell, Leigh

    2017-09-01

    Obeticholic acid (OCA), a potent and selective farnesoid X receptor agonist, is indicated for the treatment of primary biliary cholangitis (PBC). We investigated the potential drug-drug interaction effect of OCA on metabolic CYP450 enzymes and drug transporters. Five phase 1 single-center, open-label, fixed-sequence, inpatient studies were conducted in healthy adult subjects to evaluate the effect of oral daily doses of 10 or 25 mg OCA on single-dose plasma pharmacokinetics of specific probe substrates for enzymes CYP1A2 (caffeine, R-warfarin), CYP3A (midazolam, R-warfarin), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphan), CYP2C19 (omeprazole), and drug transporters, BCRP/OATP1B1/OATP1B3 (rosuvastatin), and P-gp (digoxin). OCA showed no substantial suppression/inhibition of S-warfarin, digoxin, and dextromethorphan and weak interactions with caffeine, omeprazole, rosuvastatin, and midazolam. The maximal pharmacodynamic responses (E max ) to warfarin-based INR, PT, and aPTT were reduced by 11%, 11%, and 1%, respectively, for the 10-mg dose group and by 7%, 7% and 0%, respectively, for the 25-mg dose group. Overall, drugs dosed in combination with OCA were well tolerated, and most adverse events were mild in severity. No clinically important trends were noted in laboratory evaluations, vital signs, or 12-lead ECGs. In these studies, OCA showed weak to no suppression/inhibition of metabolic enzymes and drug transporters at the highest recommended therapeutic dose in patients with PBC. On the basis on these analyses, monitoring and maintenance of target INR range are required during coadministration of OCA with drugs that are metabolized by CYP1A2 (R-warfarin). Intercept Pharmaceuticals, Inc.

  6. Possible warfarin failure due to interaction with smokeless tobacco.

    Science.gov (United States)

    Kuykendall, Jim R; Houle, Michael D; Rhodes, Richard S

    2004-04-01

    To report a case of possible interaction of smokeless tobacco with warfarin in a patient treated after several thromboembolic events. A white man with a long history of smokeless tobacco use was unsuccessfully treated with warfarin up to 25-30 mg/day. International normalized ratio (INR) values never stabilized >2.0 over 4.5 years of therapy. This patient had experienced 3 myocardial infarctions (MIs) and 2 ischemic strokes between the ages of 29 and 31 years and experienced another MI at age 33 years. This was followed by several episodes of transient ischemic attacks at age 34 years. During the final year of warfarin treatment, tobacco use was terminated, followed by an increase in INR values from 1.1 to 2.3 within one week. Warfarin therapy was discontinued and smokeless tobacco use was reinstated and tapered slowly to discontinuation. Following warfarin discontinuation, ticlopidine therapy was initiated. Subsequently, this patient was placed on long-term clopidogrel therapy. Mechanisms responsible for this interaction have not been established, but would most likely involve an increased dietary source of vitamin K from tobacco. Tobacco contains high levels of vitamin K, and its use may have contributed directly to the failure of warfarin therapy to achieve therapeutic INR levels in this patient. An objective causality scale indicates a probable association between this combination and the adverse effects. Smokeless tobacco use should be charted in patients undergoing warfarin therapy, and patients who desire to stop tobacco use should be aided in this process. Possible health effects of smokeless tobacco may include potential drug interactions. These interactions may be based on pharmacodynamic and/or pharmacokinetic parameters involving any of the many pharmacologically active substituents of tobacco. Proposed mechanisms of drug interaction may include increased vitamin K levels in the diet.

  7. Potentiation of fluindione or warfarin by dexamethasone in multiple myeloma and AL amyloidosis.

    Science.gov (United States)

    Sellam, Jérémie; Costedoat-Chalumeau, Nathalie; Amoura, Zahir; Aymard, Guy; Choquet, Sylvain; Trad, Salim; Vignes, Bénédicte Lebrun; Hulot, Jean-Sébastien; Berenbaum, Francis; Lechat, Philippe; Cacoub, Patrice; Ankri, Annick; Mariette, Xavier; Leblond, Véronique; Piette, Jean-Charles

    2007-10-01

    Patients with primary systemic (AL) amyloidosis or multiple myeloma are frequently treated with cyclic dexamethasone (DXM) courses and often require oral anticoagulants. We previously reported a strong potentiation of oral anticoagulants with intravenous methylprednisolone and observed a similar potentiation with DXM in 3 patients, which led us to prospectively investigate the interaction between DXM and oral anticoagulants. Nine patients with multiple myeloma (n=6) or AL amyloidosis (n=3), including 6 prospective patients, taking fluindione (n=8) or warfarin (n=1), were studied for a total of 10 cycles. DXM (40 mg/day for 4 days every 28 days) was administered alone (n=4) or with melphalan (n=5). One patient was studied for 2 consecutive cycles after a moderate increase in the international normalized ratio (INR) during the first course of DXM. International normalized ratio (INR) was measured serially during DXM administration. Plasma oral anticoagulant concentrations were measured for 5 cycles. The mean INR increased from 2.75 (range: 1.80-3.6) at baseline to 5.22 (3.09-7.07) after DXM. Oral anticoagulants were transiently stopped during 8 cycles and 1 mg oral vitamin K was given during 2. No serious bleeding was observed. Plasma oral anticoagulant concentrations increased after DXM administration. In controls receiving DXM without oral anticoagulants, DXM alone did not increase prothrombin time. High dose DXM can potentiate oral anticoagulants and elevate INR substantially. INR should therefore be monitored repeatedly during concomitant administration of these 2 drugs to allow individual adaptation of oral anticoagulant doses.

  8. Risk of gastrointestinal adverse effects of dabigatran compared with warfarin among patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Staerk, Laila; Gislason, Gunnar H; Lip, Gregory Y H

    2015-01-01

    , gastritis, gastric, and duodenal ulcer) and gastrointestinal bleeding requiring hospitalization, gastroscopy, and discontinuation of dabigatran and warfarin was examined by cumulative incidence rates and multivariable adjusted Cox regression models. We identified five groups: OAC-naive warfarin (n = 4534...

  9. Management of major bleeding events in patients treated with rivaroxaban vs. warfarin: results from the ROCKET AF trial.

    Science.gov (United States)

    Piccini, Jonathan P; Garg, Jyotsna; Patel, Manesh R; Lokhnygina, Yuliya; Goodman, Shaun G; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Nessel, Christopher C; Mahaffey, Kenneth W; Singer, Daniel E; Califf, Robert M; Fox, Keith A A

    2014-07-21

    There are no data regarding management and outcomes of major bleeding events in patients treated with oral factor Xa inhibitors. Using data from ROCKET AF, we analysed the management and outcomes of major bleeding overall and according to the randomized treatment. During a median follow-up of 1.9 years, 779 (5.5%) patients experienced major bleeding at a rate of 3.52 events/100 patient-years with a similar event rate in each arm (n = 395 rivaroxaban vs. n = 384 warfarin). The median number of transfused packed red blood cells (PRBC) per episode was similar in both arms [2 (25th, 75th: 2, 4) units]. Overall, few transfusions of whole blood (n = 14), platelets (n = 10), or cryoprecipitate (n = 2) were used. Transfusion of fresh frozen plasma (FFP) was significantly less in the rivaroxaban arm (n = 45 vs. n = 81 units) after adjustment for covariates [odds ratio (OR) 0.43 (95% CI 0.29-0.66); P ROCKET AF, the use of FFP and PCC was less among those allocated rivaroxaban compared with warfarin. However, use of PRBCs and outcomes after bleeding were similar among patients randomized to rivaroxaban or to warfarin. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.

  10. The effect of broad-spectrum antibiotics on warfarin excretion and metabolism in the rat

    International Nuclear Information System (INIS)

    Remmel, R.P.; Elmer, G.W.

    1981-01-01

    The excretion and metabolism of 14 C-warfarin in rats was examined in a crossover experiment, the first phase consisting of treatment with normal saline, the second phase using the same animals given neomycin, bacitracin, and tetracycline orally. Urine and feces were collected every 24 hours for 72 hours and examined for warfarin and its metabolites, both unconjugated and conjugated. Significantly more radioactivity was eliminated in th feces of antibiotic-treated rats. The feces of antibiotic-treated rats contained only trace amounts of beta-glucuronidase activity. Urine contained a similar ratio of unconjugated to conjugated radioactivity in both treatment groups, but the antibiotic-treated animals had significantly larger amount of conjugates in their feces. Examination of metabolic profiles of conjugated and unconjugated fractions revealed significantly fewer hydroxylated metabolites in antibiotic-treated rats, especially in the feces. The lower amount of hydroxylative metabolism in attributed to a reduction in gut flora-medicated interohepatic recycling caused by the antibiotics

  11. Warfarin resumption following anticoagulant-associated intracranial hemorrhage: A systematic review and meta-analysis.

    Science.gov (United States)

    Chai-Adisaksopha, Chatree; Iorio, Alfonso; Hillis, Christopher; Siegal, Deborah; Witt, Daniel M; Schulman, Sam; Crowther, Mark

    2017-12-01

    This study aims to assess the effect of warfarin resumption in patients who experienced warfarin-associated intracranial hemorrhage (ICH). We conducted a systematic review and meta-analysis of studies evaluating the outcomes of adult patients who survived warfarin-associated ICH. We included studies that compared patients who resumed warfarin versus those who did not. Of 3145 studies screened, ten observational studies were included in the final analysis. Death occurred in 181 of 968 patients (18.7%) who resumed warfarin and 834 of 2579 (32.3%) who did not resume warfarin (RR 0.51, 95% CI 0.34 to 0.76, P=0.0009). Ischemic stroke occurred in 32 of 902 (3.5%) patients who resumed warfarin and 172 of 2467 (7.0%) patients who did not resume warfarin (RR 0.56, 95% CI 0.39 to 0.82, P=0.002). Venous thromboembolism occurred in 4 of 224 (1.8%) patients who resumed warfarin and of 33 of 681 (4.8%) patients who did not resume warfarin (RR 0.39, 95% CI, 0.15 to 1.03, P=0.06). Recurrent ICH occurred in 200 of 2994 (6.7%) patients who resumed warfarin and 358 of 4652 (7.7%) patients who did not resume warfarin (RR 0.89, 95% CI 0.65 to 1.23, P=0.49). The study suggests that warfarin resumption is associated with significant reduction in ischemic stroke and venous thromboembolism when compared to no warfarin resumption in patients who experience warfarin-associated ICH. Although these results are strongly supportive of restarting anticoagulation, prospective studies are required to confirm our results due to the high likelihood of bias in the included studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Race influences warfarin dose changes associated with genetic factors.

    Science.gov (United States)

    Limdi, Nita A; Brown, Todd M; Yan, Qi; Thigpen, Jonathan L; Shendre, Aditi; Liu, Nianjun; Hill, Charles E; Arnett, Donna K; Beasley, T Mark

    2015-07-23

    Warfarin dosing algorithms adjust for race, assigning a fixed effect size to each predictor, thereby attenuating the differential effect by race. Attenuation likely occurs in both race groups but may be more pronounced in the less-represented race group. Therefore, we evaluated whether the effect of clinical (age, body surface area [BSA], chronic kidney disease [CKD], and amiodarone use) and genetic factors (CYP2C9*2, *3, *5, *6, *11, rs12777823, VKORC1, and CYP4F2) on warfarin dose differs by race using regression analyses among 1357 patients enrolled in a prospective cohort study and compared predictive ability of race-combined vs race-stratified models. Differential effect of predictors by race was assessed using predictor-race interactions in race-combined analyses. Warfarin dose was influenced by age, BSA, CKD, amiodarone use, and CYP2C9*3 and VKORC1 variants in both races, by CYP2C9*2 and CYP4F2 variants in European Americans, and by rs12777823 in African Americans. CYP2C9*2 was associated with a lower dose only among European Americans (20.6% vs 3.0%, P races, the proportional decrease was higher among European Americans (28.9% vs 19.9%, P = .003) compared with African Americans. Race-stratified analysis improved dose prediction in both race groups compared with race-combined analysis. We demonstrate that the effect of predictors on warfarin dose differs by race, which may explain divergent findings reported by recent warfarin pharmacogenetic trials. We recommend that warfarin dosing algorithms should be stratified by race rather than adjusted for race. © 2015 by The American Society of Hematology.

  13. Inhibition of warfarin anticoagulation associated with chelation therapy.

    Science.gov (United States)

    Grebe, Heidi Braun; Gregory, Philip J

    2002-08-01

    Chelation therapy originally was administered exclusively to patients with heavy metal poisoning. Now some physicians are administering this therapy for numerous conditions, most commonly coronary heart disease. A 64-year-old man experienced impaired warfarin anticoagulation after undergoing chelation therapy His international normalized ratio (INR) fell from 2.6 the day before to 1.6 the day after therapy was administered. Whether chelation therapy decreases the effectiveness of warfarin anticoagulation is uncertain. However, because of this potential interaction, clinicians should consider increased INR monitoring in patients undergoing chelation therapy.

  14. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.

    Science.gov (United States)

    Cohen, H; Doré, C J; Clawson, S; Hunt, B J; Isenberg, D; Khamashta, M; Muirhead, N

    2015-09-01

    The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5. © The Author(s) 2015.

  15. Efficacy and safety of apixaban compared with warfarin for stroke prevention in patients with atrial fibrillation from East Asia: a subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial.

    Science.gov (United States)

    Goto, Shinya; Zhu, Jun; Liu, Lisheng; Oh, Byung-Hee; Wojdyla, Daniel M; Aylward, Philip; Bahit, M Cecilia; Gersh, Bernard J; Hanna, Michael; Horowitz, John; Lopes, Renato D; Wallentin, Lars; Xavier, Denis; Alexander, John H

    2014-09-01

    The perceived risk of serious bleeding is an obstacle to the use of oral anticoagulation in East Asia. The efficacy and safety of apixaban in East Asian patients with atrial fibrillation are unknown. ARISTOTLE included 18,201 patients with nonvalvular atrial fibrillation randomized to apixaban 5mg twice daily or warfarin. The efficacy and safety of apixaban and warfarin among patients recruited from East Asia (n = 1,993) were compared with those recruited from outside East Asia (n = 16,208). Compared with warfarin, apixaban resulted in a consistent reduction in stroke or systemic embolism in East Asian (hazard ratio [HR] 0.74, 95% CI 0.50-1.10) and non-East Asian (HR 0.81, 95% CI 0.66-0.99) patients (interaction P = .70). Consistent benefits of apixaban over warfarin were also seen for major bleeding in East Asian (HR 0.53, 95% CI 0.35-0.80) and non-East Asian (HR 0.72, 95% CI 0.62-0.83) patients (interaction P = .17). There was a greater reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin in East Asian (HR 0.49, 95% CI 0.35-0.67) than in non-East Asian (HR 0.71, 95% CI 0.63-0.79) patients (interaction P = .03). Numerically higher rates of intracranial bleeding were seen in East Asian patients with warfarin but not with apixaban. Apixaban resulted in similar reductions in stroke or systemic embolism and major bleeding and greater reductions in major or clinically relevant nonmajor bleeding in patients from East Asia. Warfarin is associated with more intracranial bleeding, particularly in patients from East Asia. Copyright © 2014 Mosby, Inc. All rights reserved.

  16. Natural history of bleeding and characteristics of early bleeders among warfarin initiators – a cohort study in Finland

    Directory of Open Access Journals (Sweden)

    Rikala M

    2016-02-01

    Full Text Available Maria Rikala,1 Helena Kastarinen,1,2 Pekka Tiittanen,1 Risto Huupponen,1,3 Maarit Jaana Korhonen1,4,5 1Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, 2Social Insurance Institution, Regional Office for Eastern and Northern Finland, Kuopio, 3Unit of Clinical Pharmacology, Turku University Hospital, 4Department of Public Health, University of Turku, Turku, Finland; 5Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, NC, USA Aims: The demand for oral anticoagulant therapy will continue to increase in the future along with the aging of the population. This study aimed to determine the rate of bleeding requiring hospitalization and to characterize early bleeders among persons initiating warfarin therapy. Characterization of those most susceptible to early bleeding is important in order to increase the safety of warfarin initiation. Patients and methods: Using data from nationwide health registers, we identified persons initiating warfarin therapy between January 1, 2009 and June 30, 2012, n=101,588, and followed them until hospitalization for bleeding, death, or administrative end of the study (December 31, 2012. We defined early bleeders as persons with a bleeding requiring hospitalization within 30 days since warfarin initiation. Results: The rate of hospitalization for bleeding during a median follow-up of 1.9 years was 2.6% per person-year (95% confidence interval [CI] 2.5%–2.7%, with a peak within the first 30 days of warfarin initiation (6.5% per person-year, 95% CI 6.0%–7.1%. In a multivariable Cox proportional hazards regression analysis, early bleeders were characterized by prior bleeding (<180 days before initiation, hazard ratio [HR] =13.7, 95% CI 10.9–17.1; during 180 days–7 years before initiation, HR =1.48, 95% CI 1.15–1.90, male sex (HR =1.32, 95% CI 1.10–1.57, older age (HR =1.13, 95% CI 1.04–1

  17. Evaluation of warfarin management with international normalized ratio self-testing and online remote monitoring and management plus low-dose vitamin k with genomic considerations: a pilot study.

    Science.gov (United States)

    Bussey, Henry I; Bussey, Marie; Bussey-Smith, Kristin L; Frei, Christopher R

    2013-11-01

    As better international normalized ratio (INR) control and self-testing reduce events in warfarin-treated patients, and vitamin K supplementation may improve INR control, our primary objective was to evaluate the effect of a system combining frequent INR self-testing with online remote monitoring and management (STORM₂) and low-dose vitamin K supplementation on INR control; our secondary objectives were to assess the impact of STORM₂ on clinician time and to evaluate the influence of pharmacogenomics on INR stability and warfarin dose after vitamin K supplementation. Prospective pre- and postintervention study. Freestanding clinical research center. Fifty-five patients treated with long-term warfarin therapy who were referred from four anticoagulation clinics and seven medical practices. All patients performed weekly INR self-testing and received vitamin K 100 µg/day and online anticoagulation management for 1 year. INR control and time required for anticoagulation management were assessed, and an analysis of warfarin dosing and INR stability by genetic polymorphism subgroup (vitamin K epoxide reductase complex 1 [VKORC1] and cytochrome P450 2C9 isoenzyme) was performed; vitamin K product content was also analyzed. The percentage of time that the INR is within the time in therapeutic range (TTR) improved from 56% before the intervention to 81% after the intervention (pmanaged warfarin and with the new oral anticoagulants. © 2013 Pharmacotherapy Publications, Inc.

  18. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism

    NARCIS (Netherlands)

    Schulman, Sam; Kearon, Clive; Kakkar, Ajay K.; Schellong, Sebastian; Eriksson, Henry; Baanstra, David; Kvamme, Anne Mathilde; Friedman, Jeffrey; Mismetti, Patrick; Goldhaber, Samuel Z.; Schulman, S.; Eriksson, H.; Goldhaber, S.; Kakkar, A.; Kearon, C.; Mismetti, P.; Schellong, S.; Minar, E.; Bergqvist, D.; Tijssen, J.; Prins, M. [=Martin H.; Büller, H.; Otten, J.; Mac Gillavry, M.; Brandjes, D.; Otten, H.; Peters, R.; Pol, S.; Burroughs, A.; Gilmore, I.; Bluguermann, J.; Bustos, B.; Carlevaro, O.; Cartasegna, L.; Cuello, J.; Gabito, A.; Gitelman, P.; Gutierrez Carrillo, N.; Hrabar, A.; Mackinon, I.; Santos, D.; Schygiel, P.; Sosa Liprandi, M.; Baker, R.; Blombery, P.; Gallus, A.; Gan, E.; McCann, A.; Salem, H.; Koppensteiner, R.; Kyrle, P.; Pilger, E.; Sturm, W.; Hainaut, P.; Verhamme, P.; Wautrecht, J.-C.; Zicot, M.; Bizzachi, J. Annichino; Joyce, M.; Araújo, G.; de Araújo Filho, J. Dalmo; Panico, M. Duarte Brandão; Pereira, A.; Rocha Moreira, R.; Timi, J.; Yamashita, E.; Anastasov, V.; Georgiev, G.; Guirov, K.; Lozev, I.; Milanov, S.; Peneva, M.; Petrov, V.; Yordanov, Y.; Anderson, D.; Crowther, M.; Dolan, S.; Eikelboom, J.; Game, M.; Kahn, S.; Kassis, J.; Klinke, P.; Ritchie, B.; Rodger, M.; Solymoss, S.; Spencer, F.; Yeo, E.; Bai, C.; Liu, C.; Liu, J.; Shen, H.; Wan, H.; Wang, C.; Wang, Y.; Wen, F.; Ying, K.; Yuan, Y.; Zhang, J.; Zhang, L.; Zheng, Q.; Zhong, N.; Bercikova, J.; Cervinka, P.; Cizek, V.; Jirka, V.; Lang, P.; Maly, R.; Oral, I.; Prochazka, P.; Spinar, J.; Brønnum-Schou, J.; Friis, E.; Jensen, S.; Nielsen, H.; Skødebjerg Kristensen, K.; Wiemann, O.; Husted, S.; Kuusisto, A.; Lassila, R.; Melin, J.; Nikkilä, M.; Nousiainen, T.; Bost, V.; Buchmuller, A.; Guillot, K.; Lecomte, F.; Mottier, D.; Wahl, D.; Beyer-Westendorf, J.; Dormann, A.; Harenberg, J.; Hoffmann, U.; Maier, M.; Mietaschk, A.; Salbach, P.; Cohen, A.; Keeling, D.; Kesteven, P.; Maclean, M. R.; Shah, P.; Katsenis, K.; Klonaris, C.; Liappis, C.; Mihailidis, D.; Acsady, G.; Boda, Z.; Farkas, K.; Jakucs, J.; Kollar, L.; Matyas, L.; Muranyi, A.; Riba, M.; Sereg, M.; Banker, D.; Durairaj, N.; Gadkari, M.; Grant, P.; Hiremath, J.; Kareem, S.; Mahajan, R.; Naik, A.; Parakh, R.; Rai, K.; Santhosh, M.; Sekar, N.; Srinivas, A.; Suresh, K.; Vijayaraghavan, G.; Brenner, B.; Efrati, S.; Mazen, E.; Gavish, D.; Grossman, E.; Lahav, M.; Lishner, M.; Lugassy, G.; Zeltser, D.; Barillari, G.; D' Angelo, A.; Palareti, G.; Santonasto, M.; Schenone, A.; Silingardi, M.; Testa, S.; Aldrett Lee, E.; Fontes Andrade, J.; Jaurrieta Valles, J.; Montaño-González, E.; Sánchez-Escalante, L.-R.; Dees, A.; Hamulyak, K.; Jie, A.; Kamphuisen, P.; Leebeek, F.; Nurmohamed, M.; Pruijt, J.; Wittebol, S.; Hanna, M.; Jackson, S.; Ockelford, P.; Smith, M.; Njaastad, A.; Sandseth, P.; Tveit, A.; Waage, A.; Czarnobilski, K.; Gaciong, Z.; Gluszek, S.; Krolczyk, J.; Zawilska, K.; Barata, J.; Capitao, M.; e Fernandes, F.; Martinez, J.; Providência, L.; Sarmento, P.; Belentsov, S.; Chernyatina, M.; Chernyavsky, A.; Degterev, M.; Fokin, A.; Gubenko, A.; Guz, V.; Katelnitsky, I.; Khamitov, A.; Khitaryan, A.; Khubulava, G.; Koulikovsky, V.; Nelaev, V.; Shkurin, V.; Smirnov, G.; Sokurenko, G.; Soroka, V.; Staroverov, I.; Zaporozhsky, S.; Duris, T.; Poliacik, P.; Spisak, V.; Szentivanyi, M.; Zubek, V.; Adler, D.; Le Roux, D.; Routier, R.; Siebert, R.; Sloane, B.; Smith, C.; del Toro, J.; García-Fuster, M.; Marco, P.; Mateo, J.; Monreal, M.; Nieto J, J.; Sedano, C.; Trujillo, J.; Villalta, J.; Aagesen, J.; Carlsson, A.; Lärfars, G.; Lindmarker, P.; Säfwenberg, U.; Själander, A.; Aslim, E.; Bengisun, U.; Calkavur, T.; Eren, E.; Karahan, S.; Karatepe, O.; Kurtoglu, M.; Sakinci, U.; Gubka, O.; Karpovych, D.; Mishalov, V.; Skupyy, O.; Bartkowiak, A.; Bolster, E.; Burnett, B.; Comerota, A.; Fulco, F.; Gleeson, J.; Gossage, J.; Kaatz, S.; Kuehl, S.; Lahiri, B.; Masson, J.; Moll, S.; Nathanson, A.; Paulson, R.; Powell, R.; Seibert, A.; Vrooman, P.; Sandgren, G.; Wallin, J.; Kälebo, P.; Angerås, U.; Falk, A.; Eriksson, B.; Dellborg, M.; Eriksson, P.; Johansson, P.; Hansson, P. O.; Nicol, A.; Jeffries, B.; Benson, M.; Kyrle, P. A.; Hirschl, M.; Böhler, K.; de Vleeschauwer, P.; Haerens, M.; Duchateau, J.; Verstraeten, P.; Milot, A.; Kotik, L.; Roztocil, K.; Joerg, I.; Holy, M.; Cernosek, B.; Kasalova, Z.; Mandakova, E.; Povolny, J.; Matoska, P.; Hulinsky, V.; Podoubsky, R.; Votocek, S.; Zarubova, D.; Ellervee, T.; Lind, J.; Sukles, K.; Uebel, P.; Bauersachs, R.; Kemkes-Matthes, B.; Beyer, J.; Siragusa, S.; Bova, C.; Cortellaro, M.; Falanga, A.; Palla, A.; Pini, M.; Poggio, R.; Porro, F.; Prisco, D.; Tiraferri, E.; Villalta, S.; Visona, A.; Zanatta, N.; Mazzucconi, M. G.; Porreca, E.; Cattaneo, M.; Di Minno, G.; Oh, D.; Kim, C. S.; Kwon, T. W.; Lee, T. S.; Park, J. S.; Hong, Y. S.; Yoon, S. S.; Kim, Y. K.; Laucevicius, A.; Miliauskas, S.; Novikovs, N.; Zvirgzdins, V.; Meijer, K.; Nijziel, M. R.; van Guldener, C.; van Essen, G. G.; Ouwehand, M. E.; Jie, K. S. G.; Swart-Heikens, J.; Viergever, P. P.; Dullemond, A. C.; Tomkowski, W.; Torbicki, A.; Psuja, P.; Staszkiewicz, W.; Szopinski, P.; Pruszczyk, P.; Ciostek, P.; Windyga, J.; Stepien, J.; Khamitov, A. A.; Ng, H. J.; Elf, J.; Engquist, L.; Sharo, S.; Holmström, M.; Lapidus, L.; Cederin, B.; Brack, T.; Binkert, M.; Canova, C.; Franzeck, U.; Allmann, J. K.; Zehnder, T.; Jeanneret, C.; Jäger, K.; Erni, D.; Banyai, M.; Rödel, C.; Engelbrecht, J.; Bruning, A.; van Rensburg, H.; Vermooten, I. H.; Norasetthada, L.; Thungthong, P.; Angchaisuksiri, P.; Numbenjapon, T.; Cook, R.; Deck, K.; Evans, B.; Hearne, S.; Kaelin, T.; Kuno, R.; Pendelton, R.; Speer, J.; Yood, R.; Kahn, R.; Sheehan, K.; Feldman, G.; Chen, Y. C. J.; Fanning, J.; Hartley, P.; Kulback, S.; McIvor, M. E.; LaPerna, L.; Gibson, K.; Vaid, B. R.; Changlani, M.

    2013-01-01

    Dabigatran, which is administered in a fixed dose and does not require laboratory monitoring, may be suitable for extended treatment of venous thromboembolism. In two double-blind, randomized trials, we compared dabigatran at a dose of 150 mg twice daily with warfarin (active-control study) or with

  19. Multiple doses of trandolapril do not affect warfarin pharmacodynamics

    African Journals Online (AJOL)

    also made by Stirling et al. in 1982.' For this reason a priming dose of 25 mg warfarin alone was given to all volunteers on day 1 of the study. Trandolapril or placebo was given on a randomised basis daily on days 8 through 20 and 22 through 34. The dose of trandolapril was 2 mg and it was given under supervision.

  20. Challenges in management of Warfarin anti-coagulation in ...

    African Journals Online (AJOL)

    Challenges in management of Warfarin anti-coagulation in advanced HIV/AIDS patients with venous thrombotic events - A case series from a research clinic in rural Kericho, Kenya. ... VTE was diagnosed 52 (1-469) days after ART initiation, and 81.8% of cases were outpatients at presentation. All patients received at least ...

  1. Atrial fibrillation and stroke in the perspective of new oral anticoagulants

    OpenAIRE

    Demet Funda Baş; Mehmet Akif Topçuoğlu; Ethem Murat Arsava

    2013-01-01

    Atrial fibrillation is an independent, powerful risk factor for stroke. Until recently, acetyl salicylic acid (aspirin) and warfarin were the only approved treatment options for stroke prophylaxis. Although warfarin provides a significantly better risk reduction in stroke compared to placebo and aspirin, its usage difficulties entailed investigation of new treatment alternatives. Studies showed that new oral anticoagulants (such as dabigatran, apixaban and rivaroxaban) are as efficie...

  2. COST-EFFECTIVENESS OF APIXABAN AS COMPARED WITH WARFARIN AND ACETYLSALICYLIC ACID IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2015-09-01

    Full Text Available Background. For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (such as warfarin, antiplatelet therapy (such as acetylsalicylic acid and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Administration of vitamin K antagonists (VKA is complicated by the need for individual dose adjustment and frequent monitoring of international normalized ratio (INR. Both warfarin and acetylsalicylic acid are widely used for thrombosis prevention in patients with NVAF in the Russian Federation.Aim. To evaluate the cost-effectiveness ratio of apixaban compared with warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective.Material and methods. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER for apixaban as compared with warfarin and acetylsalicylic acid over lifetime horizon in VKA suitable and VKA unsuitable patients with NVAF respectively. The model enclosed cardiovascular event rates based on the results of the randomized clinical trials comparing clinical effectiveness and safety of apixaban with warfarin (ARISTOTLE and acetylsalicylic acid (AVERROES. The following cardiovascular events were taken into consideration: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the antithrombotic drugs was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality

  3. COST-EFFECTIVENESS OF APIXABAN AS COMPARED WITH WARFARIN AND ACETYLSALICYLIC ACID IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION IN THE RUSSIAN FEDERATION

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2014-01-01

    Full Text Available Background. For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (such as warfarin, antiplatelet therapy (such as acetylsalicylic acid and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Administration of vitamin K antagonists (VKA is complicated by the need for individual dose adjustment and frequent monitoring of international normalized ratio (INR. Both warfarin and acetylsalicylic acid are widely used for thrombosis prevention in patients with NVAF in the Russian Federation.Aim. To evaluate the cost-effectiveness ratio of apixaban compared with warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective.Material and methods. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER for apixaban as compared with warfarin and acetylsalicylic acid over lifetime horizon in VKA suitable and VKA unsuitable patients with NVAF respectively. The model enclosed cardiovascular event rates based on the results of the randomized clinical trials comparing clinical effectiveness and safety of apixaban with warfarin (ARISTOTLE and acetylsalicylic acid (AVERROES. The following cardiovascular events were taken into consideration: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the antithrombotic drugs was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality

  4. Warfarin skin necrosis mimicking calciphylaxis in a patient with secondary hyperparathyroidism undergoing peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Jee Eun Park

    2016-03-01

    Full Text Available Warfarin skin necrosis (WSN is an infrequent complication of warfarin treatment and is characterized by painful ulcerative skin lesions that appear a few days after the start of warfarin treatment. Calciphylaxis also appears as painful skin lesions caused by tissue injury resulting from localized ischemia caused by calcification of small- to medium-sized vessels in patients with end-stage renal disease. We report on a patient who presented with painful skin ulcers on the lower extremities after the administration of warfarin after a valve operation. Calciphylaxis was considered first because of the host factors; eventually, the skin lesions were diagnosed as WSN by biopsy. The skin lesions improved after warfarin discontinuation and short-term steroid therapy. Most patients with end-stage renal disease have some form of cardiovascular disease and some require temporary or continual warfarin treatment. It is important to differentiate between WSN and calciphylaxis in patients with painful skin lesions.

  5. SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

    Directory of Open Access Journals (Sweden)

    E. L. Artanova

    2011-01-01

    Full Text Available Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, amiodarone therapy were considered among clinical characteristics. Results. Adjusted warfarin dose was significantly higher in obesity , and it was lower in case of experienced myocardial infarction. The INR highest levels and maximal amplitudes of its fluctuations were observed in patients with thyroid gland nodes and smokers. Period of warfarin dose titration was longer in patients treated with amiodarone. Conclusion. Warfarin dose titration in patients with atrial fibrillation depends on the presence of myocardial infarction, obesity , thyroid nodular changes, smoking and amiodarone treatment.

  6. Aspirin versus warfarin in atrial fibrillation: decision analysis may help patients' choice.

    LENUS (Irish Health Repository)

    Romero-Ortuno, Roman

    2012-03-01

    the primary prevention of ischaemic stroke in chronic non-valvular atrial fibrillation (AF) typically involves consideration of aspirin or warfarin. CHA(2)DS(2)-VASc estimates annual stroke rates for untreated AF patients, which are reduced by 60% with warfarin and by 20% with aspirin. HAS-BLED estimates annual rates of major bleeding on warfarin. The latter risk with aspirin is 0.5-1.2% per year.

  7. Fabrication of modified electrochemical sensor using graphen nano particle for determination of warfarin in plasma samples

    OpenAIRE

    Hasanpour F; Taei M; Nekoeinia M; Dadras B; Divanzadeh S

    2017-01-01

    Background and aims: Warfarin is anticoagulant drug and prevents thromboembolism in cases such as pulmonary embolism and blood clot in a leg vein which under high risk of thrombosis. The therapeutic window of warfarin is very narrow. Therefore, it is important to monitoring the level of warfarin in blood patient. Electrochemical sensors are powerful tools in the field of diseases diagnosis and medical care, due to advantages such as high selectivity, high sensitivity and low. The aim of this ...

  8. SPECIAL CONSIDERATIONS REGARDING WARFARIN DOSE TITRATION IN PATIENTS WITH ATRIAL FIBRILLATION DEPENDING ON CLINICAL FACTORS

    OpenAIRE

    E. L. Artanova; E. V. Saleeva; I. M. Sokolov; Y. G. Shvarts

    2011-01-01

    Aim. To study the relations of clinical characteristics and individual warfarin dose titration in patients with atrial fibrillation. Material and methods. Period of warfarin dose titration was analyzed in 68 patients with atrial fibrillation due to ischemic heart disease. Adjusted warfarin dose in milligram, duration of dose titration in days and maximal international normalized ratio (INR) were taken into account. Sex, age, history of myocardial infarction and stroke, concomitant diseases, a...

  9. Comparison of Nine Statistical Model Based Warfarin Pharmacogenetic Dosing Algorithms Using the Racially Diverse International Warfarin Pharmacogenetic Consortium Cohort Database.

    Directory of Open Access Journals (Sweden)

    Rong Liu

    Full Text Available Multiple linear regression (MLR and machine learning techniques in pharmacogenetic algorithm-based warfarin dosing have been reported. However, performances of these algorithms in racially diverse group have never been objectively evaluated and compared. In this literature-based study, we compared the performances of eight machine learning techniques with those of MLR in a large, racially-diverse cohort.MLR, artificial neural network (ANN, regression tree (RT, multivariate adaptive regression splines (MARS, boosted regression tree (BRT, support vector regression (SVR, random forest regression (RFR, lasso regression (LAR and Bayesian additive regression trees (BART were applied in warfarin dose algorithms in a cohort from the International Warfarin Pharmacogenetics Consortium database. Covariates obtained by stepwise regression from 80% of randomly selected patients were used to develop algorithms. To compare the performances of these algorithms, the mean percentage of patients whose predicted dose fell within 20% of the actual dose (mean percentage within 20% and the mean absolute error (MAE were calculated in the remaining 20% of patients. The performances of these techniques in different races, as well as the dose ranges of therapeutic warfarin were compared. Robust results were obtained after 100 rounds of resampling.BART, MARS and SVR were statistically indistinguishable and significantly out performed all the other approaches in the whole cohort (MAE: 8.84-8.96 mg/week, mean percentage within 20%: 45.88%-46.35%. In the White population, MARS and BART showed higher mean percentage within 20% and lower mean MAE than those of MLR (all p values < 0.05. In the Asian population, SVR, BART, MARS and LAR performed the same as MLR. MLR and LAR optimally performed among the Black population. When patients were grouped in terms of warfarin dose range, all machine learning techniques except ANN and LAR showed significantly higher mean percentage within

  10. Warfarin Accelerates Ectopic Mineralization in Abcc6−/− Mice

    Science.gov (United States)

    Li, Qiaoli; Guo, Haitao; Chou, David W.; Harrington, Dominic J.; Schurgers, Leon J.; Terry, Sharon F.; Uitto, Jouni

    2014-01-01

    Pseudoxanthoma elasticum (PXE) is a multisystem ectopic mineralization disorder caused by mutations in the ABCC6 gene. Warfarin, a commonly used anticoagulant, is associated with increased mineralization of the arterial blood vessels and cardiac valves. We hypothesized that warfarin may accelerate ectopic tissue mineralization in PXE, with clinical consequences. To test this hypothesis, we developed a model in which Abcc6−/− mice, which recapitulate features of PXE, were fed a diet supplemented with warfarin and vitamin K1. Warfarin action was confirmed by significantly increased serum levels of oxidized vitamin K. For mice placed on a warfarin-containing diet, quantitative chemical and morphometric analyses revealed massive accumulation of mineral deposits in a number of tissues. Mice fed a warfarin-containing diet were also shown to have abundant uncarboxylated form of matrix Gla protein, which allowed progressive tissue mineralization to ensue. To explore the clinical relevance of these findings, 1747 patients with PXE from the approximately 4000 patients in the PXE International database were surveyed about the use of warfarin. Of the 539 respondents, 2.6% reported past or present use of warfarin. Based on the prevalence of PXE (approximately 1:50,000), thousands of patients with PXE worldwide may be at risk for worsening of PXE as a result of warfarin therapy. PMID:23415960

  11. A systematic analysis and comparison of warfarin initiation strategies

    Science.gov (United States)

    French, Benjamin; Wang, Le; Gage, Brian F.; Horenstein, Richard B.; Limdi, Nita A.; Kimmel, Stephen E.

    2016-01-01

    Objective Randomized trials have reported inconsistent evidence regarding the effectiveness of algorithms that use genotypes to initiate warfarin therapy. The Clarification of Optimal Anticoagulation through Genetics (COAG) trial initiated therapy based on predicted maintenance doses, with a pharmacogenetic-guided algorithm in one study group and a clinically guided algorithm in the other. The European Pharmacogenetics of Anticoagulant Therapy (EU-PACT) consortium initiated therapy based on loading doses, with an algorithm-based prediction in one study group and a fixed-dose regimen in the other. To understand the differences between these trials, we compared the initial doses between alternative dosing algorithms (the pharmacogenetic-guided and clinically guided algorithms developed by Gage and colleagues and those developed by the International Warfarin Pharmacogenetics Consortium), and between the COAG and EU-PACT dose-initiation strategies. Methods Secondary analysis of the COAG trial—a double-blind, randomized controlled trial (2009–2013)—conducted at 18 clinical centers in the United States, which included 1,010 adults initiating warfarin therapy, of whom 719 achieved maintenance dose. Results Among COAG participants, the distribution of initial doses differed between algorithms, but exhibited similar prediction accuracy for maintenance dose. However, had the COAG trial implemented the EU-PACT strategy, the 3-day initial dose would have been 4.8 mg greater among participants randomized to pharmacogenetic-guided dosing, but only 2.5 mg greater among participants randomized to clinically guided dosing (P<0.001). Conclusions Compared to the COAG trial, the EU-PACT trial used systematically larger loading doses in the pharmacogenetic-guided group and might have inadequately adjusted for clinical variability in warfarin dose requirements in the fixed-dose group. PMID:27383664

  12. Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin.

    Science.gov (United States)

    Vinereanu, Dragos; Lopes, Renato D; Mulder, Hillary; Gersh, Bernard J; Hanna, Michael; de Barros E Silva, Pedro G M; Atar, Dan; Wallentin, Lars; Granger, Christopher B; Alexander, John H

    2017-12-01

    Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding. Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography. A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25-3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23-6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71-6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus. In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2017 American Heart Association, Inc.

  13. Percutaneous coronary intervention and antiplatelet therapy in patients with atrial fibrillation receiving apixaban or warfarin: Insights from the ARISTOTLE trial.

    Science.gov (United States)

    Kopin, David; Jones, W Schuyler; Sherwood, Matthew W; Wojdyla, Daniel M; Wallentin, Lars; Lewis, Basil S; Verheugt, Freek W A; Vinereanu, Dragos; Bahit, M Cecilia; Halvorsen, Sigrun; Huber, Kurt; Parkhomenko, Alexander; Granger, Christopher B; Lopes, Renato D; Alexander, John H

    2018-03-01

    We assessed antiplatelet therapy use and outcomes in patients undergoing percutaneous coronary intervention (PCI) during the ARISTOTLE trial. Patients were categorized based on the occurrence of PCI during follow-up (median 1.8 years); PCI details and outcomes post-PCI are reported. Of the 18,201 trial participants, 316 (1.7%) underwent PCI (152 in apixaban group, 164 in warfarin group). At the time of PCI, 84% (267) were on study drug (either apixaban or warfarin). Of these, 19% did not stop study drug during PCI, 49% stopped and restarted 5 days post-PCI. At 30 days post-PCI, 35% of patients received dual -antiplatelet therapy (DAPT), 23% received aspirin only, and 13% received a P2Y 12 inhibitor only; 29% received no antiplatelet therapy. Triple therapy (DAPT + oral anticoagulant [OAC]) was used in 21% of patients, 23% received OAC only, 15% received OAC plus aspirin, and 9% received OAC plus a P2Y 12 inhibitor; 32% received antiplatelet agents without OAC. Post-PCI, patients assigned to apixaban versus warfarin had numerically similar rates of major bleeding (5.93 vs 6.73 events/100 patient-years; P = .95) and stroke (2.74 vs 1.84 events/100 patient-years; P = .62). PCI occurred infrequently during follow-up. Most patients on study drug at the time of PCI remained on study drug in the peri-PCI period; 19% continued the study drug without interruption. Antiplatelet therapy use post-PCI was variable, although most patients received DAPT. Additional data are needed to guide the use of antithrombotics in patients undergoing PCI. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Anticoagulants Resumption after Warfarin-Related Intracerebral Haemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy).

    Science.gov (United States)

    Poli, Loris; Grassi, Mario; Zedde, Marialuisa; Marcheselli, Simona; Silvestrelli, Giorgio; Sessa, Maria; Zini, Andrea; Paciaroni, Maurizio; Azzini, Cristiano; Gamba, Massimo; Toriello, Antonella; Tassi, Rossana; Giorli, Elisa; Calabrò, Rocco Salvatore; Ritelli, Marco; De Vito, Alessandro; Pugliese, Nicola; Martini, Giuseppe; Lanari, Alessia; Lodigiani, Corrado; Padroni, Marina; De Giuli, Valeria; Caria, Filomena; Morotti, Andrea; Costa, Paolo; Strambo, Davide; Corato, Manuel; Pascarella, Rosario; Del Sette, Massimo; Malferrari, Giovanni; Colombi, Marina; Padovani, Alessandro; Pezzini, Alessandro

    2018-03-01

    Whether to resume antithrombotic treatment after oral anticoagulant-related intracerebral haemorrhage (OAC-ICH) is debatable. In this study, we aimed at investigating long-term outcome associated with OAC resumption after warfarin-related ICH, in comparison with secondary prevention strategies with platelet inhibitors or antithrombotic discontinuation. Participants were patients who sustained an incident ICH during warfarin treatment (2002-2014) included in the Multicenter Study on Cerebral Hemorrhage in Italy. Primary end-point was a composite of ischemic stroke/systemic embolism (SE) and all-cause mortality. Secondary end-points were ischemic stroke/SE, all-cause mortality and major recurrent bleeding. We computed individual propensity score (PS) as the probability that a patient resumes OACs or other agents given his pre-treatment variables, and performed Cox multivariable analysis using Inverse Probability of Treatment Weighting (IPTW) procedure. A total of 244 patients qualified for the analysis. Unlike antiplatelet agents, OAC resumption was associated with a lower rate of the primary end-point (weighted hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.09-0.45), as well as of overall mortality (weighted HR, 0.17; 95% CI, 0.06-0.45) and ischemic stroke/SE (weighted HR, 0.19; 95% CI, 0.06-0.60) with no significant increase of major bleeding in comparison with patients receiving no antithrombotics. In the subgroup of patients with atrial fibrillation, OACs resumption was also associated with a reduction of the primary end-point (weighted HR, 0.22; 95% CI, 0.09-0.54), and the secondary end-point ischemic stroke/SE (weighted HR, 0.09; 95% CI, 0.02-0.40). In conclusion, in patients who have an ICH while receiving warfarin, resuming anticoagulation results in a favorable trade-off between bleeding susceptibility and thromboembolic risk. Schattauer GmbH Stuttgart.

  15. Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial.

    Science.gov (United States)

    Singer, Daniel E; Hellkamp, Anne S; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R; Piccini, Jonathan P; Hankey, Graeme J; Breithardt, Günter; Halperin, Jonathan L; Becker, Richard C; Hacke, Werner; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

    2015-03-03

    In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted. TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported. URL: ClinicalTrials.gov. Unique identifier: NCT00403767. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  16. Good quality of oral anticoagulation treatment in general practice using international normalised ratio point of care testing

    DEFF Research Database (Denmark)

    Løkkegaard, Thomas; Pedersen, Tina Heidi; Lind, Bent

    2015-01-01

    collected retrospectively for a period of six months. For each patient, time in therapeutic range (TTR) was calculated and correlated with practice and patient characteristics using multilevel linear regression models. RESULTS: We identified 447 patients in warfarin treatment in the 20 practices using POCT......INTRODUCTION: Oral anticoagulation treatment (OACT) with warfarin is common in general practice. Increasingly, international normalised ratio (INR) point of care testing (POCT) is being used to manage patients. The aim of this study was to describe and analyse the quality of OACT with warfarin...

  17. Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Trial.

    Science.gov (United States)

    Sherwood, Matthew W; Nessel, Christopher C; Hellkamp, Anne S; Mahaffey, Kenneth W; Piccini, Jonathan P; Suh, Eun-Young; Becker, Richard C; Singer, Daniel E; Halperin, Jonathan L; Hankey, Graeme J; Berkowitz, Scott D; Fox, Keith A A; Patel, Manesh R

    2015-12-01

    Gastrointestinal (GI) bleeding is a common complication of oral anticoagulation. This study evaluated GI bleeding in patients who received at least 1 dose of the study drug in the on-treatment arm of the ROCKET AF (Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial. The primary outcome was adjudicated GI bleeding reported from first to last drug dose + 2 days. Multivariable modeling was performed with pre-specified candidate predictors. Of 14,236 patients, 684 experienced GI bleeding during follow-up. These patients were older (median age 75 years vs. 73 years) and less often female. GI bleeding events occurred in the upper GI tract (48%), lower GI tract (23%), and rectum (29%) without differences between treatment arms. There was a significantly higher rate of major or nonmajor clinical GI bleeding in rivaroxaban- versus warfarin-treated patients (3.61 events/100 patient-years vs. 2.60 events/100 patient-years; hazard ratio: 1.42; 95% confidence interval: 1.22 to 1.66). Severe GI bleeding rates were similar between treatment arms (0.47 events/100 patient-years vs. 0.41 events/100 patient-years; p = 0.39; 0.01 events/100 patient-years vs. 0.04 events/100 patient-years; p = 0.15, respectively), and fatal GI bleeding events were rare (0.01 events/100 patient-years vs. 0.04 events/100 patient-years; 1 fatal events vs. 5 fatal events total). Independent clinical factors most strongly associated with GI bleeding were baseline anemia, history of GI bleeding, and long-term aspirin use. In the ROCKET AF trial, rivaroxaban increased GI bleeding compared with warfarin. The absolute fatality rate from GI bleeding was low and similar in both treatment arms. Our results further illustrate the need for minimizing modifiable risk factors for GI bleeding in patients on oral anticoagulation. Copyright © 2015 American College of Cardiology Foundation. Published by

  18. An evaluation of the potential drug interaction between warfarin and levothyroxine.

    Science.gov (United States)

    Wood, M D; Delate, T; Clark, M; Clark, N; Horn, J R; Witt, D M

    2014-08-01

    Drug interaction references report that initiation of levothyroxine potentiates the effects of warfarin, and recommend more frequent International Normalized Ratio (INR) monitoring, but the mechanism is not well understood. To assess the impact of levothyroxine initiation on INR response. A retrospective, self-controlled study was performed on patients aged ≥ 18 years receiving chronic warfarin therapy who were started on levothyroxine between 1 January 2006 and 30 June 2013, and who were followed for 90 days prior to and after levothyroxine initiation. The included patients had at least one elevated thyroid-stimulating hormone laboratory value in the pre-period, continuous warfarin therapy for 100 days prior to levothyroxine initiation, no purchases of medications known to interact with warfarin, no procedures requiring warfarin interruption, and no bleeding or thromboembolic event during the study period. The primary outcome was a comparison of the warfarin dose/INR ratio recorded before the initiation of levothyroxine with the ratio recorded during the post-period after two consecutive INRs with no warfarin dose change. One hundred and two patients were included in the primary outcome. The mean warfarin dose/INR ratios in the pre-period and post-period were equivalent (P = 0.825). Although the mean warfarin dose was numerically lower in the post-period than in the pre-period, this difference did not reach statistical significance (P = 0.068). No difference in the mean warfarin dose/INR ratio before and after initiation of levothyroxine was detected. The results suggest that there is not a clinically significant interaction between warfarin and levothyroxine, and so additional monitoring may not be necessary. © 2014 International Society on Thrombosis and Haemostasis.

  19. Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation.

    Science.gov (United States)

    Cha, Myung-Jin; Choi, Eue-Keun; Han, Kyung-Do; Lee, So-Ryoung; Lim, Woo-Hyun; Oh, Seil; Lip, Gregory Y H

    2017-11-01

    There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients. Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA 2 DS 2 -VASc score ≥2) between 2014 and 2015. NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant-naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH. In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban. © 2017 American Heart Association, Inc.

  20. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial

    NARCIS (Netherlands)

    Alexander, J.H.; Lopes, R.D.; Thomas, L.; Alings, M.; Atar, D.; Aylward, P.; Goto, S.; Hanna, M.; Huber, K.; Husted, S.; Lewis, B.S.; McMurray, J.J.; Pais, P.; Pouleur, H.; Steg, P.G.; Verheugt, F.W.A.; Wojdyla, D.M.; Granger, C.B.; Wallentin, L.

    2014-01-01

    AIMS: We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). METHODS AND RESULTS: In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was

  1. Fatal cerebral blødning på grund af mulig interaktionmellem paracetamol og warfarin

    DEFF Research Database (Denmark)

    Vinsand Naver, Signe; Papina, Maria; Jimenez Solem, Espen

    2015-01-01

    This is a case report of an 83-year-old man in warfarin treatment with stable international normalised ratio (INR) after aortic valve replacement and atrial fibrillation. Due to back pain he took paracetamol (acetaminophen) 4 g/day, morphine 30 mg/day and diclofenac as rescue medication for two...... paracetamol and warfarin are discussed....

  2. Warfarin-induced skin necrosis in HIV-1-infected patients with ...

    African Journals Online (AJOL)

    The median duration of parallel heparin and warfarin therapy was 2 days (range 1 - 6). WISN manifested 6 days (range 4 - 8) after initiation of warfarin therapy. The international normalised ratio (INR) at WISN onset was supra-therapeutic, median 5.6 (range 3.8 - 6.6). Sites of WISN included breasts, buttocks and thighs.

  3. Warfarin for the prevention of systemic embolism in patients with non-valvular atrial fibrillation

    DEFF Research Database (Denmark)

    Andersen, L V; Vestergaard, P; Deichgraeber, P

    2008-01-01

    Warfarin for stroke prevention in patients with atrial fibrillation (AF) is well documented. However, it has not been examined in the prevention of systemic embolism.......Warfarin for stroke prevention in patients with atrial fibrillation (AF) is well documented. However, it has not been examined in the prevention of systemic embolism....

  4. The potential drug-drug interaction between proton pump inhibitors and warfarin

    DEFF Research Database (Denmark)

    Henriksen, Daniel Pilsgaard; Stage, Tore Bjerregaard; Hansen, Morten Rix

    2015-01-01

    BACKGROUND: Proton pump inhibitors (PPIs) have been suggested to increase the effect of warfarin, and clinical guidelines recommend careful monitoring of international normalized ratio (INR) when initiating PPI among warfarin users. However, this drug-drug interaction is sparsely investigated...... before and after PPI initiation. Sensitivity analyses revealed no differences among individual PPIs. CONCLUSIONS: We found no evidence of a clinically meaningful drug-drug interaction between PPIs and warfarin in a Northern European patient population of unselected patients from an everyday outpatient...... and outpatient clinics and their use of prescription drugs. Data were analyzed in 2015. We assessed INR, warfarin dose, and dose/INR ratio before and after initiating PPI treatment using the paired student's t-test. RESULTS: We identified 305 warfarin users initiating treatment with PPIs. The median age was 71...

  5. Effects of aging and rifampicin pretreatment on the pharmacokinetics of human cytochrome P450 probes caffeine, warfarin, omeprazole, metoprolol and midazolam in common marmosets genotyped for cytochrome P450 2C19.

    Science.gov (United States)

    Toda, Akiko; Uehara, Shotaro; Inoue, Takashi; Utoh, Masahiro; Kusama, Takashi; Shimizu, Makiko; Uno, Yasuhiro; Mogi, Masayuki; Sasaki, Erika; Yamazaki, Hiroshi

    2017-07-25

    1. The pharmacokinetics were investigated for human cytochrome P450 probes after single intravenous and oral administrations of 0.20 and 1.0 mg/kg, respectively, of caffeine, warfarin, omeprazole, metoprolol and midazolam to aged (10-14 years old, n = 4) or rifampicin-treated/young (3 years old, n = 3) male common marmosets all genotyped as heterozygous for a cytochrome P450 2C19 variant. 2. Slopes of the plasma concentration-time curves after intravenous administration of warfarin and midazolam were slightly, but significantly (two-way analysis of variance), decreased in aged marmosets compared with young marmosets. The mean hepatic clearances determined by in silico fitting for individual pharmacokinetic models of warfarin and midazolam in the aged group were, respectively, 23% and 56% smaller than those for the young group. 3. Significantly enhanced plasma clearances of caffeine, warfarin, omeprazole and midazolam were evident in young marmosets pretreated with rifampicin (25 mg/kg daily for 4 days). Two- to three-fold increases in hepatic intrinsic clearance values were observed in the individual pharmacokinetic models. 4. The in vivo dispositions of multiple simultaneously administered drugs in old, young and P450-enzyme-induced marmosets were elucidated. The results suggest that common marmosets could be experimental models for aged, induced or polymorphic P450 enzymes in P450-dependent drug metabolism studies.

  6. Review of Warfarin; A Cytochrome P450 Metabolizing Drug, in Clinical Practice

    Directory of Open Access Journals (Sweden)

    Tolou-Ghamari

    2016-04-01

    Full Text Available Context For the prevention and management of thromboembolic complications, warfarin is the most extensively recommended anticoagulant. It is categorized as a drug with a narrow therapeutic window. Therefore, warfarin prescription requires special attention related to therapeutic drug monitoring. Evidence Acquisition By categorizing the clinical implications of warfarin, this manuscript aims to provide a comprehensive (albeit somewhat brief conclusion associated with its pharmacotherapy. The key words relevant to the topic were searched. Consequently, articles relevant to the pharmacotherapeutic management of warfarin were selected and reviewed in their entirety. Results To obtain a reasonable level of stability between the required antithrombotic treatment and the risk of bleeding, an analysis of the literature revealed that the prothrombin time in terms of the international normalized ratio (INR was found for each individual. The best model for stable warfarin dosage prediction was found to be based on multiple linear regression. Genotype-guided procedures were established to: 1, improve the time in the therapeutic range; 2, reduce time to the first therapeutic INR; and 3, reduce the time for the stable doses. Vitamin K epoxide reductase is an enzyme with an important role in vitamin K metabolism, and warfarin is metabolized in hepatocytes via a monooxygenase, cytochrome P450 2C9. In patients carrying 2C9*1/*2 and 2C9*2/*2 or 2C9*1/*3 alleles, the dose is recommended to be reduced by 18% - 40% and 21% - 49%, respectively. Conclusions Race, age, body surface area, chronic kidney disease, CYP2C9*3 level, and VKORC1 variants could affect the dose of warfarin. To administer the proper doses of warfarin, patients and physicians might achieve the best results with the pharmacologist proficient anticoagulation database and recommended continuation program. Owing to its’ unpredictability, caution must be taken when prescribing warfarin. More advanced

  7. Inadvertent exaggerated anticoagulation following use of bismuth subsalicylate in an enterally fed patient receiving warfarin therapy.

    Science.gov (United States)

    Bingham, Angela L; Brown, Rex O; Dickerson, Roland N

    2013-12-01

    We report a case of an inadvertent increase in the international normalized ratio (INR) after the addition of bismuth subsalicylate for the treatment of diarrhea in an enterally fed patient receiving warfarin therapy. A 56-year-old Caucasian female presented to the trauma intensive care unit (ICU) with multiple lower extremity fractures. Warfarin was initiated for deep vein thrombosis prophylaxis due to the patient's inability to ambulate. The target INR was 2-3. Continuous intragastric enteral feeding was withheld 1 hour before and 1 hour after intragastric administration of warfarin. Bismuth subsalicylate 30 mL every 4 hours was prescribed for diarrhea. Within 3 days after starting bismuth subsalicylate therapy, the patient's INR increased from 2.56 to 3.54 and minor bleeding was noted from the patient's tracheostomy site. No significant change in warfarin dosage, variability in vitamin K intake, or medications that potentially alter warfarin metabolism were present during the unexpected rise in INR. When the bismuth subsalicylate was discontinued, the patient's INR stabilized into the target range on the same warfarin dose given at the time of the supratherapeutic INR. Salicylate displaces warfarin from plasma protein binding sites and may result in a significant increase in INR secondary to redistribution of warfarin to the free active form. Evaluation of this case report using the Drug Interaction Probability Scale and Naranjo Adverse Drug Reaction Probability Scale yielded scores consistent with a probable adverse drug interaction. Bismuth subsalicylate exaggerates warfarin's anticoagulant response and its concurrent use during warfarin therapy should be avoided.

  8. Which oral anticoagulant for which atrial fibrillation patient: recent clinical trials and evidence-based choices.

    Science.gov (United States)

    Cairns, John A

    2013-10-01

    Current practice guidelines recommend oral anticoagulant therapy for most patients with nonvalvular atrial fibrillation with more than a low risk of stroke. Although warfarin is very effective and the risk of major bleeding is acceptable, the use of the drug is challenging for patients and physicians. The 3 novel oral anticoagulants (NOACs), dabigatran, rivaroxaban, and apixaban, have been shown to be either noninferior or superior to warfarin for the prevention of stroke and/or systemic embolism and their rates of major bleeding are no greater than warfarin. They are much easier for patients to use and for physicians to manage. Except for certain situations in which the NOACs have not been evaluated or some feature of warfarin is preferable, clinical guidelines generally recommend a preference for a NOAC over warfarin when oral anticoagulation is indicated. Although the NOACs have many similarities in their advantageous pharmacokinetic and pharmacodynamic characteristics, there are a number of difference between them with regard to particular patient characteristics (eg, age ≥ 75 years, renal dysfunction, coronary artery disease, venous thromboembolism, risk of bleeding, prior stroke and/or transient ischemic attack, side effects, dose regimens, and cost-effectiveness). These differences are outlined and discussed in terms of their potential relevance in deciding among the 3 available NOACs for stroke prevention in atrial fibrillation. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  9. Divergent effects of raloxifene HCI on the pharmacokinetics and pharmacodynamics of warfarin.

    Science.gov (United States)

    Miller, J W; Skerjanec, A; Knadler, M P; Ghosh, A; Allerheiligen, S R

    2001-07-01

    Evista (raloxifene HCl) is a nonsteroidal selective estrogen receptor modulator that displays estrogen agonist effects on bone and lipid metabolism but estrogen antagonist effects on the breast and endometrium. The potential for drug-drug interaction between raloxifene and warfarin was assessed in 15 healthy postmenopausal women. Single doses of warfarin (20 mg) were administered prior to and during 2 weeks of dosing with raloxifene 120 mg/day. Each warfarin dose was followed by pharmacokinetic sampling and prothrombin time measurements. Raloxifene administration resulted in 7.1% and 14.1% decreases in the clearance (CLp/F) and 7.4% and 9.8% decreases in the volume of distribution (Vss/F) of R- and S-warfarin, respectively (all p < or = 0.05). In contrast to the slightly higher plasma concentrations of R- and S-warfarin, raloxifene reduced the maximum prothrombin time (PTmax) by 10% and the area under the PT versus time curve from 0-120 h (AUCPT) by 8% (p < 0.01). Raloxifene administration may result in a small increase in systemic warfarin exposure that is associated with a diminution, not augmentation, of the pharmacodynamic effect. Due to the small magnitude of this effect, concomitant administration of raloxifene and warfarin is not likely to result in clinically significant drug-drug interaction.

  10. Use of an iPad to Provide Warfarin Video Education to Hospitalized Patients.

    Science.gov (United States)

    Kim, Jenny Jane; Mohammad, Rima A; Coley, Kim C; Donihi, Amy C

    2015-09-01

    To evaluate the effectiveness of a warfarin educational video in the hospital setting and to determine patients' satisfaction with using an iPad to view a warfarin educational video. This prospective quality improvement project included adult (≥18 years of age) patients on warfarin in the hospital. All patients completed pre-video and post-video knowledge tests on the iPad before and after viewing the educational video on warfarin therapy. Patients also completed a patient satisfaction survey. Forty hospitalized patients were educated using the warfarin video and included for analysis. The majority of patients were new to warfarin therapy (65%). Forty-three percent of patients passed the pre-video knowledge test, and 90% passed the post-video knowledge test (P iPad and found it easy to use. Patients who were younger (iPad more than older patients (P = 0.01) and male subjects (P = 0.02), respectively. Also, younger patients found the iPad easier to use compared with patients who were older (P = 0.01). Educating hospitalized patients about warfarin by using a video on an iPad was effective. Video education on an iPad may be an alternative to traditional education in the hospital setting.

  11. Management dilemmas in patients with mechanical heart valves and warfarin-induced major bleeding.

    Science.gov (United States)

    Panduranga, Prashanth; Al-Mukhaini, Mohammed; Al-Muslahi, Muhanna; Haque, Mohammed A; Shehab, Abdullah

    2012-03-26

    Management of warfarin-induced major bleeding in patients with mechanical heart valves is challenging. There is vast controversy and confusion in the type of treatment required to reverse anticoagulation and stop bleeding as well as the ideal time to restart warfarin therapy safely without recurrence of bleeding and/or thromboembolism. Presently, the treatments available to reverse warfarin-induced bleeding are vitamin K, fresh frozen plasma, prothrombin complex concentrates and recombinant activated factor VIIa. Currently, vitamin K and fresh frozen plasma are the recommended treatments in patients with mechanical heart valves and warfarin-induced major bleeding. The safe use of prothrombin complex concentrates and recombinant activated factor VIIa in patients with mechanical heart valves is controversial and needs well-designed clinical studies. With regard to restarting anticoagulation in patients with warfarin-induced major bleeding and mechanical heart valves, the safe period varies from 7-14 d after the onset of bleeding for patients with intracranial bleed and 48-72 h for patients with extra-cranial bleed. In this review article, we present relevant literature about these controversies and suggest recommendations for management of patients with warfarin-induced bleeding and a mechanical heart valve. Furthermore, there is an urgent need for separate specific guidelines from major associations/ professional societies with regard to mechanical heart valves and warfarin-induced bleeding.

  12. Effectiveness of manual pressure hemostasis following transfemoral coronary angiography in patients on therapeutic warfarin anticoagulation.

    Science.gov (United States)

    El-Jack, Seifeddin S; Ruygrok, Peter N; Webster, Mark W I; Stewart, James T; Bass, Nigel M; Armstrong, Guy P; Ormiston, John A; Pornratanarangsi, Suwatchai

    2006-02-15

    We evaluated the effectiveness of manual pressure hemostasis after transfemoral coronary angiography in patients on therapeutic warfarin anticoagulation (international normalized ratio [INR] 2.0 to 3.0) compared with discontinuing warfarin > or =48 hours before the procedure (INR <2.0). There was a low incidence of small hematomas with either strategy (no significant difference) and no major vascular complications. No prolonged hospital stay due to an access site complication was observed, and no thromboembolic events occurred. In conclusion, transfemoral coronary angiography appears to be safe in patients on warfarin with an INR of 2.0 to 3.0).

  13. Patterns of warfarin use and subsequent outcomes in atrial fibrillation in primary care practices

    Directory of Open Access Journals (Sweden)

    Ewen E

    2012-10-01

    Full Text Available Edward Ewen,1 Zugui Zhang,1 Teresa A Simon,2 Paul Kolm,1 Xianchen Liu,3,4 William S Weintraub11Christiana Care Health System, Newark, DE, USA; 2Bristol-Myers Squibb, Princeton, NJ, USA; 3Indiana University School of Medicine, Indianapolis, IN, USA; 4Pfizer, Groton, CT, USABackground: Warfarin is recommended for stroke prevention in high-risk patients with atrial fibrillation. However, it is often underutilized and inadequately managed in actual clinical practice.Objectives: To examine the patterns of warfarin use and their relationship with stroke and bleeding in atrial fibrillation patients in community-based primary care practices.Design: Retrospective longitudinal cohort study.Participants: A total of 1141 atrial fibrillation patients were selected from 17 primary care practices with a shared electronic medical record and characterized by stroke risk, potential barriers to anticoagulation, and comorbid conditions.Main measures: Duration and number of warfarin exposures, interruptions in warfarin exposure > 45 days, stroke, and bleeding events.Results: Among 1141 patients with a mean age of 70 years (standard deviation 13.3 and mean follow-up of 3.4 years (standard deviation 3.0, 764 (67% were treated with warfarin. Warfarin was discontinued within 1 year in 194 (25.4%, and 349 (45.7% remained on warfarin at the end of follow-up. Interruptions in warfarin use were common, occurring in 32.6% (249 of 764 of patients. Those with two or more interruptions were younger and at lower baseline stroke risk when compared to those with no interruptions. There were 76 first strokes and 73 first-bleeding events in the follow-up period. When adjusted for baseline stroke risk, time to warfarin start, and total exposure time, two or more interruptions in warfarin use was associated with an increased risk of stroke (relative risk, 2.29; 95% confidence interval: 1.29–4.07. There was no significant association between warfarin interruptions and bleeding events

  14. Important Information to Know When You Are Taking: Warfarin (Coumadin) and Vitamin K

    Science.gov (United States)

    ... butchers broom, cat’s claw, dong quai, feverfew, forskolin, garlic, ginger, ginkgo, horse chestnut, insositol hexaphosphate, licorice, melilot ( ... taking Vitamin E supplements while taking warfarin (Coumadin). Antibiotics Some antibiotics can either lower vitamin K levels ...

  15. Solitary pulmonary nodule by pulmonary hematoma under warfarin therapy

    International Nuclear Information System (INIS)

    Scheppach, W.; Kulke, H.; Liebau, G.; Braun, H.; Wuerzburg Univ.

    1983-01-01

    Pulmonary hematoma is a rare cause of a pulmonary nodule. Mostly it results from penetrating or blunt chest injuries. The case of a patient is reported, whose chest X-ray showed a pulmonary nodule suspected of malignancy. This patient was maintained permanently on anticoagulants (warfarin derivates) after cardiac valve replacement with a prosthesis. A definite diagnosis could not be established by non-invasive methods. A needle biopsy of the lung was impracticable because of the location of the pulmonary lesion; an exploratory thoracotomy could not be carried out due to a general indication of nonoperability. Control examinations showed that the pulmonary nodule had vanished completely within four months. In consideration of the patient's clinical situation it can be concluded that the pulmonary lesion was caused by a hematoma of the lung. (orig.) [de

  16. Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation: insights from the ARISTOTLE trial.

    Science.gov (United States)

    Alexander, John H; Lopes, Renato D; Thomas, Laine; Alings, Marco; Atar, Dan; Aylward, Philip; Goto, Shinya; Hanna, Michael; Huber, Kurt; Husted, Steen; Lewis, Basil S; McMurray, John J V; Pais, Prem; Pouleur, Hubert; Steg, Philippe Gabriel; Verheugt, Freek W A; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars

    2014-01-01

    We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91%, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10% vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78%, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.

  17. Can I stop the warfarin? A review of the risks and benefits of discontinuing anticoagulation.

    Science.gov (United States)

    Spiess, Jeffrey L

    2009-01-01

    Long-term anticoagulant therapy with warfarin is part of standard therapy for several disorders commonly present in patients seen in hospice and palliative care programs. Yet warfarin is also the drug most implicated in adverse drug reactions and its risks rise with increasing age and comorbidity. Clinicians caring for patients with multiple comorbidities or a limited life expectancy often are faced with the decision as to whether anticoagulation should be continued. Published guidelines for the use of warfarin in venous thromboembolism and nonvalvular atrial fibrillation are based on studies in which such patients were underrepresented or excluded. Our review of the randomized trials on which these guidelines are based shows that the annual risk of recurrent venous thromboembolism after stopping warfarin is 2%-10%. No similar evidence is available for patients with atrial fibrillation, but the published CHADS(2) index uses multiple factors to estimate stroke risk. The risk of bleeding complications with warfarin is most closely linked to degree of anticoagulation. Nutritional compromise and changes in drug therapy increase this risk and require that any patient remaining on warfarin must undergo frequent monitoring of anticoagulant effect.

  18. AREDS Formula, Warfarin, and Bleeding: A Case Report from the Michigan Anticoagulation Quality Improvement Initiative

    Directory of Open Access Journals (Sweden)

    Eric Puroll

    2014-01-01

    Full Text Available Importance. The anticoagulant warfarin has been shown to interact with other medications, vitamin K containing foods, and over-the-counter products. These interactions may inhibit or potentiate the effect of warfarin, resulting in serious clotting or bleeding events. Observations. We report the case of an 84-year-old woman with atrial fibrillation, prescribed warfarin in May 2010 for stroke prevention. Her international normalized ratio (INR was stable until April 2013, when she was prescribed AREDS (Age Related Eye Disease Study formula pills, an eye vitamin compound, to slow the progression of age-related macular degeneration. This change was not reported to the Anticoagulation Service. Eighteen days later, she presented to the ED with groin and back pain and an INR of 10.4. An abdominal CT revealed a retroperitoneal hemorrhage with extension in multiple muscles. Both warfarin and AREDS were discontinued and the patient was discharged to subacute rehabilitation. This case was reviewed by the Anticoagulation Service and actions were taken to prevent similar adverse events. Conclusions. This report provides an example of the potential danger of supplement use, in this case, AREDS formula, in patients prescribed warfarin, and the importance of communicating medication changes to the providers responsible for warfarin management.

  19. Molecular displacement of warfarin from human serum albumin by flavonoid aglycones

    Energy Technology Data Exchange (ETDEWEB)

    Poór, Miklós [Institute of Laboratory Medicine, University of Pécs, Pécs H-7624 (Hungary); Li, Yin; Kunsági-Máté, Sándor [Department of General and Physical Chemistry, University of Pécs, Pécs H-7624 (Hungary); János Szentágothai Research Center, H-7624 Pécs (Hungary); Petrik, József [Department of Medical Biochemistry and Hematology, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb (Croatia); Vladimir-Knežević, Sanda [Department of Pharmacognosy, Faculty of Pharmacy and Biochemistry, University of Zagreb, HR-10000 Zagreb (Croatia); Kőszegi, Tamás, E-mail: koszegit@freemail.hu [Institute of Laboratory Medicine, University of Pécs, Pécs H-7624 (Hungary)

    2013-10-15

    The well-known 4-hydroxycoumarin derivative warfarin is a widespread anticoagulant drug. Besides its strong albumin binding property warfarin has a narrow therapeutic window. Therefore, a few percent of displacement from albumin can result in serious biological consequences. The flavonoid molecular group also shows very strong plasma albumin binding characteristics occupying the same binding site. It is plausible to hypothesize that flavonoid aglycones may be able to displace warfarin from human serum albumin (HSA). In our study the competing activities of different flavone (acacetin, apigenin, chrysin, luteolin), flavonol (galangin, quercetin) and flavanone (hesperetin, naringenin) aglycones were investigated using fluorescence spectroscopy. Our results represent that flavonoids are able to displace warfarin from the surface of HSA. On the other hand, when comparing flavone or flavonol groups to flavanones the latter group seems to be much weaker competitor. These observations were also supported by calculation of stability constants. Our investigations strongly suggest that we should reckon with the described molecular displacement. However, further in vivo studies are needed to support the findings of our model system. -- Highlights: • Various flavonoids are able to displace warfarin from human serum albumin. • Flavones and flavonols are much more effective competitors than flavanones. • Even 300 nM aglycone concentrations show the interaction with 3 μM warfarin. • Flavonoid pairs show quasi-additive desorbing property. • Flavones and flavonols are much stronger competitors than the examined drugs.

  20. Molecular displacement of warfarin from human serum albumin by flavonoid aglycones

    International Nuclear Information System (INIS)

    Poór, Miklós; Li, Yin; Kunsági-Máté, Sándor; Petrik, József; Vladimir-Knežević, Sanda; Kőszegi, Tamás

    2013-01-01

    The well-known 4-hydroxycoumarin derivative warfarin is a widespread anticoagulant drug. Besides its strong albumin binding property warfarin has a narrow therapeutic window. Therefore, a few percent of displacement from albumin can result in serious biological consequences. The flavonoid molecular group also shows very strong plasma albumin binding characteristics occupying the same binding site. It is plausible to hypothesize that flavonoid aglycones may be able to displace warfarin from human serum albumin (HSA). In our study the competing activities of different flavone (acacetin, apigenin, chrysin, luteolin), flavonol (galangin, quercetin) and flavanone (hesperetin, naringenin) aglycones were investigated using fluorescence spectroscopy. Our results represent that flavonoids are able to displace warfarin from the surface of HSA. On the other hand, when comparing flavone or flavonol groups to flavanones the latter group seems to be much weaker competitor. These observations were also supported by calculation of stability constants. Our investigations strongly suggest that we should reckon with the described molecular displacement. However, further in vivo studies are needed to support the findings of our model system. -- Highlights: • Various flavonoids are able to displace warfarin from human serum albumin. • Flavones and flavonols are much more effective competitors than flavanones. • Even 300 nM aglycone concentrations show the interaction with 3 μM warfarin. • Flavonoid pairs show quasi-additive desorbing property. • Flavones and flavonols are much stronger competitors than the examined drugs

  1. Possible interaction of warfarin with peppermint herbal tea: a case report

    Directory of Open Access Journals (Sweden)

    Aliasghar Moeinipour

    2017-06-01

    Full Text Available Herbal medicine is usually safe and popular in Iranian communities. Peppermint herbal products may interact with warfarin, which is an essential lifelong drug used in patients with prosthetic heart valves. Herein, we report a case of possible interaction between warfarin and peppermint herbal tea.We described a 68-year-old woman who was on warfarin treatment due to bileaflet mechanical aortic valve, and mitral valve replacement presented with severe dyspnea in the setting of large obstructive prosthetic mitral valve thrombosis diagnosed by echocardiography. Therefore, cardiac surgery was conducted in the emergent setting. Warfarin was started the day after the procedure. She developed melena with a volatile and elevated international normalized ratio (INR of 4.8 and prothrombin time > 30 s on the 7th post-operation day. She reported no changes in drug or dietary habits except for drinking high amounts of peppermint tea the day before. After the discontinuation of warfarin and medical consultation for gastrointestinal bleeding, the INR level decreased to 1.8 within two days.Consumption of peppermint herbal products are usually safe; however, caution should be taken with patients under warfarin treatment. Full disclosure for patients on anticoagulant treatment is necessary before discharge and during clinical follow-up

  2. Enzyme-catalyzed Michael addition for the synthesis of warfarin and its determination via fluorescence quenching of L-tryptophan

    Science.gov (United States)

    Yuan, Yusheng; Yang, Liu; Liu, Shaopu; Yang, Jidong; Zhang, Hui; Yan, Jingjing; Hu, Xiaoli

    2017-04-01

    A sensitive fluorescence sensor for warfarin was proposed via quenching the fluorescence of L-tryptophan due to the interaction between warfarin and L-tryptophan. Warfarin, as one of the most effective anticoagulants, was designed and synthesized via lipase from porcine pancreas (PPL) as a biocatalyst to catalyze the Michael addition of 4-hydroxycoumarin to α, β-unsaturated enones in organic medium in the presence of water. Furthermore, the spectrofluorometry was used to detect the concentration of warfarin with a linear range and detection limit (3σ/k) of 0.04-12.0 μmol L- 1 (R2 = 0.994) and 0.01 μmol L- 1, respectively. Herein, this was the first application of bio-catalytic synthesis and fluorescence for the determination of warfarin. The proposed method was applied to determine warfarin of the drug in tablets with satisfactory results.

  3. Choosing a particular oral anticoagulant and dose for stroke prevention in individual patients with non-valvular atrial fibrillation: part 1

    NARCIS (Netherlands)

    Diener, H.C.; Aisenberg, J.; Ansell, J.; Atar, D.; Breithardt, G.; Eikelboom, J.; Ezekowitz, M.D.; Granger, C.B.; Halperin, J.L.; Hohnloser, S.H.; Hylek, E.M.; Kirchhof, P.; Lane, D.A.; Verheugt, F.W.A.; Veltkamp, R.; Lip, G.Y.

    2017-01-01

    Patients with atrial fibrillation (AF) have a high risk of stroke and mortality, which can be considerably reduced by oral anticoagulants (OAC). Recently, four non-vitamin-K oral anticoagulants (NOACs) were compared with warfarin in large randomized trials for the prevention of stroke and systemic

  4. Genetics and clinical response to warfarin and edoxaban in patients with venous thromboembolism.

    Science.gov (United States)

    Vandell, Alexander G; Walker, Joseph; Brown, Karen S; Zhang, George; Lin, Min; Grosso, Michael A; Mercuri, Michele F

    2017-11-01

    The aim of this study was to investigate whether genetic variants can identify patients with venous thromboembolism (VTE) at an increased risk of bleeding with warfarin. Hokusai-venous thromboembolism (Hokusai VTE), a randomised, multinational, double-blind, non-inferiority trial, evaluated the safety and efficacy of edoxaban versus warfarin in patients with VTE initially treated with heparin. In this subanalysis of Hokusai VTE, patients genotyped for variants in CYP2C9 and VKORC1 genes were divided into three warfarin sensitivity types (normal, sensitive and highly sensitive) based on their genotypes. An exploratory analysis was also conducted comparing normal responders to pooled sensitive responders (ie, sensitive and highly sensitive responders). The analysis included 47.7% (3956/8292) of the patients in Hokusai VTE. Among 1978 patients randomised to warfarin, 63.0% (1247) were normal responders, 34.1% (675) were sensitive responders and 2.8% (56) were highly sensitive responders. Compared with normal responders, sensitive and highly sensitive responders had heparin therapy discontinued earlier (p<0.001), had a decreased final weekly warfarin dose (p<0.001), spent more time overanticoagulated (p<0.001) and had an increased bleeding risk with warfarin (sensitive responders HR 1.38 [95% CI 1.11 to 1.71], p=0.0035; highly sensitive responders 1.79 [1.09 to 2.99]; p=0.0252). In this study, CYP2C9 and VKORC1 genotypes identified patients with VTE at increased bleeding risk with warfarin. NCT00986154. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  5. Educating patients about warfarin therapy using information technology: A survey on healthcare professionals’ perspectives

    Directory of Open Access Journals (Sweden)

    Mullan J

    2012-06-01

    Full Text Available Objective: To explore healthcare professionals’ views about the benefits and challenges of using information technology (IT resources for educating patients about their warfarin therapy.Methods: A cross-sectional survey of both community and hospital-based healthcare professionals (e.g., doctors, pharmacists and nurses involved using a purpose-designed questionnaire. The questionnaires were distributed using a multi-modal approach to maximise response rates.Results: Of the total 300 questionnaires distributed, 109 completed surveys were received (43.3% response rate. Over half (53.2% of the healthcare participants were aged between 40-59 years, the majority (59.5% of whom were female. Fifty nine (54.1% participants reported having had no access to warfarin-specific IT-based patient education resources, and a further 19 (38.0% of the participants who had IT-access reported that they never used such resources. According to the healthcare participants, the main challenges associated with educating their patients about warfarin therapy included: patient-related factors, such as older age, language barriers, cognitive impairments and/or ethnic backgrounds or healthcare professional factors, such as time constraints. The healthcare professionals reported that there were several aspects about warfarin therapy which they found difficult to educate their patients about which is why they identified computers and interactive touch screen kiosks as preferred IT devices to deliver warfarin education resources in general practices, hospital-based clinics and community pharmacies. At the same time, the healthcare professionals also identified a number of facilitators (e.g., to reinforce warfarin education, to offer reliable and easily comprehensible information and barriers (e.g., time and costs of using IT resources, difficulty in operating the resources that could impact on the effective implementation of these devices in educating patients about their

  6. Association Between Dabigatran vs Warfarin and Risk of Osteoporotic Fractures Among Patients With Nonvalvular Atrial Fibrillation.

    Science.gov (United States)

    Lau, Wallis C Y; Chan, Esther W; Cheung, Ching-Lung; Sing, Chor Wing; Man, Kenneth K C; Lip, Gregory Y H; Siu, Chung-Wah; Lam, Joanne K Y; Lee, Alan C H; Wong, Ian C K

    2017-03-21

    The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown. To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF. Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016. Dabigatran or warfarin use during the study period. Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated. Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 [95% CI, -0.38 to -0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 [95% CI, -2.40 to -3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 [95% CI, 0.67 to -0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand

  7. Preformulation study of the inclusion complex warfarin-beta-cyclodextrin.

    Science.gov (United States)

    Zingone, G; Rubessa, F

    2005-03-03

    Inclusion complex between warfarin and beta-cyclodextrin was obtained to improve the in vitro bioavailability of the drug in acidic media. Inclusion complexation in solution was studied by phase solubility technique. The apparent stability constant was influenced by the pH of the medium ranging from 633.26 M(-1) (at pH 1.2, where the drug was in unionised form) to 99.81 M(-1) (at pH 7.4, where the drug was in ionised form). Phase solubility study showed an AL-type diagram indicating the formation of an inclusion complex in 1:1 molar ratio. Solid binary mixtures of the drug with beta-cyclodextrin were prepared by several methods (physical mixing, kneading, co-evaporation, freeze-drying). Physicochemical characterizations were performed using differential scanning calorimetry, powder X-ray diffractometry and dissolution studies. Preparation method influenced the physicochemical properties of the binary mixtures. An inclusion complex was obtained by freeze-drying, and it showed a high solubility and drug dissolution rate. The physical stability of the complex was also studied. After one year storage in glass container at room temperature no significant changes were detected in the diffractogram, thermogram and dissolution profile of the freeze-dried product.

  8. Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics in the Treatment of Urinary Tract Infections.

    Science.gov (United States)

    Saum, Lindsay M; Balmat, Ryan P

    2016-04-01

    The cephalosporin class has been associated with an increased risk of bleeding among elderly patients receiving warfarin. Urinary tract infections (UTI) are the most prevalent infection in elderly patients. To determine the extent of interaction between antibiotics used in the treatment of UTI, particularly specific cephalosporins and warfarin. A retrospective chart review was conducted on chronic warfarin patients with a diagnosis of UTI treated with ceftriaxone, a first-generation cephalosporin, penicillin, or ciprofloxacin. The primary outcome was the comparison of the extent of international normalized ratio (INR) change from baseline between each antibiotic group. The ceftriaxone group was found to have a statistically significant higher peak INR value compared to all other studied antibiotics (ceftriaxone: 3.56, first-generation cephalosporins: 2.66, penicillins: 2.98, ciprofloxacin: 2.3; P = .004), a statistically significant greater extent of change in INR value (+1.19, +0.66, +0.8, +0.275; P = .006), and a statistically significant greater percentage change in INR value when compared to ciprofloxacin (54.4% vs 12.7%; P = .037). Ceftriaxone interacts with warfarin to increase a patient's INR value more than other commonly administered antibiotics for UTI treatment. Other antibiotics should be preferred for UTI treatment in patients on warfarin. © The Author(s) 2014.

  9. Cohort-specific imputation of gene expression improves prediction of warfarin dose for African Americans

    Directory of Open Access Journals (Sweden)

    Assaf Gottlieb

    2017-11-01

    Full Text Available Abstract Background Genome-wide association studies are useful for discovering genotype–phenotype associations but are limited because they require large cohorts to identify a signal, which can be population-specific. Mapping genetic variation to genes improves power and allows the effects of both protein-coding variation as well as variation in expression to be combined into “gene level” effects. Methods Previous work has shown that warfarin dose can be predicted using information from genetic variation that affects protein-coding regions. Here, we introduce a method that improves dose prediction by integrating tissue-specific gene expression. In particular, we use drug pathways and expression quantitative trait loci knowledge to impute gene expression—on the assumption that differential expression of key pathway genes may impact dose requirement. We focus on 116 genes from the pharmacokinetic and pharmacodynamic pathways of warfarin within training and validation sets comprising both European and African-descent individuals. Results We build gene-tissue signatures associated with warfarin dose in a cohort-specific manner and identify a signature of 11 gene-tissue pairs that significantly augments the International Warfarin Pharmacogenetics Consortium dosage-prediction algorithm in both populations. Conclusions Our results demonstrate that imputed expression can improve dose prediction and bridge population-specific compositions. MATLAB code is available at https://github.com/assafgo/warfarin-cohort

  10. Warfarin and Rivaroxaban Duplication: A Case Report and Medication Error Analysis.

    Science.gov (United States)

    Fusco, Julie A; Paulus, Eric J; Shubat, Alexandra R; Miah, Sharminara

    2015-12-01

    A 62-year-old African American man received unintentional duplicate anticoagulation therapy with warfarin 5 mg and rivaroxaban 20 mg daily for the treatment of recurrent pulmonary embolism. The patient presented to the anticoagulation clinic 6 days after hospital discharge with an International Normalized Ratio (INR) of 2.3 and he was instructed to continue warfarin 5 mg daily. Seven days later, he returned to the clinic with an INR >8.0 using a point-of-care device. He denied any signs or symptoms of bleeding. During the interview, he reported starting a new medication for neuropathy 5 days earlier. The clinical pharmacist contacted the dispensing pharmacy and determined rivaroxaban 20 mg was the new medication. The patient denied receiving new prescription counseling at the dispensing pharmacy. Because rivaroxaban can falsely elevate INR results, the actual INR value was unknown. To minimize the risk for recurrent venous thromboembolism, vitamin K was not administered and no warfarin doses were held. Rather, the patient was instructed to stop rivaroxaban and reduce the warfarin dose. Five days later, the patient returned with an INR of 4.3. He still had not experienced any signs or symptoms of bleeding. The patient was quickly stabilized on a warfarin maintenance dose of 22.5 mg weekly. The anticoagulation clinic pharmacist notified management at the clinic and at the dispensing pharmacy in an effort to identify process errors and prevent additional incidents.

  11. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial

    Science.gov (United States)

    Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D.; Hellkamp, Anne S.; Piccini, Jonathan P.; Stevens, Susanna R.; Lokhnygina, Yuliya; Patel, Manesh R.; Halperin, Jonathan L.; Singer, Daniel E.; Hankey, Graeme J.; Hacke, Werner; Becker, Richard C.; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2014-01-01

    Aims We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. Methods and results ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55–1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75–1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05–1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94–1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Conclusions Many patients with ‘non-valvular atrial fibrillation’ have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. PMID:25148838

  12. Clinical characteristics and outcomes with rivaroxaban vs. warfarin in patients with non-valvular atrial fibrillation but underlying native mitral and aortic valve disease participating in the ROCKET AF trial.

    Science.gov (United States)

    Breithardt, Günter; Baumgartner, Helmut; Berkowitz, Scott D; Hellkamp, Anne S; Piccini, Jonathan P; Stevens, Susanna R; Lokhnygina, Yuliya; Patel, Manesh R; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

    2014-12-14

    We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial. ROCKET AF excluded patients with mitral stenosis or artificial valve prostheses. We used Cox regression to adjust comparisons for potential confounders. Among 14 171 patients, 2003 (14.1%) had SVD; they were older and had more comorbidities than patients without SVD. The rate of stroke or systemic embolism with rivaroxaban vs. warfarin was consistent among patients with SVD [2.01 vs. 2.43%; hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.55-1.27] and without SVD (1.96 vs. 2.22%; HR 0.89, 95% CI 0.75-1.07; interaction P = 0.76). However, rates of major and non-major clinically relevant bleeding with rivaroxaban vs. warfarin were higher in patients with SVD (19.8% rivaroxaban vs. 16.8% warfarin; HR 1.25, 95% CI 1.05-1.49) vs. those without (14.2% rivaroxaban vs. 14.1% warfarin; HR 1.01, 95% CI 0.94-1.10; interaction P = 0.034), even when controlling for risk factors and potential confounders. In intracranial haemorrhage, there was no interaction between patients with and without SVD where the overall rate was lower among those randomized to rivaroxaban. Many patients with 'non-valvular atrial fibrillation' have significant valve lesions. Their risk of stroke is similar to that of patients without SVD after controlling for stroke risk factors. Efficacy of rivaroxaban vs. warfarin was similar in patients with and without SVD; however, the observed risk of bleeding was higher with rivaroxaban in patients with SVD but was the same among those without SVD. Atrial fibrillation patients with and without SVD experience the same stroke-preventive benefit of oral anticoagulants. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  13. Venous Thromboembolism Prophylaxis After TKA: Aspirin, Warfarin, Enoxaparin, or Factor Xa Inhibitors?

    Science.gov (United States)

    Bala, Abiram; Huddleston, James I; Goodman, Stuart B; Maloney, William J; Amanatullah, Derek F

    2017-09-01

    There is considerable debate regarding the ideal agent for venous thromboembolism (VTE) prophylaxis after TKA. Numerous studies and meta-analyses have yet to provide a clear answer and often omit one or more of the commonly used agents such as aspirin, warfarin, enoxaparin, and factor Xa inhibitors. Using a large database analysis, we asked: (1) What are the differences in VTE incidence in primary TKA after administration of aspirin, warfarin, enoxaparin, or factor Xa inhibitors? (2) What are the differences in bleeding risk among these four agents? (3) How has use of these agents changed with time? We queried a combined Humana and Medicare database between 2007 and Quarter 1 of 2016, and identified all primary TKAs performed using ICD-9 and Current Procedural Terminology codes. All patients who had any form of antiplatelet or anticoagulation prescribed within 1 year before TKA were excluded from our study cohort. We then identified patients who had either aspirin, warfarin, enoxaparin, or factor Xa inhibitors prescribed within 2 weeks of primary TKA. Each cohort was matched by age and sex. Elixhauser comorbidities and Charlson Comorbidity Index for each group were calculated. We identified 1016 patients with aspirin, and age- and sex-matched 6096 patients with enoxaparin, 6096 patients with warfarin, and 5080 patients with factor Xa inhibitors. Using ICD-9 codes, with the understanding that patients at greater risk may have had more-attentive surveillance, the incidence of postoperative deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding-related complications (bleeding requiring surgical intervention, hemorrhage, hematoma, hemarthrosis), postoperative anemia, and transfusion were identified at 2 weeks, 30 days, 6 weeks, and 90 days postoperatively. A four-way chi-squared test was used to determine statistical significance. Utilization was calculated using compound annual growth rate. There was a difference in the incidence of DVT at 90 days (p aspirin

  14. Comparison of Warfarin Requirements in Post-cardiac Surgery Patients: Valve Replacement Versus Non-valve Replacement.

    Science.gov (United States)

    Olson, Logan M; Nei, Andrea M; Joyce, David L; Ou, Narith N; Dierkhising, Ross A; Nei, Scott D

    2018-01-11

    Anticoagulation with warfarin affects approximately 140,000 post-cardiac surgery patients every year, yet there remains limited published data in this patient population. Dosing remains highly variable due to intrinsic risk factors that plague cardiac surgery candidates and a lack of diverse literature that can be applied to those who have undergone a cardiac surgery alternative to heart valve replacement (HVR). In the present study, our aim was to compare the warfarin requirements between HVR and non-HVR patients. This was a single-center, retrospective study of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October 31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac surgeries. A total of 683 patients were assessed during the study period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A multivariable analysis was performed to adjust for gender, age, body mass index and drug interactions. This was the largest study to evaluate warfarin dose requirements in post-cardiac surgery patients and is the first to compare warfarin requirements between HVR and non-HVR patients during the immediate post-operative period. Both groups had similar warfarin requirements, which supports expanding the initial warfarin dosing recommendations of the 9th edition Chest guideline to include non-HVR patients as well as HVR patients.

  15. Effect of Ankaferd Blood Stopper on Skin Superoxide Dismutase and Catalase Activities in Warfarin-Treated Rats.

    Science.gov (United States)

    Aktop, Sertaç; Emekli-Alturfan, Ebru; Gönül, Onur; Göçmen, Gökhan; Garip, Hasan; Yarat, Ayşen; Göker, Kamil

    2017-03-01

    Ankaferd Blood Stopper (ABS) is a new promising local hemostatic agent, and its mechanism on hemostasis has been shown by many studies. However, the effects of ABS on skin superoxide dismutase (SOD) and catalase (CAT) activities have not been investigated before. The aim of this study was to evaluate the effects of this new generation local hemostatic agent on warfarin-treated rats focusing on its the antioxidant potential in short-term soft tissue healing. Twelve systemically warfarin treated (warfarin group) and 12 none treated Wistar Albino rats (control group) were selected for the trial. Rats in the warfarin group were treated intraperitonally with 0.1 mg/kg warfarin, and rats in the control group were given 1 mL/kg saline 3 days earlier to surgical procedure and continued until killing. All rats had incisions on dorsal dermal tissue, which was applied ABS or no hemostatic agent before suturing. Six of each group were killed on day 4, and the other 6 were killed on day 8. Blood and skin samples were taken. Prothrombin time (PT) in blood samples, CAT, and SOD activities in skin samples were determined. Warfarin treatment dose was found to be convenient and warfarin treatment increased the PT levels as expected. Warfarin treatment decreased CAT activity significantly compared to the control group. The ABS treatment significantly increased SOD activities in the warfarin group at the end of the eighth day. Ankaferd Blood Stopper acted positively in short-term tissue healing by increasing SOD activity in warfarin-treated rats. Therefore, ABS may be suggeted as a promoting factor in tissue healing.

  16. Comparison of initial loading doses of 5 mg and 10 mg for warfarin therapy

    Directory of Open Access Journals (Sweden)

    Sidnei Lastória

    2014-03-01

    Full Text Available CONTEXT: The question of what is the best loading dosage of warfarin when starting anticoagulant treatment has been under discussion for ten years. We were unable to find any comparative studies of these characteristics conducted here in Brazil. OBJECTIVE: To compare the safety and efficacy of two initial warfarin dosage regimens for anticoagulant treatment. METHODS: One-hundred and ten consecutive patients of both sexes, with indications for anticoagulation because of venous or arterial thromboembolism, were analyzed prospectively. During the first 3 days of treatment, these patients were given adequate heparin to keep aPTT (activated partial thromboplastin time between 1.5 and 2.5, plus 5 mg of warfarin. From the fourth day onwards, their warfarin doses were adjusted using International Normalized Ratios (INR; target range: 2 to 3. This prospective cohort was compared with a historical series of 110 patients had been given 10 mg of warfarin on the first 2 days and 5 mg on the third day with adjustments based on INR thereafter. Outcomes analyzed were as follows: recurrence of thromboembolism, bleeding events and time taken to enter the therapeutic range. RESULTS: Efficacy, safety and length of hospital stay were similar in both samples. The sample that were given 10 mg entered the therapeutic range earlier (means: 4.5 days vs. 5.8 days, were on lower doses at discharge and had better therapeutic indicators at the first return appointment. CONCLUSIONS: The 10 mg dosage regimen took less time to attain the therapeutic range and was associated with lower warfarin doses at discharge and better INR at first out-patients follow-up visit.

  17. Risk of Venous Thromboembolism After Receiving Prothrombin Complex Concentrate for Warfarin-associated Intracranial Hemorrhage.

    Science.gov (United States)

    Felton, Diana; Foley, Elizabeth M; Traub, Stephen J; Vodonos, Alina; Ganetsky, Michael

    2016-01-01

    Prothrombin complex concentrates (PCCs) are commonly used to rapidly reverse warfarin-associated coagulopathy; however, venous thromboembolism (VTE) is an established adverse event. To determine risk factors for VTE AFTER administration of a three-factor prothrombin complex concentrate (3F-PCC) for warfarin-associated intracranial hemorrhage (ICH). Retrospective chart review of all patients with a warfarin-associated ICH who received a 3F-PCC at a single tertiary care hospital between 2008 and 2013. Outcomes were VTE events (defined as deep vein thrombosis [DVT], pulmonary embolism [PE], limb ischemia, transient ischemic attack, cerebrovascular accident, non-ST-segment elevation myocardial infarction, ST-segment elevation myocardial infarction, and unexplained sudden death) occurring within 30 days of 3F-PCC administration. Risk factors in subjects with and without VTE complications were compared via Fisher's exact test, Student's t-test, Mann-Whitney U test, and univariate logistic regression as appropriate. Two hundred nine subjects received 3F-PCC for warfarin-associated ICH. There were 22 VTE events in 19 subjects (9.1%). Baseline characteristics of subjects with and without VTE were similar. There was a significant increase in VTE events in 29 subjects who were taking warfarin for a previous PE or DVT (36.8% vs. 11.6%, p = 0.007; logistic regression odds ratio 4.455, p = 0.005). Patients with a prior history of PE or DVT who were given 3F-PCC for warfarin-associated ICH were 4.5 times more likely to sustain a VTE within 30 days. A careful analysis of risks and benefits of rapidly reversing anticoagulation must be made prior to the administration of 3F-PCC in this patient population. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Contribution of rivaroxaban to the international normalized ratio when switching to warfarin for anticoagulation as determined by simulation studies.

    Science.gov (United States)

    Siegmund, Hans-Ulrich; Burghaus, Rolf; Kubitza, Dagmar; Coboeken, Katrin

    2015-06-01

    This study evaluated the influence of rivaroxaban 20 mg once daily on international normalized ratio (INR) during the co-administration period when switching from rivaroxaban to warfarin. We developed a calibrated coagulation model that was qualified with phase I clinical data. Prothrombin time and INR values were simulated by use of phospholipid concentrations that matched Neoplastin Plus® and Innovin® reagents. To simulate the combined effects of rivaroxaban and warfarin on INR during switching, warfarin initiation was simulated by adjusting the magnitude of the warfarin effect to reach the desired target INRs over the course of 21 days. The warfarin effect values (obtained every 6 h) and the desired rivaroxaban plasma concentrations were used. Nomograms were generated from rivaroxaban induced increases in INR. The simulation had good prediction quality. Rivaroxaban induced increases in the total INR from the warfarin attributed INR were seen, which increased with rivaroxaban plasma concentration. When the warfarin only INR was 2.0-3.0, the INR contribution of rivaroxaban with Neoplastin Plus® was 0.5-1.2, decreasing to 0.3-0.6 with Innovin® at median trough rivaroxaban plasma concentrations (38 μg l(-1) ). The data indicate that measuring warfarin induced changes in INR are best performed at trough rivaroxaban concentrations (24 h after rivaroxaban dosing) during the co-administration period when switching from rivaroxaban to warfarin. Furthermore, Innovin® is preferable to Neoplastin Plus® because of its substantially lower sensitivity to rivaroxaban, thereby reducing the influence of rivaroxaban on the measured INR. © 2014 The British Pharmacological Society.

  19. Biopsy of the prostate guided by transrectal ultrasound: relation between warfarin use and incidence of bleeding complications

    Energy Technology Data Exchange (ETDEWEB)

    Ihezue, C.U. [Department of Radiology, Southampton General Hospital (United Kingdom); Smart, J. [Department of Radiology, Southampton General Hospital (United Kingdom); Dewbury, K.C. [Department of Radiology, Southampton General Hospital (United Kingdom)]. E-mail: keith.dewbury@suht.swest.nhs.uk; Mehta, R. [Department of Radiology, Southampton General Hospital (United Kingdom); Burgess, L. [Department of Radiology, Southampton General Hospital (United Kingdom)

    2005-04-01

    AIM: To determine the relation between warfarin use and the frequency of bleeding complications after biopsy of the prostate guided by transrectal ultrasound (TRUS). METHODS: Overall, 1022 consecutive patients with suspected prostatic disease were followed after biopsy. Warfarin and aspirin use was determined on the day of the procedure. A TRUS-guided biopsy was performed and patients were offered a questionnaire to complete 10 days after the procedure, to determine any immediate or delayed bleeding complications. Follow-up telephone calls were made to those who had not replied within the stipulated period. RESULTS: Of the 1000 patients who replied, 49 were receiving warfarin, 220 were receiving aspirin and 731 were not receiving any anticoagulant drugs. Of the 49 subjects reporting current use of warfarin, 18 (36.7%) experienced haematuria, compared with 440 (60.2%) of the patients receiving no anti-coagulant drugs who reported haematuria. This was statistically significant (p=0.001). Of the group receiving warfarin, 4 (8.2%) experienced haematospermia whereas 153 (21%) of the group receiving no anticoagulant medication reported haematospermia. This difference also was statistically significant (p=0.030). Rectal bleeding was experienced by 7 (14.3%) of the group receiving warfarin compared with 95 (13%) in the group without anticoagulant medication, but this was not statistically significant (p=0.80). We also demonstrated that there was no statistically significant association between the severity of the bleeding complications and medication with warfarin. CONCLUSION: None of the group receiving warfarin experienced clinically important bleeding complications. Our results suggest that the frequency and severity of bleeding complications were no worse in the warfarin group than in the control group and that discontinuing anticoagulation medication before prostate biopsy may be unnecessary.

  20. Impact of Computer-Aided Warfarin Dosing in a Saudi Arabian ...

    African Journals Online (AJOL)

    Purpose: To compare the efficacy of computer-aided dosing using Coagclinic (a web-based software) with physician dosing in patients receiving warfarin for various cardiac indications. Methods: In order to calculate the effectiveness of physician managed anticoagulation dosing, we calculated the “percentage of time ...

  1. Treatment of acute venous thromboembolism with dabigatran or warfarin and pooled analysis

    NARCIS (Netherlands)

    Schulman, Sam; Kakkar, Ajay K.; Goldhaber, Samuel Z.; Schellong, Sebastian; Eriksson, Henry; Mismetti, Patrick; Christiansen, Anita Vedel; Friedman, Jeffrey; Le Maulf, Florence; Peter, Nuala; Kearon, Clive; Schulman, S.; Eriksson, H.; Goldhaber, S.; Kakkar, A.; Kearon, C.; Mismetti, P.; Schellong, S.; Bergqvist, D.; Tijssen, J.; Prins, M. [=Martin H.; Robben, S.; Büller, H.; Otten, H. M.; Brandjes, D.; Peters, R.; Mac Gillavry, M. R.; Gan, E.; Salem, H.; Baker, R.; Blomberry, P.; Curnow, J.; Annichino-Bizzacch, J. M.; Brandao Panico, M. D.; Timi Ribas, J. R.; Fernandes Manenti, E. R.; Miranda, F.; Moraes, J.; Raev, D.; Mollov, M.; Peneva, M.; Milanov, S.; Anderson, D.; Crowther, M.; Dolan, S.; Eikelboom, J.; Game, M.; Kahn, S.; Kassis, J.; Ritchie, B.; Solymoss, S.; Rodger, M.; Yeo, E.; Milot, A.; Klinke, P.; Chen, W.; Zhihong, L.; Chunxue, B.; Jinming, L.; Jiwei, Z.; Jie, C.; Jina, K.; Yuqi, W.; Zhongqi, Y.; Hua, W.; Kejing, Y.; Bonan, L.; Yadong, Y.; Changwei, L.; Jin, Z.; Yongcheng, D.; Spinar, J.; Maly, R.; Cizek, V.; Bercikova, J.; Cervinka, P.; Lang, P.; Jirka, V.; Oral, I.; Reichert, P.; Kotik, L.; Pojsl, S.; Klimovic, T.; Husted, S.; Nielsen, H.; Friis, E.; Skødebjerg Kristensen, K.; Mottier, D.; El Kouri, D.; Bleher, Y.; Leroux, L.; Boda, Z.; Sereg, M.; Riba, M.; Hiremath, J. S.; Kareem, S.; Banker, D. N.; Gadkari, M.; Parakh, R.; Suresh, K. R.; Natarajan, S.; Jain, A.; Aggarwal, P. K.; Patil, C. B.; Durairaj, N.; Seshadri, R.; Thakore, V. M.; Rai, K. M.; Efrati, S.; Elias, M.; Gavish, D.; Grossman, M.; Lishner, M.; Lahavr, M.; Lugassy, G.; Nseir, W.; Zeltser, D.; Brenner, B.; Yeganeh, S.; Zanatta, N.; Pizzini, A. M.; Di Salvo, M.; Novo, S.; Arosio, E.; Campanini, M.; Castellani, S.; Oh, D. Y.; Cho, D. K.; Kim, D. I.; Kwon, T. W.; Yoon, S. S.; Kim, M. H.; Kwon, S. Y.; Cheong, J. W.; Lee, T. S.; Shokri, A. A.; Looi, T. S.; Chon, Y.; Chunn, K. Y.; Salleh, R.; Fijnheer, R.; Veth, G.; Dees, A.; Pruijt, H.; Lieverse, A. G.; Jie, G. K. S.; van Marwijk-Kooij, M.; Simsek, S.; Hanna, M.; Jackson, S.; Ockelford, P.; Smith, M.; Sandset, P. M.; Waage, A.; Fernandez, L.; Ma, A.; de Guia, T.; Ong-Garcia, H.; Lach, L.; Zawilska, K.; Gluszek, S.; Czarnobilski, K.; Gaciong, Z.; Chernyatina, M.; Tchumakov, A.; Staroverov, I.; Belentsov, S.; Katelnitsky, I.; Khamitov, A.; Zaporozhsky, A.; Degterev, M.; Khitaryan, A.; Heng, L. L.; Robless, P. A.; Kenny, S. Y. K.; Poliacik, P.; Duris, T.; Szentivanyi, M.; Zubek, V.; Adler, D.; Smith, C.; Roux, D. Le; van Rensburg, J.; Miller, D.; Ismail, S.; Roodt, A.; Vermooten, I. H.; Villalta, J.; Nieto, J. A.; Trujillo, J.; del Toro, J.; García Fuster, M. J.; Giménez, A.; Lozano, P.; Holmström, M.; Edmark, M.; Carlsson, A.; Torstensson, I.; Huang, C. H.; Shyu, K. G.; Chiang, C. E.; Shen, M. C.; Tsai, C. S.; Wang, S. S.; Sirijerachai, C.; Saetang, S.; Kanitsap, N.; Polprasert, C.; Mutirangura, P.; Boonbaichaiyapruck, S.; Leelasiri, A.; Kurtoglu, M.; Eren, E.; Bengisun, U.; Sakinci, U.; Karahan, S.; Islamoglu, F.; Kurt, N.; Aygun, E.; Skupyy, O.; Keeling, D.; Kesteven, P.; Cohen, A.; Maclean, R.; Thomas, W.; Masson, J. A.; Bolster, E.; Beard, T.; Gasparis, A.; LaPerna, L. M.; Gibson, K.; Curtis, B.; Chu, C. O.; Bass, P.; Lavende, R.

    2014-01-01

    Dabigatran and warfarin have been compared for the treatment of acute venous thromboembolism (VTE) in a previous trial. We undertook this study to extend those findings. In a randomized, double-blind, double-dummy trial of 2589 patients with acute VTE treated with low-molecular-weight or

  2. A re-appraisal of Warfarin control in the treatment of Deep Vein ...

    African Journals Online (AJOL)

    Background: Warfarin is commonly used for management of deep vein thrombosis (DVT) and pulmonary embolism (PE), controlling therapy by means of the International Normalized Ratio (INR). Objectives: To identify differences in INR results between patients with thromboembolic and haemorrhagic complications and ...

  3. A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics.

    Directory of Open Access Journals (Sweden)

    Jorge Duconge

    Full Text Available This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients.A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals.The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R2 = 0.70, MAE = 0.72mg/day than a clinical algorithm that excluded genotypes and admixture (R2 = 0.60, MAE = 0.99mg/day, and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001. The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias.Results supported our rationale to incorporate individual's genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics.ClinicalTrials.gov NCT01318057.

  4. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack

    DEFF Research Database (Denmark)

    Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia

    2012-01-01

    In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy...

  5. A race-specific interaction between vitamin K status and statin use during warfarin therapy initiation

    Science.gov (United States)

    Vitamin K (VK) is required for the post-translational modification of several clotting factors. Warfarin is a vitamin K antagonist and anticoagulant. The most common dietary and circulating form of VK is phylloquinone (PK). PK is lipid soluble, carried by triglyceride-rich lipoproteins, and shares a...

  6. A Green, Enantioselective Synthesis of Warfarin for the Undergraduate Organic Laboratory

    Science.gov (United States)

    Wong, Terence C.; Sultana, Camille M.; Vosburg, David A.

    2010-01-01

    The enantioselective synthesis of drugs is of fundamental importance in the pharmaceutical industry. In this experiment, students synthesize either enantiomer of warfarin, a widely used anticoagulant, in a single step from inexpensive starting materials. Stereoselectivity is induced by a commercial organocatalyst, ("R","R")- or…

  7. Lipase-supported metal-organic framework bioreactor catalyzes warfarin synthesis.

    Science.gov (United States)

    Liu, Wan-Ling; Yang, Ni-Shin; Chen, Ya-Ting; Lirio, Stephen; Wu, Cheng-You; Lin, Chia-Her; Huang, Hsi-Ya

    2015-01-02

    A green and sustainable strategy synthesizes clinical medicine warfarin anticoagulant by using lipase-supported metal-organic framework (MOF) bioreactors (see scheme). These findings may be beneficial for future studies in the industrial production of chemical, pharmaceutical, and agrochemical precursors. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Development of predictive models for estimating warfarin maintenance dose based on genetic and clinical factors.

    Science.gov (United States)

    Yang, Lu; Linder, Mark W

    2013-01-01

    In this chapter, we use calculation of estimated warfarin maintenance dosage as an example to illustrate how to develop a multiple linear regression model to quantify the relationship between several independent variables (e.g., patients' genotype information) and a dependent variable (e.g., measureable clinical outcome).

  9. New oral anticoagulants for atrial fibrillation: a review of clinical trials.

    Science.gov (United States)

    O'Dell, Kate M; Igawa, Daniel; Hsin, Jerline

    2012-04-01

    Warfarin had been the only oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF) for decades. Direct thrombin inhibitors and factor Xa inhibitors are new anticoagulants recently approved for prevention of stroke or systemic embolism in patients with AF. The aim of this article was to provide a systematic review of recently published clinical data on the direct thrombin inhibitors and factor Xa inhibitors in the management of AF. A search of the ClinicalTrials.gov registry was conducted using the subject terms dabigatran, rivaroxaban, and apixaban. Each search was limited to clinical trials that included patients with AF. Completed studies with warfarin as the main comparator were identified. From the yielded results, the national clinical trial identifier was inputted in PubMed (1966-November 2011) for a search of published literature. Three Phase III clinical trials reported the efficacy of each agent in patients who have AF and risk factors for stroke or embolic complications. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study reported dabigatran 150 mg was associated with a lower rate of stroke and systemic embolism, whereas dabigatran 110 mg was associated with a similar rate for such events when compared with warfarin (relative risk = 0.66; 95% confidence interval [CI], 0.53-0.82; P Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, rivaroxaban was reported to be noninferior to warfarin in reducing stroke or systemic embolism (2.1% vs 2.4% per year; hazard ratio = 0.88; 95% CI, 0.75-1.03; P trial reported that apixaban reduced stroke or systemic embolic events by 21% when compared with warfarin (1.27% vs 1.60% per year, respectively; hazard ratio = 0.79; 95% CI, 0.66-0.95; P < 0.001). All 3 agents were associated with similar bleeding when compared with warfarin. Published data suggest that all 3 agents

  10. Direct oral anticoagulants for secondary prevention in patients with non-valvular atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2013-12-01

    Full Text Available The patients with non-valvular atrial fibrillation (NVAF, both permanent and paroxysmal, and history of previous transient ischemic attack (TIA or stroke represent a category of patients at high risk of new embolic events, independently of the presence of other risk factors. In these patients, national and international guidelines recommend oral anticoagulants as first choice for antithrombotic prevention. Direct oral anticoagulants (DOACs have been demonstrated to be not inferior to warfarin for many end points in NVAF patients in terms of efficacy and safety. The post hoc analysis in selected subgroups of patients enrolled in the three mega trials of phase III comparing DOACs (RE-LY, ROCKET-AF and ARISTOTLE with warfarin help to evaluate whether superiority and non-inferiority persist in these subgroups. Here, patients with NVAF and history of previous TIA/stroke receiving DOACs as secondary prevention are compared with patients with the same characteristics receiving warfarin. An analysis of these patients has been recently published (separately for each of three DOACs. This analysis shows that DOACs maintain their non-inferiority when compared with warfarin in secondary prevention, representing a real alternative in this context of patients at high risk for ischemic and bleeding events.

  11. Direct-Acting Oral Anticoagulants: Practical Considerations for Emergency Medicine Physicians

    Directory of Open Access Journals (Sweden)

    W. Frank Peacock

    2016-01-01

    Full Text Available Nonvalvular atrial fibrillation- (NVAF- related stroke and venous thromboembolism (VTE are cardiovascular diseases associated with significant morbidity and economic burden. The historical standard treatment of VTE has been the administration of parenteral heparinoid until oral warfarin therapy attains a therapeutic international normalized ratio. Warfarin has been the most common medication for stroke prevention in NVAF. Warfarin use is complicated by a narrow therapeutic window, unpredictable dose response, numerous food and drug interactions, and requirements for frequent monitoring. To overcome these disadvantages, direct-acting oral anticoagulants (DOACs—dabigatran, rivaroxaban, apixaban, and edoxaban—have been developed for the prevention of stroke or systemic embolic events (SEE in patients with NVAF and for the treatment of VTE. Advantages of DOACs include predictable pharmacokinetics, few drug-drug interactions, and low monitoring requirements. In clinical studies, DOACs are noninferior to warfarin for the prevention of NVAF-related stroke and the treatment and prevention of VTE as well as postoperative knee and hip surgery VTE prophylaxis, with decreased bleeding risks. This review addresses the practical considerations for the emergency physician in DOAC use, including dosing recommendations, laboratory monitoring, anticoagulation reversal, and cost-effectiveness. The challenges of DOACs, such as the lack of specific laboratory measurements and antidotes, are also discussed.

  12. Effectiveness and outcome of management strategies for dabigatran- or warfarin-related major bleeding events.

    Science.gov (United States)

    Majeed, Ammar; Hwang, Hun-Gyu; Eikelboom, John W; Connolly, Stuart; Wallentin, Lars; Feuring, Martin; Brueckmann, Martina; Noack, Herbert; Yusuf, Salim; Schulman, Sam

    2016-04-01

    Strategies used for the management of dabigatran-related major bleeding events (MBEs), and their effectiveness have not been systematically evaluated. Reports on 1034 individuals experiencing 1121 MBEs (696 on dabigatran, and 425 on warfarin) in 5 phase III randomized controlled trials were assessed independently by two investigators. MBEs were managed either by drug discontinuation only (37%), or drug discontinuation with either transfusion of only red cell concentrates (38%), or plasma (23%). Few MBEs (2%) were treated with coagulation factor concentrates. The effectiveness of the management was assessed as good in significantly larger proportion of MBEs on dabigatran (91%) than on warfarin (84%, odds ratio [OR] 1.68; 95% confidence interval [CI], 1.14-2.49), which was consistent with the lower 30-day mortality (OR (OR 0.66; 95% CI, 0.44-1.00)). The effectiveness of bleeding management in non-traumatic bleeding was better in patients with dabigatran than with warfarin (OR 1.82; 95% CI, 1.18-2.79) but was similar in traumatic bleeding (OR 0.75; 95% CI, 0.25-2.30). The relative effectiveness of management of bleeding and 30-day mortality rates across other key subgroups of patients or sites of bleeding, the use of platelet inhibitors, age-, sex- and renal function subgroups, were comparable in MBEs on dabigatran or warfarin. Despite the unavailability of a specific antidote at the time of these studies, bleeding in patients receiving dabigatran was managed in the overwhelming majority of patients without coagulation factor concentrates, with comparable or superior effectiveness and lower 30-day mortality rates versus those who bleed while receiving warfarin. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Influence of Genotype on Warfarin Maintenance Dose Predictions Produced Using a Bayesian Dose Individualization Tool.

    Science.gov (United States)

    Saffian, Shamin M; Duffull, Stephen B; Roberts, Rebecca L; Tait, Robert C; Black, Leanne; Lund, Kirstin A; Thomson, Alison H; Wright, Daniel F B

    2016-12-01

    A previously established Bayesian dosing tool for warfarin was found to produce biased maintenance dose predictions. In this study, we aimed (1) to determine whether the biased warfarin dose predictions previously observed could be replicated in a new cohort of patients from 2 different clinical settings, (2) to explore the influence of CYP2C9 and VKORC1 genotype on predictive performance of the Bayesian dosing tool, and (3) to determine whether the previous population used to develop the kinetic-pharmacodynamic model underpinning the Bayesian dosing tool was sufficiently different from the test (posterior) population to account for the biased dose predictions. The warfarin maintenance doses for 140 patients were predicted using the dosing tool and compared with the observed maintenance dose. The impact of genotype was assessed by predicting maintenance doses with prior parameter values known to be altered by genetic variability (eg, EC50 for VKORC1 genotype). The prior population was evaluated by fitting the published kinetic-pharmacodynamic model, which underpins the Bayesian tool, to the observed data using NONMEM and comparing the model parameter estimates with published values. The Bayesian tool produced positively biased dose predictions in the new cohort of patients (mean prediction error [95% confidence interval]; 0.32 mg/d [0.14-0.5]). The bias was only observed in patients requiring ≥7 mg/d. The direction and magnitude of the observed bias was not influenced by genotype. The prior model provided a good fit to our data, which suggests that the bias was not caused by different prior and posterior populations. Maintenance doses for patients requiring ≥7 mg/d were overpredicted. The bias was not due to the influence of genotype nor was it related to differences between the prior and posterior populations. There is a need for a more mechanistic model that captures warfarin dose-response relationship at higher warfarin doses.

  14. Good quality of oral anticoagulation treatment in general practice using international normalised ratio point of care testing

    DEFF Research Database (Denmark)

    Løkkegaard, Thomas; Pedersen, Tina Heidi; Lind, Bent

    2015-01-01

    INTRODUCTION: Oral anticoagulation treatment (OACT) with warfarin is common in general practice. Increasingly, international normalised ratio (INR) point of care testing (POCT) is being used to manage patients. The aim of this study was to describe and analyse the quality of OACT with warfarin...... in general practice in the Capital Region of Denmark using INR POCT. METHODS: A total of 20 general practices, ten single-handed and ten group practices using INR POCT, were randomly selected to participate in the study. Practice organisation and patient characteristics were recorded. INR measurements were...... collected retrospectively for a period of six months. For each patient, time in therapeutic range (TTR) was calculated and correlated with practice and patient characteristics using multilevel linear regression models. RESULTS: We identified 447 patients in warfarin treatment in the 20 practices using POCT...

  15. Hemorrhagic stroke and oral anticoagulants: What is to be done?

    Directory of Open Access Journals (Sweden)

    M. A. Domashenko

    2016-01-01

    Full Text Available Hemorrhagic stroke (HS is associated with high mortality and disability rates. Due to the introduction of the current guidelines for the prevention of systemic thromboembolic events in patients with atrial fibrillations and to an increase in the number of older patients, there has been a rise in the incidence of intracranial hemorrhage (ICH associated with the use of oral anticoagulants. The paper discusses medical treatment in patients with HS during therapy with vitamin K antagonists (warfarin and novel oral anticoagulants (dabigatran. rivaroxaban, apixaban, as well as an anticoagulant resumption policy after prior ICH in patients at high risk for thromboembolic events.

  16. Varfarina e femprocumona: experiência de um ambulatório de anticoagulação Warfarina y femprocumona: experiencia de una unidad de anticoagulación Warfarin and phenprocoumon: experience of an outpatient anticoagulation clinic

    Directory of Open Access Journals (Sweden)

    Tiago Luiz Luz Leiria

    2010-01-01

    Full Text Available FUNDAMENTO: Os anticoagulantes orais são amplamente utilizados na cardiologia. Contudo, uma avaliação sobre o seu uso na prática clínica ainda é necessária. OBJETIVOS: Descrever as diferenças na manutenção do controle da anticoagulação, bem como a incidência de eventos hemorrágicos e tromboembólicos entre os usuários de varfarina e femprocumona. MÉTODOS: Estudo de coorte não concorrente de 127 pacientes em uso de anticoagulação oral. RESULTADOS: A femprocumona foi o anticoagulante mais utilizado em 60% dos pacientes. A prevalência de INRFUNDAMENTO: Los anticoagulantes orales son ampliamente utilizados en la cardiología. Con todo, una evaluación acerca de su utilización en la práctica clínica es necesaria todavía. OBJETIVO: Describir las diferencias en el mantenimiento del control de la anticoagulación, así como la incidencia de eventos hemorrágicos y tromboembólicos entre sus usuarios de warfarina y femprocumona. MÉTODOS: Estudio de cohorte no concurrente de 127 pacientes en tratamiento con anticoagulación oral. RESULTADOS: La femprocumona fue el anticoagulante más utilizado en el 60% de los pacientes. La prevalencia de INRBACKGROUND: Oral anticoagulants are broadly used in cardiology. However, it is still necessary to evaluate their use in clinical practice. OBJECTIVES: To describe the differences in the maintenance of anticoagulation control, as well as the incidence of hemorrhagic and thromboembolic events among users of warfarin and phenprocoumon. METHODS: Non-concurrent cohort study of 127 patients using oral anticoagulation. RESULTS: Phenprocoumon was the most frequently used anticoagulant in 60% of the patients. The prevalence of RNI<2 at the last medical appointment was higher among warfarin users (46% vs. 19.5%; p<0.001. During the follow-up, Phenprocoumon users were within the therapeutic range during 60.7% of the period, in comparison with 45.6% of warfarin users (OR:1.84; 95%CI:1.59-2.13; P<0

  17. Oral Health

    Science.gov (United States)

    ... section Home A-Z Health Topics Oral health Oral health > A-Z Health Topics Oral health (PDF, 154 ... To receive Publications email updates Enter email Submit Oral health Women have unique oral health concerns. Changing hormone ...

  18. Influence of fatty acids on the binding of warfarin and phenprocoumon to human serum albumin with relation to anticoagulant therapy

    DEFF Research Database (Denmark)

    Vorum, H; Honoré, B

    1996-01-01

    Warfarin and phenprocoumon binding to human serum albumin was studied by equilibrium dialysis. The first stoichiometric binding constant was 1.89 x 10(5) M-1 for warfarin and 2.40 x 10(5) M-1 for phenprocoumon. The affinity of warfarin was markedly increased on addition of up to 3 mol mol-1 albumin...... coupling of 0.3 kJ mol-1. Six consecutive serum samples were obtained from each of 14 patients undergoing surgery. The serum affinity of the drugs varied considerably corresponding to free drug concentrations between 0.7 and 2.7% for warfarin and between 0.8 and 4.9% for phenprocoumon. The affinity...

  19. Facilitating pharmacogenetic studies using electronic health records and natural-language processing: a case study of warfarin.

    Science.gov (United States)

    Xu, Hua; Jiang, Min; Oetjens, Matt; Bowton, Erica A; Ramirez, Andrea H; Jeff, Janina M; Basford, Melissa A; Pulley, Jill M; Cowan, James D; Wang, Xiaoming; Ritchie, Marylyn D; Masys, Daniel R; Roden, Dan M; Crawford, Dana C; Denny, Joshua C

    2011-01-01

    DNA biobanks linked to comprehensive electronic health records systems are potentially powerful resources for pharmacogenetic studies. This study sought to develop natural-language-processing algorithms to extract drug-dose information from clinical text, and to assess the capabilities of such tools to automate the data-extraction process for pharmacogenetic studies. A manually validated warfarin pharmacogenetic study identified a cohort of 1125 patients with a stable warfarin dose, in which 776 patients were managed by Coumadin Clinic physicians, and the remaining 349 patients were managed by their providers. The authors developed two algorithms to extract weekly warfarin doses from both data sets: a regular expression-based program for semistructured Coumadin Clinic notes; and an advanced weekly dose calculator based on an existing medication information extraction system (MedEx) for narrative providers' notes. The authors then conducted an association analysis between an automatically extracted stable weekly dose of warfarin and four genetic variants of VKORC1 and CYP2C9 genes. The performance of the weekly dose-extraction program was evaluated by comparing it with a gold standard containing manually curated weekly doses. Precision, recall, F-measure, and overall accuracy were reported. Associations between known variants in VKORC1 and CYP2C9 and warfarin stable weekly dose were performed with linear regression adjusted for age, gender, and body mass index. The authors' evaluation showed that the MedEx-based system could determine patients' warfarin weekly doses with 99.7% recall, 90.8% precision, and 93.8% accuracy. Using the automatically extracted weekly doses of warfarin, the authors successfully replicated the previous known associations between warfarin stable dose and genetic variants in VKORC1 and CYP2C9.

  20. Cervical spine abnormalities and instability with myelopathy in warfarin-related chondrodysplasia: 17-year follow-up

    International Nuclear Information System (INIS)

    Takano, Hideyuki; Smith, W.L.; Sato, Yutaka; Kao, S.C.S.

    1998-01-01

    A patient with warfarin embryopathy developed progressive cervical spinal myelopathy owing to bony cervical spinal damage. While there are several descriptions of warfarin embryopathy, the long-term complication of cervical spinal instability has not been reported. This cervical instability may, as in our patient, cause severe neurological dysfunction or even sudden death; therefore, it is important that pediatric radiologists should be alert to this condition. (orig.)

  1. Warfarin anticoagulation in hemodialysis patients with atrial fibrillation: comparison of nephrologist-led and anticoagulation clinic-led management.

    Science.gov (United States)

    Bahbahani, Hamad; AlTurki, Ahmed; Dawas, Ahmed; Lipman, Mark L

    2018-01-08

    There is conflicting evidence of benefit versus harm for warfarin anticoagulation in hemodialysis patients with atrial fibrillation. This equipoise may be explained by suboptimal Time in Therapeutic Range (TTR), which correlates well with thromboembolic and bleeding complications. This study aimed to compare nephrologist-led management of warfarin therapy versus that led by specialized anticoagulation clinic. In a retrospective cohort of chronic hemodialysis patients from two institutions (Institution A: Nephrologist-led warfarin management, Institution B: Anticoagulation clinic-led warfarin management), we identified patients with atrial fibrillation who were receiving warfarin for thromboembolic prophylaxis. Mean TTRs, proportion of patients achieving TTR ≥ 60%, and frequency of INR testing were compared using a logistic regression model. In Institution A, 16.7% of hemodialysis patients had atrial fibrillation, of whom 36.8% were on warfarin. In Institution B, 18% of hemodialysis patients had atrial fibrillation, and 55.5% were on warfarin. The mean TTR was 61.8% (SD 14.5) in Institution A, and 60.5% (SD 15.8) in Institution B (p-value 0.95). However, the proportion of patients achieving TTR ≥ 60% was 65% versus 43.3% (Adjusted OR 2.22, CI 0.65-7.63) and mean frequency of INR testing was every 6 days versus every 13.9 days in Institutions A and B respectively. There was no statistical difference in mean TTR between nephrologist-led management of warfarin and that of clinic-led management. However, the former achieved a trend toward a higher proportion of patients with optimal TTR. This improved therapeutic results was associated with more frequent INR monitoring.

  2. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study

    OpenAIRE

    Perera, Minoli A; Cavallari, Larisa H; Limdi, Nita A; Gamazon, Eric R; Konkashbaev, Anuar; Daneshjou, Roxana; Pluzhnikov, Anna; Crawford, Dana C; Wang, Jelai; Liu, Nianjun; Tatonetti, Nicholas; Bourgeois, Stephane; Takahashi, Harumi; Bradford, Yukiko; Burkley, Benjamin M

    2013-01-01

    Summary BackgroundVKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. MethodsWe did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfar...

  3. Efficacy and Safety of Rivaroxaban Versus Warfarin in Patients Taking Nondihydropyridine Calcium Channel Blockers for Atrial Fibrillation (from the ROCKET AF Trial).

    Science.gov (United States)

    Washam, Jeffrey B; Hellkamp, Anne S; Lokhnygina, Yuliya; Piccini, Jonathan P; Berkowitz, Scott D; Nessel, Christopher C; Becker, Richard C; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Singer, Daniel E; Patel, Manesh R

    2017-08-15

    Non-dihydropyridine calcium channel blockers (non-DHP CCBs) possess combined P-glycoprotein and moderate CYP3A4 inhibition, which may lead to increased exposure of medications that are substrates for these metabolic pathways, such as rivaroxaban. We evaluated the use and outcomes of non-DHP CCBs in patients with atrial fibrillation (AF) in Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF). We assessed clinical outcomes in patients who received non-DHP CCBs and the impact on the efficacy and safety of rivaroxaban compared with warfarin. Stroke or noncentral nervous system (CNS) systemic embolism (SE), major or nonmajor clinically relevant (NMCR) bleeding, all-cause death, and major bleeding were compared according to non-DHP CCB use. At randomization, 1,308 patients (9.2%) were taking a non-DHP CCB. They were more likely to be women, have diabetes and COPD, and less likely to have heart failure and had a lower mean CHADS 2 score (3.3 vs 3.5). Non-DHP CCB use was not associated with an increased risk of stroke/non-CNS SE (p = 0.11) or the composite outcome of NMCR or major bleeding (p = 0.087). Non-DHP CCB use was associated with an increased risk of major bleeding (adjusted hazard ratio 1.50, 95% CI 1.11 to 2.04) and intracranial hemorrhage (adjusted hazard ratio 2.84, 95% CI 1.53 to 5.29). No significant difference was observed in the primary efficacy (stroke or non-CNS SE; adjusted interaction p value = 0.38) or safety outcome (NMCR or major bleeding; adjusted interaction p value = 0.14) between rivaroxaban and warfarin with non-DHP CCB use. In conclusion, although the overall use of non-DHP CCBs was associated with an increased risk of major bleeding and intracranial hemorrhage, the use was not associated with a significant change in the safety or efficacy of rivaroxaban compared with warfarin observed in ROCKET AF. Copyright © 2017

  4. Rivaroxaban limits complement activation compared with warfarin in antiphospholipid syndrome patients with venous thromboembolism.

    Science.gov (United States)

    Arachchillage, D R J; Mackie, I J; Efthymiou, M; Chitolie, A; Hunt, B J; Isenberg, D A; Khamashta, M; Machin, S J; Cohen, H

    2016-11-01

    Essentials Complement activation has a pathogenic role in thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Complement activation markers were elevated in anticoagulated thrombotic APS patients. Complement activation decreased in APS patients switching from warfarin to rivaroxaban. Background Complement activation may play a major role in the pathogenesis of thrombotic antiphospholipid syndrome (APS). Coagulation proteases such as factor Xa can activate complement proteins. Aims To establish whether rivaroxaban, a direct factor Xa inhibitor, limits complement activation compared with warfarin in APS patients with previous venous thromboembolism (VTE). Methods A total of 111 APS patients with previous VTE, on warfarin target INR 2.5, had blood samples taken at baseline and at day 42 after randomization in the RAPS (Rivaroxaban in Antiphospholipid Syndrome) trial. Fifty-six patients remained on warfarin and 55 switched to rivaroxaban. Fifty-five normal controls (NC) were also studied. Markers of complement activation (C3a, C5a, terminal complement complex [SC5b-9] and Bb fragment) were assessed. Results APS patients had significantly higher complement activation markers compared with NC at both time-points irrespective of the anticoagulant. There were no differences between the two patient groups at baseline, or patients remaining on warfarin at day 42. In 55 patients randomized to rivaroxaban, C3a, C5a and SC5b-9 were lower at day 42 (median (ng mL -1 ) [confidence interval] 64 [29-125] vs. 83 [35-147], 9 [2-15] vs. 12 [4-18] and 171 [56-245] vs. 201 [66-350], respectively) but levels of Bb fragment were unchanged. There were no correlations between rivaroxaban levels and complement activation markers. Conclusions APS patients with previous VTE on warfarin exhibit increased complement activation, which is likely to occur via the classical pathway and is decreased by rivaroxaban administration

  5. Dabigatran versus warfarin after bioprosthesis valve replacement for the management of atrial fibrillation postoperatively: protocol.

    Science.gov (United States)

    Duraes, Andre Rodrigues; Roriz, Pollianna Ds; Bulhoes, Fabio V; Nunes, Bianca DA; Muniz, Juliana Qv; Neto, Italvar Ndcr; Fernandes, Andre Ms; Reis, Francisco Jfbd; Camara, Edmundo Jn; Junior, Erenaldo Dsr; Segundo, Deusdeth Ts; Silva, Felipe Pinho E Albuquerque; Aras, Roque

    2014-04-01

    Warfarin and similar vitamin K antagonists have been the standard therapy for patients with mechanical or biological valve prosthesis and atrial fibrillation (AF). Even with the appropriate use of therapy, some studies have reported that there is a high incidence of thromboembolic events, 1%-4% per year. Furthermore, a bleeding risk is significant, ranging from 2% to 9% per year, according to some studies. The objective of our study was to examine the effect of dabigatran etexilate versus dose-adjusted warfarin for the prevention of intracardiac thrombus in persistent or permanent AF at least 3 months after aortic and/or mitral bioprosthesis replacement. Dabigatran versus warfarin after bioprosthesis valve replacement for the management of atrial fibrillation postoperatively (DAWA) is a phase 2, prospective, open label, randomized exploratory pilot study. The main variable to be observed in this study is intracardiac thrombus. From August 2013 to April 2015, 100 patients, at least 3 months after aortic and/or mitral bioprosthesis replacement and permanent or persistent AF postoperatively, who match eligibility criteria will be selected from Ana Nery Hospital in Salvador-Bahia with a follow-up of three months. Patients were randomly assigned in a 1:1 ratio to receive either dabigatran etexilate or warfarin. Although the present study has no statistic power to proof non-inferiority, it is expected that the dabigatran etexilate group will be protected as well as the warfarin group from intracardiac thrombus, without increasing the bleeding rates, since we are using safer doses (110 mg bid). The lack of necessity of monitoring INR is also another factor that contributes to a better adherence to the new drug and it can make all the difference in the manner of doing anticoagulation for patients with similar clinical characteristics. The study is in the recruitment phase. It is possible that dabigatran etexilate is as effective as warfarin in preventing the emergence of

  6. Warfarin Anticoagulation Therapy in Caribbean Hispanics of Puerto Rico: A Candidate Gene Association Study

    Directory of Open Access Journals (Sweden)

    Karla Claudio-Campos

    2017-06-01

    Full Text Available Existing algorithms account for ~50% of observed variance in warfarin dose requirements after including common polymorphisms. However, they do not perform as well in populations other than Caucasians, in part because some ethno-specific genetic variants are overlooked. The objective of the present study was to identify genetic polymorphisms that can explain variability in warfarin dose requirements among Caribbean Hispanics of Puerto Rico. Next-Generation Sequencing of candidate genes CYP2C9 and VKORC1 and genotyping by DMET® Plus Assay of cardiovascular patients were performed. We also aimed at characterizing the genomic structure and admixture pattern of this study cohort. Our study used the Extreme Discordant Phenotype approach to perform a case-control association analysis. The CYP2C9 variant rs2860905, which was found in all the major haplotypes occurring in the Puerto Rican population, showed stronger association with warfarin sensitivity (<4 mg/day than common variants CYP2C9*2 and CYP2C9*3. Although, CYP2C9*2 and CYP2C9*3 are separately contained within two of the haplotypes, 10 subjects with the sensitive phenotype were carriers of only the CYP2C9 rs2860905 variant. Other polymorphisms in CES2 and ABCB1 were found to be associated with warfarin resistance. Incorporation of rs2860905 in a regression model (R2 = 0.63, MSE = 0.37 that also includes additional genetics (i.e., VKORC1-1639 G>A; CYP2C9 rs1856908; ABCB1 c.IVS9-44A>G/ rs10276036; CES2 c.269-965A>G/ rs4783745 and non-genetic factors (i.e., hypertension, diabetes and age showed better prediction of warfarin dose requirements than CYP2C9*2 and CYP2C9*3 combined (partial R2 = 0.132 vs. 0.023 and 0.007, respectively, p < 0.001. The genetic background of Puerto Ricans in the study cohort showed a tri-hybrid admixture pattern, with a slightly higher than expected contribution of Native American ancestry (25%. The genomic diversity of Puerto Ricans is highlighted by the presence of

  7. Low warfarin resistance frequency in Norway rats in two cities in China after 30 years usage of anticoagulant rodenticides.

    Science.gov (United States)

    Ma, Xiaohui; Wang, Da-Wei; Li, Ning; Liu, Lan; Tian, Lin; Luo, Chan; Cong, Lin; Feng, Zhiyong; Liu, Xiao-Hui; Song, Ying

    2018-04-17

    Anticoagulant rodenticides have been widely used in rodent control in China for over 30 years and resistant Norway rats have been reported. Mutations in the vitamin K epoxide reductase complex, subunit 1 (Vkorc1) gene can cause anticoagulant resistance in rodents. In this study, we analyzed the Vkorc1 polymorphisms of 681 Norway rats collected in Zhanjiang and Harbin City in China from 2008 to 2015 and evaluated the warfarin resistance frequency. Analysis revealed 4 mutations including 3 not previously reported. Two new synonymous mutations His68His and Leu105Leu are not associated with warfarin resistance. One new nonsynonymous mutation Ala140Thr was found in Zhanjiang rat samples collected in 3 years with low frequencies (3.3%-4.0%) and is likely associated with warfarin resistance. Laboratory resistance tests suggested low warfarin resistance frequencies in rats from Zhanjiang (4.9%-17.1%) and Harbin City (0-2.5%). Both genetic analysis and laboratory resistance tests suggested low warfarin resistance frequencies in rats from Zhanjiang and Harbin City. The alternative usage of FGARs and SGARs might represent an effective strategy against the development of warfarin resistance in Norway rats in China. This article is protected by copyright. All rights reserved.

  8. Fate of [14C] warfarin in guinea-pigs: effect of a concomitant single dose of salicylate

    International Nuclear Information System (INIS)

    Wong, L.T.; Solomonraj, G.; Thomas, B.H.

    1978-01-01

    When a single dose of sodium salicylate (177.8 mg kg -1 , by mouth) was given with [ 14 C] warfarin (1 mg kg -1 , i.p.) to guinea-pigs, the salicylate depressed the blood concentrations of 14 C for 6 h. At 1 h, salicylate increased the distribution of 14 C in the liver and brain, but at 1 and 6 h it was decreased in the blood and kidney. A significant portion of the 14 C was excreted into the bile, but was subject to enterohepatic circulation and then excreted by the kidney. There was an enhancement of the biliary elimination of 14 C in the first 5 h after salicylate and a decrease in 14 C concentration in blood; the proportion of warfarin to its metabolites excreted in the urine and bile was unchanged. Salicylate displaced serum protein bound [ 14 C] warfarin in vitro. Salicylate increases the initial biliary elimination of warfarin by displacing some of that bound to plasma protein. This facilitated uptake of warfarin by the liver where it was metabolized. This effect of salicylate did not modify the hypoprothrombinaemia produced by warfarin. (author)

  9. Rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation – the J-ROCKET AF study –.

    Science.gov (United States)

    Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

    2012-01-01

    The global ROCKET AF study evaluated once-daily rivaroxaban vs. warfarin for stroke and systemic embolism prevention in patients with atrial fibrillation (AF). A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial. Patients (n=1,280) with non-valvular AF at increased risk for stroke were randomized to receive 15 mg once-daily rivaroxaban or warfarin dose-adjusted according to Japanese guidelines. The primary objective was to determine non-inferiority of rivaroxaban against warfarin for the principal safety outcome of major and non-major clinically relevant bleeding, in the on-treatment safety population. The primary efficacy endpoint was the composite of stroke and systemic embolism. Non-inferiority of rivaroxaban to warfarin was confirmed; the rate of the principal safety outcome was 18.04% per year in rivaroxaban-treated patients and 16.42% per year in warfarin-treated patients (hazard ratio [HR] 1.11; 95% confidence interval 0.87-1.42; PROCKET AF demonstrated the safety of a Japan-specific rivaroxaban dose and supports bridging the global ROCKET AF results into Japanese clinical practice.

  10. Warfarin and acetaminophen interaction: a summary of the evidence and biologic plausibility.

    Science.gov (United States)

    Lopes, Renato D; Horowitz, John D; Garcia, David A; Crowther, Mark A; Hylek, Elaine M

    2011-12-08

    Ms TS is a 66-year-old woman who receives warfarin for prevention of systemic embolization in the setting of hypertension, diabetes, and atrial fibrillation. She had a transient ischemic attack about 4 years ago when she was receiving aspirin. Her INR control was excellent; however, over the past few months it has become erratic, and her average dose required to maintain an INR of 2.0 to 3.0 appears to have decreased. She has had back pain over this same period and has been taking acetaminophen at doses at large as 650 mg four times daily, with her dose varying based on her symptoms. You recall a potential interaction and wonder if (1) her acetaminophen use is contributing to her loss of INR control, and (2) does this interaction place her at increased risk of warfarin-related complications?

  11. Development and validation of a dissolution method for warfarin sodium and aspirin combination tablets.

    Science.gov (United States)

    McCormick, T J; Gibson, A B; Diana, F J

    1997-08-01

    A dissolution method for warfarin sodium-aspirin combination tablets was developed which utilizes USP Apparatus 1 (baskets) at 50 rpm with 900 ml of phosphate buffer (pH 6.8; 0.05 M) medium at 37 degrees C. A reversed-phase liquid chromatographic method was also developed for the simultaneous determination of warfarin sodium, aspirin and salicylic acid on an octadecylsilica column using acetonitrile-tetrahydrofuran-glacial acetic acid-water (23:5:5:67, v/v/v/v) as the mobile phase with UV detection at 282 nm. Validation data were obtained which demonstrate that the dissolution methodology is accurate, precise, linear and rugged for the combination tablets.

  12. Outcomes With Edoxaban Versus Warfarin in Patients With Previous Cerebrovascular Events

    DEFF Research Database (Denmark)

    Rost, Natalia S; Giugliano, Robert P; Ruff, Christian T

    2016-01-01

    without previous IS/TIA, patients with previous IS/TIA were at higher risk of both thromboembolism and bleeding (stroke/systemic embolic events 2.83% versus 1.42% per year; Phemorrhage, 0.70% versus 0.40% per year; P... patients with previous IS/TIA, annualized intracranial hemorrhage rates were lower with HDER than with warfarin (0.62% versus 1.09%; absolute risk difference, 47 [8-85] per 10 000 patient-years; hazard ratio, 0.57; 95% confidence interval, 0.36-0.92; P=0.02). No treatment subgroup interactions were found......BACKGROUND AND PURPOSE: Patients with atrial fibrillation and previous ischemic stroke (IS)/transient ischemic attack (TIA) are at high risk of recurrent cerebrovascular events despite anticoagulation. In this prespecified subgroup analysis, we compared warfarin with edoxaban in patients...

  13. A systematic review of the pharmacokinetic and pharmacodynamic interactions of herbal medicine with warfarin.

    Directory of Open Access Journals (Sweden)

    Songie Choi

    Full Text Available The aim of this study was to systematically review data regarding pharmacokinetic (PK-pharmacodynamic (PD parameters from randomized controlled trials relating to interactions between herbal medicines and warfarin.Three electronic databases were searched to identify relevant trials. Two reviewers independently performed the study selection and data extraction. The risk of bias and reporting quality were also assessed independently by two reviewers using the Cochrane risk of bias tool and the consolidated standards of reporting trials (CONSORT. Outcomes were measured for all reported PK-PD parameters and adverse events.Nine randomized controlled trials met our inclusion criteria. Most of the included studies were unclear regarding the risk of bias and had a low quality of methodology. Using CONSORT, the reporting percentages for the articles ranged from 36.5% to 61.5% and the mean percentage for all articles was 45.6%. St John's wort and echinacea affected the PK parameters of warfarin. Ginseng, ginger, garlic, and cranberry had no significant effect on the PK parameters. American ginseng altered the PD parameters of warfarin. St John's wort, ginseng, Korea red ginseng, ginkgo, ginger, garlic, aged garlic, and echincea did not significantly alter the PD parameters. Studies of ginkgo and cranberry showed conflicting results on the PK parameters and PD parameters, respectively. The incidence of adverse events in all trials was low and no major adverse events were reported.It was difficult to determine whether ten herbal medicines had significant effects on the PK-PD parameters of warfarin. Low quality of evidence, different compounds within and different compositions of the herbs, and methodological limitations of the crossover study, which is a clinical study in which subjects receive a sequence of different interventions, made it difficult to form conclusions. Additional studies that remedy these vulnerabilities are necessary to verify these

  14. Dabigatran Versus Warfarin After Bioprosthesis Valve Replacement for the Management of Atrial Fibrillation Postoperatively: Protocol

    OpenAIRE

    Duraes, Andre Rodrigues; Roriz, Pollianna DS; Bulhoes, Fabio V; Nunes, Bianca DA; Muniz, Juliana QV; Neto, Italvar NDCR; Fernandes, Andre MS; Reis, Francisco JFBD; Camara, Edmundo JN; Junior, Erenaldo DSR; Segundo, Deusdeth TS; Silva, Felipe Pinho E Albuquerque; Aras, Roque

    2014-01-01

    Background Warfarin and similar vitamin K antagonists have been the standard therapy for patients with mechanical or biological valve prosthesis and atrial fibrillation (AF). Even with the appropriate use of therapy, some studies have reported that there is a high incidence of thromboembolic events, 1%-4% per year. Furthermore, a bleeding risk is significant, ranging from 2% to 9% per year, according to some studies. Objective The objective of our study was to examine the effect of dabigatran...

  15. Treatments for Reversing Warfarin Anticoagulation in Patients with Acute Intracranial Hemorrhage: A Structured Literature Review

    Science.gov (United States)

    2011-07-08

    rapid INR normalization and decreased intracranial hematoma expansion [36-40]. The medical literature’s reporting of these reversal agents’ impact on... intracranial haemorrhages. Scott Med J 2000, 45:105-109. 42. Huttner HB, Schellinger PD, Hartmann M, et al. Hematoma growth and outcome in...available soon. Treatments for reversing warfarin anticoagulation in patients with acute intracranial hemorrhage: a structured literature review

  16. A review of a priori regression models for warfarin maintenance dose prediction.

    Directory of Open Access Journals (Sweden)

    Ben Francis

    Full Text Available A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.

  17. A review of a priori regression models for warfarin maintenance dose prediction.

    Science.gov (United States)

    Francis, Ben; Lane, Steven; Pirmohamed, Munir; Jorgensen, Andrea

    2014-01-01

    A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.

  18. Clinical factors influencing normalization of prothrombin time after stopping warfarin: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Zondag Michelle

    2008-10-01

    Full Text Available Abstract Background Anticoagulation with warfarin should be stopped 4–6 days before invasive procedures to avoid bleeding complications. Despite this routine, some patients still have high International Normalized Ratio (INR values on the day of surgery and the procedure may be cancelled. We sought to identify easily available clinical characteristics that may influence the rate of normalization of prothrombin time when warfarin is stopped before surgery or invasive procedures. Methods Clinical data were collected retrospectively from consecutive cases from two cohorts, who stopped warfarin 6 days before surgery. An INR value of 1.6 or higher on the day of surgery or requirement for reversal with vitamin K the day before surgery were criteria for slow return (S to normal INR. Results Of 202 patients, 14 (7% were classified as S. Eight of the S-patients required reversal with vitamin K one day before surgery and in another case surgery was cancelled due to high INR. Baseline INR was the only variable significantly associated with classification as S in stepwise logistic regression analysis (p = 0.003. The odds ratio for being in the normal group was 0.27 (95% confidence interval 0.12–0.62 for each unit baseline INR increased. The positive predictive value of baseline INR with a cut off at > 3.0 was only 15% and for INR > 3.5 it was 33%. Conclusion Baseline INR, but not the size of the maintenance dose, is associated with the rate of normalization of prothrombin time after stopping warfarin, but it has limited utility as predictor in clinical practice. Whenever normal hemostasis is considered crucial for the safety, the INR should be checked again before the invasive procedure.

  19. Assessment of patient perceptions concerning a community pharmacy-based warfarin monitoring service

    Directory of Open Access Journals (Sweden)

    Stefanie Ferreri, PharmD, CDE, BCACP, FAPhA1

    2012-01-01

    Full Text Available Objective: To assess patient perceptions of a North Carolina community pharmacy-based warfarin monitoring service. Methods: Prospective study of patients 18 years of age and older, who filled a prescription for warfarin, in one of five Raleigh area community pharmacies, between May 1, 2010 and October 31, 2010. A 14 item survey, along with a self-addressed stamped envelope, was mailed to 330 identified patients. The survey inquired about details of current anticoagulation monitoring services, interest in utilizing a local community pharmacy for this service, and confidence in a pharmacist-managed program. Results: 26% of surveys were returned. 48% of surveyed individuals responded that they would be interested in having their warfarin monitoring performed by a trained pharmacist in a community pharmacy setting. Conclusion: Many participants responded that the community pharmacy would be more convenient than or as convenient as their current location. This may be a new clinical service that could be offered in certain community pharmacies.

  20. Assessment of patient perceptions concerning a community pharmacy-based warfarin monitoring service

    Directory of Open Access Journals (Sweden)

    Jennifer Waitzman

    2012-01-01

    Full Text Available Objective: To assess patient perceptions of a North Carolina community pharmacy-based warfarin monitoring service. Methods: Prospective study of patients 18 years of age and older, who filled a prescription for warfarin, in one of five Raleigh area community pharmacies, between May 1, 2010 and October 31, 2010. A 14 item survey, along with a self-addressed stamped envelope, was mailed to 330 identified patients. The survey inquired about details of current anticoagulation monitoring services, interest in utilizing a local community pharmacy for this service, and confidence in a pharmacist-managed program. Results: 26% of surveys were returned. 48% of surveyed individuals responded that they would be interested in having their warfarin monitoring performed by a trained pharmacist in a community pharmacy setting. Conclusion: Many participants responded that the community pharmacy would be more convenient than or as convenient as their current location. This may be a new clinical service that could be offered in certain community pharmacies.   Type: Original Research

  1. Improvement of adequate use of warfarin for the elderly using decision tree-based approaches.

    Science.gov (United States)

    Liu, K E; Lo, C-L; Hu, Y-H

    2014-01-01

    Due to the narrow therapeutic range and high drug-to-drug interactions (DDIs), improving the adequate use of warfarin for the elderly is crucial in clinical practice. This study examines whether the effectiveness of using warfarin among elderly inpatients can be improved when machine learning techniques and data from the laboratory information system are incorporated. Having employed 288 validated clinical cases in the DDI group and 89 cases in the non-DDI group, we evaluate the prediction performance of seven classification techniques, with and without an Adaptive Boosting (AdaBoost) algorithm. Measures including accuracy, sensitivity, specificity and area under the curve are used to evaluate model performance. Decision tree-based classifiers outperform other investigated classifiers in all evaluation measures. The classifiers supplemented with AdaBoost can generally improve the performance. In addition, weight, congestive heart failure, and gender are among the top three critical variables affecting prediction accuracy for the non-DDI group, while age, ALT, and warfarin doses are the most influential factors for the DDI group. Medical decision support systems incorporating decision tree-based approaches improve predicting performance and thus may serve as a supplementary tool in clinical practice. Information from laboratory tests and inpatients' history should not be ignored because related variables are shown to be decisive in our prediction models, especially when the DDIs exist.

  2. Sudden Death by Spontaneous Epiglottic Hematoma Secondary to High Blood Levels of Warfarin.

    Science.gov (United States)

    Gilard-Pioc, Séverine; Guerard, Pascal; Paraf, François; François-Purssell, Irène

    2017-07-01

    A 67-year-old man was found dead, at his home. On external examination, we found a voluminous purplish black ecchymosis of the anterior neck area. On internal examination, we found a voluminous epiglottis hematoma completely obstructing the upper airway. It was associated with other sites of intra-abdominal hemorrhage. Toxicological studies revealed the presence of warfarin at a concentration of 8.4 mg/L in peripheral blood, which supposes an INR well above 4.5. To conclude, we supposed death was due to asphyxia secondary to a spontaneous epiglottic hematoma caused by a high blood concentration of warfarin. Hemorrhage in the epiglottis is very rare. To our knowledge, our patient is the only case of "sudden death" reported with spontaneous epiglottic hematoma due to high blood concentration of warfarin. In forensic practice, an anterior neck ecchymosis, without trauma, may suggest hemorrhage into soft airway tissues. Pathology findings make it possible to exclude exogenous trauma. © 2017 American Academy of Forensic Sciences.

  3. Prescription Patterns of Non-Vitamin K Oral Anticoagulants Across Indications and Factors Associated with Their Increased Prescribing in Atrial Fibrillation Between 2012-2015: A Study from the Norwegian Prescription Database.

    Science.gov (United States)

    Urbaniak, Anna Maria; Strøm, Bjørn Oddvar; Krontveit, Randi; Svanqvist, Kristin Helene

    2017-08-01

    We studied prescription patterns for non-vitamin K oral anticoagulants (NOACs) in Norway between 2012 and 2015, and compared NOAC and warfarin patient characteristics such as age, gender and cardiovascular (CV) co-medications across reimbursed indications. Factors associated with NOAC prescribing in atrial fibrillation (AF) were also analysed. All Norwegian patients (N = 156,124) who received at least one dispensed NOAC or warfarin prescription within the indications of AF, deep vein thrombosis and pulmonary embolism (DVT_PE) or prevention of venous thromboembolic events after a hip or knee surgery (VTE_surg) between 2012 and 2015 were included in the study. Descriptive statistics was applied to compare patient characteristics between NOACs and warfarin across indications and a logistic regression model was used to identify factors associated with NOAC prescribing in AF. NOACs and warfarin were most commonly prescribed in AF (83,729 patients in 2015), followed by DVT_PE (16,077 patients) and lastly in VTE_surg (4060 patients). In 2015, NOACs achieved a dominant (>50%) patient share over warfarin in AF and DVT_PE, and were prescribed in >80% of new oral anticoagulation (OAC) patients. Apixaban, despite its delayed market entry, emerged as the preferred NOAC in VTE_surg (46% share), whereas rivaroxaban captured a 43% patient share in DVT_PE. Warfarin patients were on average older and received more CV co-medication than NOAC patients in AF and DVT_PE. Age, gender and certain CV co-medications emerged as significant predictors of NOAC prescribing in AF. AF patients 74 years old (OR 0.51-0.77). Women had 32% higher odds of receiving a NOAC in AF. NOACs achieved a dominant market share over warfarin within 3 years from receiving reimbursement in Norway. There were significant differences in patient characteristics between drugs and indications.

  4. Direct oral anticoagulants: analysis of worldwide use and popularity using Google Trends.

    Science.gov (United States)

    Lippi, Giuseppe; Mattiuzzi, Camilla; Cervellin, Gianfranco; Favaloro, Emmanuel J

    2017-08-01

    Four direct oral anticoagulants (DOACs) have been approved for clinical use by many medicines regulatory agencies around the world. Due to increasing use of these drugs in routine practice, we planned an original study to investigate their worldwide diffusion using a popular Web-search engine. Two electronic searches were performed using Google Trends, the former using the keywords "warfarin" AND "heparin" AND "fondaparinux", and the latter using the keywords "warfarin" AND "dabigatran" AND "rivaroxaban" AND "apixaban" AND "edoxaban", both using the search criterion "prescription drug". No language restriction was applied, and the searches were carried out from the first date available in Google Trends (January 1 st , 2004) to present time (June 1 st , 2017). The median Google Trends score of warfarin (i.e., 86) was consistently higher than that of heparin (54; PGoogle searches for DOACs were performed in North America, central-eastern Europe and Australia. The results of our analysis suggest that the popularity of DOACs is constantly increasing around the world, whereas that of warfarin has exhibited a constant and inexorable decline.

  5. Comparison of hospital length of stay between hospitalized non-valvular atrial fibrillation patients treated with either apixaban or warfarin.

    Science.gov (United States)

    Farr, Amanda M; Jing, Yonghua; Johnston, Stephen; Trocio, Jeffrey; Singhal, Shalabh; Bruno, Amanda; Graham, John

    2015-01-01

    Hospital length of stay (LOS) is an important cost driver for hospitals and payers alike. Hospitalized non-valvular atrial fibrillation (NVAF) patients treated with apixaban may have shorter LOS than those treated with warfarin because of the absence of need for INR monitoring in apixaban. Thus, this study compared hospital LOS between hospitalized NVAF patients treated with either apixaban or warfarin. This was a retrospective, observational cohort study based on a large US database including diagnosis, procedure, and drug administration information from >600 acute-care hospitals. Patients selected for study were aged ≥18 years and had a hospitalization record with an ICD-9-CM diagnosis code for atrial fibrillation (AF) in any position from 1 January 2013 to 28 February 2014 (index hospitalization). Patients with diagnoses indicative of rheumatic mitral valvular heart disease or a valve replacement procedure during index hospitalization were excluded. Patients were required to have been treated with either apixaban or warfarin, and not treated with rivaroxaban or dabigatran, during index hospitalization. Apixaban patients were propensity score (PS) matched to warfarin patients at a 1:1 ratio, using patient demographic/clinical and hospital characteristics. The study outcome was hospital LOS, calculated as discharge date minus admission date; a sensitivity analysis calculated hospital LOS as discharge date minus first anticoagulant administration date. Sub-analyses were conducted among patients with a primary diagnosis of AF. The study included 832 apixaban patients matched to 832 warfarin patients. Mean [standard deviation (SD)] and median hospital LOS were significantly (p < 0.001) shorter in apixaban patients (4.5 [4.2] and 3 days) than in warfarin patients (5.4 [5.0] and 4). Results were consistent in the sensitivity and sub-analyses. Among NVAF patients, apixaban treatment was associated with shorter hospital LOS when compared with warfarin treatment. These

  6. Thrombotic genetic risk factors and warfarin pharmacogenetic variants in São Miguel's healthy population (Azores

    Directory of Open Access Journals (Sweden)

    Pacheco Paula R

    2009-06-01

    Full Text Available Summary Background The Azorean population presents the highest standardized mortality rate for cardiovascular diseases (CVD when compared to mainland Portugal and other populations. Since thrombosis is a common cause of CVD, we assessed four polymorphisms in three thrombotic risk genes – F5 (G1691A, F2 (G20210A and MTHFR (C677T, A1298C, in 469 healthy blood donors from São Miguel Island (Azores. We also analysed the CYP2C9 (C430T, A1075C and VKORC1 (G1639A variants in fifty-eight individuals with predisposition to thrombosis (possessing at least one variation in F5 or F2 genes and one in MTHFR to evaluate their warfarin drug response genetic profiles. Results Among the 469 individuals, the data showed that thrombotic risk allele frequencies – 1691A (4.9%, 20210A (1.8%, 677T (41.7% and 1298C (24.8% – were similar to other Caucasians, but significantly different from mainland Portuguese (χ2, p F5, F2, MTHFR C677T and A1298C. Complete homozygosity for all wild-type alleles (GG GG CC AA was present in 11.7%, being GG GG CT AA (22.4% the most frequent profile. The results also demonstrated that 12.4% (58 out of 469 of São Miguel islanders have increased genetic predisposition to thrombosis. Subsequently, we evaluated these individuals for their warfarin response genetic profiles. The data showed that seven out of fifty-eight individuals are poor metabolizers (two with CYP2C9*2/*2 and five with CYP2C9*2/*3 genotypes. VKORC1 polymorphism analysis identified twelve individuals (20.7% with AA genotype, who probably will require lower doses of warfarin. The joint analysis of CYP2C9 and VKORC1 revealed that 79.3% (46 out of 58 of the individuals carry at least one polymorphism in these genes. Within these, twenty-five individuals (43.1% need intermediate and/or low doses of warfarin, if treatment is started. Conclusion The present study demonstrated, for the first time, that São Miguel, and possibly the Azores population, shows significant

  7. Clinical implications of antiretroviral drug interactions with warfarin: a case-control study.

    Science.gov (United States)

    Esterly, John S; Darin, Kristin M; Gerzenshtein, Lana; Othman, Fidah; Postelnick, Michael J; Scarsi, Kimberly K

    2013-06-01

    Warfarin, a frequently prescribed anticoagulant with a narrow therapeutic index, is susceptible to drug-drug interactions with antiretroviral therapy (ART). This study compared the warfarin maintenance dose (WMD) between patients receiving and not receiving ART and evaluated predictors of warfarin dosage among those on ART. This was a case-control (1:2) study. Cases were HIV-infected patients receiving warfarin and protease inhibitor (PI)- and/or non-nucleoside reverse transcriptase inhibitor (NNRTI)-based ART. Controls were randomly selected HIV-uninfected patients receiving warfarin. The WMD was compared between cases and controls and between cases on varying ART regimens. Bivariate comparisons were performed and a linear regression model was developed to identify predictors of WMD. We identified 18 case and 36 control patients eligible for inclusion. Cases were younger than controls (mean age: 45.8 versus 63.1 years, P African American (50.0% versus 22.2%, P=0.04). ART was classified as PI-based (n=9), NNRTI-based (n=7) and PI + NNRTI-based (n=2). The WMD (mean ± SD) differed between cases and controls (8.6  ±  3.4 mg versus 5.1 ± 1.5 mg, P ART regimens (PI: 8.8  ±  4.5 mg; NNRTI: 8.6   ± 1.8 mg; PI + NNRTI: 7.3  ±  3.3 mg; P = 0.86). Race and ritonavir dose were independent predictors of WMD, predicting an increase of 3.9 mg (95% CI: 0.88-6.98, P = 0.02) if a patient was African American or 3.7 mg (95% CI: 0.53-6.89, P = 0.03) if the total daily ritonavir dose was 200 mg. The required WMD was significantly higher in patients receiving ART. Prompt dose titration to achieve a higher WMD with vigilant monitoring may be required due to these drug-drug interactions.

  8. Venous thromboembolic prophylaxis after simultaneous bilateral total knee arthroplasty: aspirin versus warfarin.

    Science.gov (United States)

    Goel, R; Fleischman, A N; Tan, T; Sterbis, E; Huang, R; Higuera, C; Parvizi, J; Rothman, R H

    2018-01-01

    The aims of this study were to compare the efficacy of two agents, aspirin and warfarin, for the prevention of venous thromboembolism (VTE) after simultaneous bilateral total knee arthroplasty (SBTKA), and to elucidate the risk of VTE conferred by this procedure compared with unilateral TKA (UTKA). A retrospective, multi-institutional study was conducted on 18 951 patients, 3685 who underwent SBTKA and 15 266 who underwent UTKA, using aspirin or warfarin as VTE prophylaxis. Each patient was assigned an individualised baseline VTE risk score based on a system using the Nationwide Inpatient Sample. Symptomatic VTE, including pulmonary embolism (PE) and deep vein thrombosis (DVT), were identified in the first 90 days post-operatively. Statistical analyses were performed with logistic regression accounting for baseline VTE risk. The adjusted incidence of PE following SBTKA was 1.0% (95% confidence interval (CI) 0.86 to 1.2) with aspirin and 2.2% (95% CI 2.0 to 2.4) with warfarin. Similarly, the adjusted incidence of VTE following SBTKA was 1.6% (95% CI 1.1 to 2.3) with aspirin and 2.5% (95% CI 1.9 to 3.3) with warfarin. The risk of PE and VTE were reduced by 66% (odds ratio (OR) 0.44, 95% CI 0.25 to 0.78) and 38% (OR 0.62, 95% CI 0.38 to 1.0), respectively, using aspirin. In addition, the risk of PE was 204% higher for patients undergoing SBTKA relative to those undergoing UTKA. For each ten-point increase in baseline VTE risk, the risk of PE increased by 25.5% for patients undergoing SBTKA compared with 10.5% for those undergoing UTKA. Patients with a history of myocardial infarction or peripheral vascular disease had the greatest increase in risk from undergoing SBTKA instead of UTKA. Aspirin is more effective than warfarin for the prevention of VTE following SBTKA, and serves as the more appropriate agent for VTE prophylaxis for patients in all risk categories. Furthermore, patients undergoing SBTKA are at a substantially increased risk of VTE, even more so for

  9. Retrospective study of rFVIIa, 4-factor PCC, and a rFVIIa and 3-factor PCC combination in improving bleeding outcomes in the warfarin and non-warfarin patient.

    Science.gov (United States)

    DeLoughery, Emma; Avery, Brian; DeLoughery, Thomas G

    2016-07-01

    In case of severe bleeding, the physician must rapidly and effectively halt bleeding without the risk of thromboembolic complications. Despite widespread use, no study has directly compared recombinant activated factor VII (rFVIIa), the rFVIIa and 3-factor prothrombin complex concentrate (PCC) combination ("combination"), and 4-factor PCC on their effectiveness in improving patient outcomes. This study examined the medical records of 299 patients, 65.2% on warfarin prior to admission, who received these hemostatic agents and were admitted to an ICU or through the emergency department at Oregon Health & Science University. Mortality, length of stay, change in international normalized ratio (INR), plasma use, and number of thromboembolic complications were used to assess effectiveness. In patients receiving warfarin, the combination group had the greatest decrease in INR as well as lowest overall INR, but experienced a higher number of clotting complications, while the rFVIIa group used the most plasma. Non-warfarin patients in the combination group had the shortest length of stay among survivors, but the rFVIIa group had the lowest mortality. Based on this data, it may be prudent to further study the use of rFVIIa in treating extreme bleeding in the non-warfarin patient, while this study supports other data that 4-factor PCC may be the most prudent for the warfarin patient. Am. J. Hematol. 91:705-708, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. Potentially avoidable inpatient nights among warfarin receiving patients; an audit of a single university teaching hospital.

    LENUS (Irish Health Repository)

    Forde, Dónall

    2009-01-01

    BACKGROUND: Warfarin is an oral anticoagulant (OAT) that needs active management to ensure therapeutic range. Initial management is often carried out as an inpatient, though not requiring inpatient facilities. This mismatch results in financial costs which could be directed more efficaciously. The extent of this has previously been unknown. Here we aim to calculate the potential number of bed nights which may be saved among those being dose optimized as inpatients and examine associated factors. METHODS: A 6 week prospective audit of inpatients receiving OAT, at Cork University Hospital, was carried out. The study period was from 11th June 2007 to 20th July 2007. Data was collected from patient\\'s medications prescription charts, medical record files, and computerised haematology laboratory records. The indications for OAT, the patient laboratory coagulation results and therapeutic intervals along with patient demographics were analysed. The level of potentially avoidable inpatient nights in those receiving OAT in hospital was calculated and the potential cost savings quantified. Potential avoidable bed nights were defined as patients remaining in hospital for the purpose of optimizing OAT dosage, while receiving subtherapeutic or therapeutic OAT (being titred up to therapeutic levels) and co-administered covering low molecular weight heparin, and requiring no other active care. The average cost of euro638 was taken as the per night hospital stay cost for a non-Intensive Care bed. Ethical approval was granted from the Ethical Committee of the Cork Teaching Hospitals, Cork, Ireland. RESULTS: A total of 158 patients were included in the audit. There was 94 men (59.4%) and 64 women (40.6%). The mean age was 67.8 years, with a median age of 70 years.Atrial Fibrillation (43%, n = 70), followed by aortic valve replacement (15%, n = 23) and pulmonary emboli (11%, n = 18) were the commonest reasons for prescribing OAT. 54% had previously been prescribed OAT prior to

  11. Patient satisfaction after switching from warfarin to apixaban in patients with nonvalvular atrial fibrillation: AGAIN study

    Directory of Open Access Journals (Sweden)

    Koretsune Y

    2017-12-01

    Full Text Available Yukihiro Koretsune,1 Takanori Ikeda,2 Ken Kozuma,3 Teruyuki Hirano,4 Masahiro Yasaka,5 Makoto Kida,6 Motohiko Chachin,7 Miki Imura7 1National Hospital Organization, Osaka National Hospital, Osaka, 2Department of Cardiovascular Medicine, Toho University Graduate School of Medicine, Toho University, Tokyo, 3Division of Cardiology, Teikyo University School of Medicine, Teikyo University, Tokyo, 4Department of Stroke and Cerebrovascular Medicine, Kyorin University, Tokyo, 5Department of Cerebrovascular Medicine and Neurology, National Hospital Organization, Kyushu Medical Center, Fukuoka, 6Medical & Development, Bristol-Myers Squibb K.K., Tokyo, 7Pfizer Innovative Health Medical Affairs, Pfizer Japan Inc., Tokyo, Japan Purpose: Patients treated with warfarin must adhere to frequent monitoring, dietary restrictions, and complicated dose adjustments. Apixaban, a direct factor Xa inhibitor, is an alternative to warfarin that may reduce patient burdens associated with warfarin therapy. However, there is limited evidence pertaining to patient satisfaction with anticoagulant therapies in Japanese patients. The purpose of this observational study was to investigate changes in patient satisfaction after switching from warfarin to apixaban.Patients and methods: Nonvalvular atrial fibrillation (NVAF patients who were scheduled to switch anticoagulants from warfarin to apixaban were enrolled and treated with apixaban for 12 weeks. Patient satisfaction was assessed before the change in medication and after 12 weeks of treatment with apixaban using the Anti-Clot Treatment Scale (ACTS, a patient-reported instrument for measuring satisfaction with anticoagulation treatment. The ACTS includes a 12-item burden scale (maximum 60 points and a 3-item benefit scale (maximum 15 points.Results: Among 732 NVAF patients enrolled, the full analysis set consisted of 697 patients who completed two ACTS assessments (one before the medication change and one 12 weeks after the

  12. The accuracy of warfarin dosage based on VKORC1 and CYP2C9 phenotypes in a Chinese population

    Directory of Open Access Journals (Sweden)

    Agustinus Wijaya

    2012-05-01

    Full Text Available Background: The aim of this study is to assess the accuracy of warfarin dosage based on VKORC1 and CYP2C9 genotype in Chinese population.Methods: Blood samples were taken from 37 patients. We compared the warfarin dosage obtained from genotype (according to www.warfarindosing.org and treatment dosage with international normalized ratio (INR value within 2.0-3.0.Results: The majority of Chinese people in our study are VKORC1 homozygous AA (89.2%, rarely VKORC1 heterozygous AG and we cannot find a patient with homozygous GG. For CYP2C9 genotype, most patients have the wildtype variants (CYP2C9*2 CC and CYP2C9*3 AA. The warfarin dosage for patients with VKORC1 AA and CYP2C9*3 AC is lower than for patients with other genotype variants.Conclusion: There is no significant difference between pharmacogenetic algorithm (www.warfarindosing.org and our treatment dosage. Our conclusion is that the pharmacogenetic algorithm is accurate to predict the warfarin dose. (Med J Indones. 2012;21:108-12Keywords: CYP2C9, pharmacogenetic algorithm, VKORC1, warfarin

  13. Warfarin Dosing Algorithms Underpredict Dose Requirements in Patients Requiring ≥7 mg Daily: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Saffian, S M; Duffull, S B; Wright, Dfb

    2017-08-01

    There is preliminary evidence to suggest that some published warfarin dosing algorithms produce biased maintenance dose predictions in patients who require higher than average doses. We conducted a meta-analysis of warfarin dosing algorithms to determine if there exists a systematic under- or overprediction of dose requirements for patients requiring ≥7 mg/day across published algorithms. Medline and Embase databases were searched up to September 2015. We quantified the proportion of over- and underpredicted doses in patients whose observed maintenance dose was ≥7 mg/day. The meta-analysis included 47 evaluations of 22 different warfarin dosing algorithms from 16 studies. The meta-analysis included data from 1,492 patients who required warfarin doses of ≥7 mg/day. All 22 algorithms were found to underpredict warfarin dosing requirements in patients who required ≥7 mg/day by an average of 2.3 mg/day with a pooled estimate of underpredicted doses of 92.3% (95% confidence interval 90.3-94.1, I 2 = 24%). © 2017 American Society for Clinical Pharmacology and Therapeutics.

  14. TRial of an Educational intervention on patients' knowledge of Atrial fibrillation and anticoagulant therapy, INR control, and outcome of Treatment with warfarin (TREAT

    Directory of Open Access Journals (Sweden)

    Pattison Helen M

    2010-05-01

    Full Text Available Abstract Background Atrial fibrillation (AF patients with a high risk of stroke are recommended anticoagulation with warfarin. However, the benefit of warfarin is dependent upon time spent within the target therapeutic range (TTR of their international normalised ratio (INR (2.0 to 3.0. AF patients possess limited knowledge of their disease and warfarin treatment and this can impact on INR control. Education can improve patients' understanding of warfarin therapy and factors which affect INR control. Methods/Design Randomised controlled trial of an intensive educational intervention will consist of group sessions (between 2-8 patients containing standardised information about the risks and benefits associated with OAC therapy, lifestyle interactions and the importance of monitoring and control of their International Normalised Ratio (INR. Information will be presented within an 'expert-patient' focussed DVD, revised educational booklet and patient worksheets. 200 warfarin-naïve patients who are eligible for warfarin will be randomised to either the intervention or usual care groups. All patients must have ECG-documented AF and be eligible for warfarin (according to the NICE AF guidelines. Exclusion criteria include: aged Discussion More data is needed on the clinical benefit of educational intervention with AF patients receiving warfarin. Trial registration ISRCTN93952605

  15. The role of the transition between neutral and basic forms of human serum albumin in the kinetics of the binding to warfarin

    NARCIS (Netherlands)

    Kremer, J.M.H.; Bakker, G.; Wilting, J.

    1982-01-01

    Between pH 6 and 9 in the kinetics of the binding of warfarin to human serum albumin a two-step mechanism operates: a diffusion-controlled step, followed by a much slower step during which the stable warfarin-albumin complex is formed. The association rate constant for the formation of the

  16. Clinical events after transitioning from apixaban versus warfarin to warfarin at the end of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

    Science.gov (United States)

    Granger, Christopher B; Lopes, Renato D; Hanna, Michael; Ansell, Jack; Hylek, Elaine M; Alexander, John H; Thomas, Laine; Wang, Junyuan; Bahit, M Cecilia; Verheugt, Freek; Lawrence, Jack; Xavier, Denis; Wallentin, Lars

    2015-01-01

    We sought to assess the occurrence of events after blinded study drug discontinuation and transition to open-label vitamin K antagonist (VKA) in ARISTOTLE. At the end of ARISTOTLE, blinded study drug was stopped, and open-label VKA was recommended. For patients completing the trial on blinded study drug, a 2-day bridging period with apixaban or apixaban placebo was recommended (while beginning open-label VKA). Outcomes were assessed during the 30 days after stopping blinded study drug. Of the 6,809 patients in the apixaban group and 6,588 in the warfarin group who completed the trial on study drug, there were 21 strokes or systemic emboli (4.02%/year) and 26 major bleeding (4.97%/year) events in the apixaban group (transitioning to VKA) and 5 strokes or systemic emboli (0.99%/year) and 10 major bleeding (1.97%/year) events in the warfarin group (continuing on VKA), with most of the imbalance between groups being after the first week. Similar results were seen in the first 30 days of the trial where warfarin-naive patients starting warfarin had a higher rate of stroke or systemic emboli (5.41%/year) than warfarin-experienced patients (1.42%/year), a pattern not seen when starting apixaban. No similar increase in events with apixaban versus warfarin was seen during temporary or permanent study drug discontinuation during the trial. The excess in thrombotic and bleeding events in the apixaban group after study drug discontinuation appears to be related to an increased risk associated with the initiation of a VKA rather than a direct effect of apixaban. Whether ≥2 days of apixaban bridging improves outcomes during VKA transition is unknown and deserves further evaluation. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. A role for pharmacists in community-based post-discharge warfarin management: protocol for the 'the role of community pharmacy in post hospital management of patients initiated on warfarin' study

    Directory of Open Access Journals (Sweden)

    Bereznicki Luke RE

    2011-01-01

    Full Text Available Abstract Background Shorter periods of hospitalisation and increasing warfarin use have placed stress on community-based healthcare services to care for patients taking warfarin after hospital discharge, a high-risk period for these patients. A previous randomised controlled trial demonstrated that a post-discharge service of 4 home visits and point-of-care (POC International Normalised Ratio (INR testing by a trained pharmacist improved patients' outcomes. The current study aims to modify this previously trialled service model to implement and then evaluate a sustainable program to enable the smooth transition of patients taking warfarin from the hospital to community setting. Methods/Design The service will be trialled in 8 sites across 3 Australian states using a prospective, controlled cohort study design. Patients discharged from hospital taking warfarin will receive 2 or 3 home visits by a trained 'home medicines review (HMR-accredited' pharmacist in their 8 to 10 days after hospital discharge. Visits will involve a HMR, comprehensive warfarin education, and POC INR monitoring in collaboration with patients' general practitioners (GPs and community pharmacists. Patient outcomes will be compared to those in a control, or 'usual care', group. The primary outcome measure will be the proportion of patients experiencing a major bleeding event in the 90 days after discharge. Secondary outcome measures will include combined major bleeding and thromboembolic events, death, cessation of warfarin therapy, INR control at 8 days post-discharge and unplanned hospital readmissions from any cause. Stakeholder satisfaction will be assessed using structured postal questionnaire mailed to patients, GPs, community pharmacists and accredited pharmacists at the completion of their study involvement. Discussion This study design incorporates several aspects of prior interventions that have been demonstrated to improve warfarin management, including POC INR

  18. Low-dose warfarin coupled with lower leg compression is effective prophylaxis against thromboembolic disease after hip arthroplasty.

    Science.gov (United States)

    Bern, Murray; Deshmukh, Rahul V; Nelson, Russell; Bierbaum, Benjamin; Sevier, Nancy; Howie, Noreen; Losina, Elena; Katz, Jeffrey N

    2007-08-01

    Consecutive patients having elective total hip arthroplasty were prescribed 1 mg of warfarin for 7 days preceding surgery, variable doses while in hospital (target international normalized ratio, 1.5-2.0), and discharged to rehabilitation center or home taking 1 mg daily until 4-week to 6-week follow-up visit. Lower leg pneumatic compression was used postoperatively and elastic compression stockings after discharge. Hospital and clinic charts plus auxiliary sources were reviewed for evidence of thromboembolic diseases (TED). Of 1003 consecutive patients studied, 3 (0.3%, 95% CI 0.0-0.6%) had symptomatic TED, including 2 with deep venous thrombosis and 1 with nonfatal pulmonary embolus. Follow-up rate was 99.1%. Complications from warfarin were minimal. Very-low-dose warfarin coupled with lower leg compression is effective prophylaxis against TED after elective hip arthroplasty when prescribed as described.

  19. Fluorescence Determination of Warfarin Using TGA-capped CdTe Quantum Dots in Human Plasma Samples.

    Science.gov (United States)

    Dehbozorgi, A; Tashkhourian, J; Zare, S

    2015-11-01

    In this study, some effort has been performed to provide low temperature, less time consuming and facile routes for the synthesis of CdTe quantum dots using ultrasound and water soluble capping agent thioglycolic acid. TGA-capped CdTe quantum dots were characterized through x-ray diffraction, transmission electron microscopy, Fourier transform infrared, ultraviolet-visible and fluorescence spectroscopy. The prepared quantum dots were used for warfarin determination based on the quenching of the fluorescence intensity in aqueous solution. Under the optimized conditions, the linear range of quantum dots fluorescence intensity versus the concentration of warfarin was 0.1-160.0 μM, with the correlation coefficient of 0.9996 and a limit of detection of 77.5 nM. There was no interference to coexisting foreign substances. The selectivity of the sensor was also tested and the results show that the developed method possesses a high selectivity for warfarin.

  20. Provider and pharmacist responses to warfarin drug–drug interaction alerts: a study of healthcare downstream of CPOE alerts

    Science.gov (United States)

    Boro, Maureen S; Korman, Nancy E; Davoren, J Ben

    2011-01-01

    Objective To categorize the appropriateness of provider and pharmacist responses to warfarin critical drug–drug interaction (cDDI) alerts, assess responses and actions to the cDDI, and determine the occurrence of warfarin adverse drug events (ADE) after alerts. Design An 18-month, retrospective study of acute care admissions at a single Veterans Affairs medical center using computerized provider order entry (CPOE). Measurements Patients included had at least one warfarin cDDI alert. Chart reviews included baseline laboratory values and demographics, provider actions, patient outcomes, and associated factors, including other interacting medications and number of simultaneously processed alerts. Results 137 admissions were included (133 unique patients). Amiodarone, vitamin E in a multivitamin, sulfamethoxazole, and levothyroxine accounted for 75% of warfarin cDDI. Provider responses were clinically appropriate in 19.7% of admissions and pharmacist responses were appropriate in 9.5% of admissions. There were 50 ADE (36.6% of admissions) with warfarin; 80% were rated as having no or mild clinical effect. An increased number of non-critical alerts at the time of the reference cDDI alert was the only variable associated with an inappropriate provider response (p=0.01). Limitations This study was limited by being a retrospective review and the possibility of confounding variables, such as other interacting medications. Conclusion The large number of CPOE alerts may lead to inappropriate responses by providers and pharmacists. The high rate of ADE suggests a need for improved medication management systems for patients on warfarin. This study highlights the possibility of alert fatigue contributing to the high prevalence of inappropriate alert over-ride text responses. PMID:22037888

  1. Health literacy and warfarin therapy at two anticoagulation clinics in Brazil.

    Science.gov (United States)

    Martins, Maria Auxiliadora Parreiras; Costa, Josiane Moreira; Mambrini, Juliana Vaz de Melo; Ribeiro, Antonio Luiz Pinho; Benjamin, Emelia J; Brant, Luisa Campos Caldeira; Paasche-Orlow, Michael K; Magnani, Jared W

    2017-07-01

    Health literacy has been related to health-related conditions and health outcomes. Studies examining the association of health literacy and anticoagulation have had variable results. We sought to investigate the relations of health literacy and percentage of time in therapeutic range (TTR) in a vulnerable Brazilian cohort at two hospital-based anticoagulation clinics. We measured health literacy with the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA-18) in 2015-2016. We identified the demographic and clinical characteristics associated with health literacy and related health literacy to TTR. We enrolled 422 adults prescribed chronic warfarin therapy in our observational study (median age 62.1 years; 58.8% women; monthly income $200.00). The prevalence of inadequate health literacy (score 0-14 points) was 72.3% with a median score of 12 (quartiles, Q1=10; Q3=15) on the SAHLPA-18. The median TTR was 66.1%. In the multivariable logistic analysis, cognitive impairment and assistance with taking warfarin were associated with inadequate health literacy. Prosthetic heart valves and more school years were associated with adequate health literacy. Our analyses showed no significant relation between health literacy and TTR, analysing health literacy as a categorical (adjusted OR 1.05; 95% CI 0.65 to 1.70) or continuous variable (Spearman's coefficient 0.02; p=0.70). Inadequate health literacy was highly prevalent in this impoverished Brazilian cohort receiving anticoagulation with warfarin. However, we did not identify an association between health literacy and TTR. Future investigations may consider the systemic factors that contribute towards successful anticoagulation outcomes for vulnerable patient cohorts with inadequate health literacy. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Oral Cancer

    Science.gov (United States)

    Oral cancer can form in any part of the mouth. Most oral cancers begin in the flat cells that cover the ... your mouth, tongue, and lips. Anyone can get oral cancer, but the risk is higher if you are ...

  3. Pregnancy outcome after maternal poisoning with brodifacoum, a long-acting warfarin-like rodenticide.

    Science.gov (United States)

    Zurawski, J M; Kelly, E A

    1997-10-01

    Brodifacoum is a potent warfarin-like anticoagulant used in many rat-poisoning products. Its availability has led to several reported human ingestions, none previously reported in pregnancy. A woman presented at 22 weeks' gestation in hemorrhagic diathesis, attributed to the ingestion of rat poison containing brodifacoum several days earlier. Aggressive vitamin K therapy controlled the maternal coagulopathy, and no fetal hemorrhage was observed by sonography. Her subsequent prenatal course and delivery were unremarkable, and she was delivered of a healthy infant, who has remained well for at least 1 year. In this patient, brodifacoum ingestion in pregnancy caused substantial maternal hemorrhage, but no fetal hemorrhage or teratogenic effects were observed.

  4. Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study

    Science.gov (United States)

    Perera, Minoli A; Cavallari, Larisa H; Limdi, Nita A; Gamazon, Eric R; Konkashbaev, Anuar; Daneshjou, Roxana; Pluzhnikov, Anna; Crawford, Dana C; Wang, Jelai; Liu, Nianjun; Tatonetti, Nicholas; Bourgeois, Stephane; Takahashi, Harumi; Bradford, Yukiko; Burkley, Benjamin M; Desnick, Robert J; Halperin, Jonathan L; Khalifa, Sherief I; Langaee, Taimour Y; Lubitz, Steven A; Nutescu, Edith A; Oetjens, Matthew; Shahin, Mohamed H; Patel, Shitalben R; Sagreiya, Hersh; Tector, Matthew; Weck, Karen E; Rieder, Mark J; Scott, Stuart A; Wu, Alan HB; Burmester, James K; Wadelius, Mia; Deloukas, Panos; Wagner, Michael J; Mushiroda, Taisei; Kubo, Michiaki; Roden, Dan M; Cox, Nancy J; Altman, Russ B; Klein, Teri E; Nakamura, Yusuke; Johnson, Julie A

    2013-01-01

    Summary Background VKORC1 and CYP2C9 are important contributors to warfarin dose variability, but explain less variability for individuals of African descent than for those of European or Asian descent. We aimed to identify additional variants contributing to warfarin dose requirements in African Americans. Methods We did a genome-wide association study of discovery and replication cohorts. Samples from African-American adults (aged ≥18 years) who were taking a stable maintenance dose of warfarin were obtained at International Warfarin Pharmacogenetics Consortium (IWPC) sites and the University of Alabama at Birmingham (Birmingham, AL, USA). Patients enrolled at IWPC sites but who were not used for discovery made up the independent replication cohort. All participants were genotyped. We did a stepwise conditional analysis, conditioning first for VKORC1 −1639G→A, followed by the composite genotype of CYP2C9*2 and CYP2C9*3. We prespecified a genome-wide significance threshold of p<5×10−8 in the discovery cohort and p<0·0038 in the replication cohort. Findings The discovery cohort contained 533 participants and the replication cohort 432 participants. After the prespecified conditioning in the discovery cohort, we identified an association between a novel single nucleotide polymorphism in the CYP2C cluster on chromosome 10 (rs12777823) and warfarin dose requirement that reached genome-wide significance (p=1·51×10−8). This association was confirmed in the replication cohort (p=5·04×10−5); analysis of the two cohorts together produced a p value of 4·5×10−12. Individuals heterozygous for the rs12777823 A allele need a dose reduction of 6·92 mg/week and those homozygous 9·34 mg/week. Regression analysis showed that the inclusion of rs12777823 significantly improves warfarin dose variability explained by the IWPC dosing algorithm (21% relative improvement). Interpretation A novel CYP2C single nucleotide polymorphism exerts a clinically relevant

  5. Determination of acid dissociation constants of warfarin and hydroxywarfarins by capillary electrophoresis.

    Science.gov (United States)

    Nowak, Paweł; Olechowska, Paulina; Mitoraj, Mariusz; Woźniakiewicz, Michał; Kościelniak, Paweł

    2015-08-10

    In this work the acid dissociation constants--pKa of warfarin and its all important oxidative metabolites have been determined by capillary electrophoresis-based methods. It has resulted in a complete description of two acid-base dissociation equilibria, yet not investigated experimentally for phase I metabolites of warfarin. The capillary electrophoresis (CE) method based on the relation between effective electrophoretic mobilities and pH has proven to be a suitable tool for pKa determination, while the spectrophotometric (CE-DAD) and the internal standard methods (IS-CE), have appeared to be promising alternative approaches. The CE-DAD approach based on the change in absorbance spectra between the acidic and basic forms is a combination between capillary electrophoresis and spectrophotometric titration, and yields very consistent values of pKa1 with CE. The IS-CE, in turn, enables an estimation of pKa1 and pKa2 from only two analytical runs, however, less accurate than CE and CE-DAD. The Debye-Hückel model has been confirmed experimentally as a good predictor of pKa values at various ionic strengths. Therefore, it has been used in determination of thermodynamic pKa1 and pKa2, referring to the zero ionic strength. The results are important from the analytical, pharmacological, and theoretical points of view. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Dentists' approach to patients on anti-platelet agents and warfarin: a survey of practice.

    LENUS (Irish Health Repository)

    Murphy, James

    2010-04-23

    In everyday practice, dentists are confronted with the dilemma of patients on anti-platelet agents and warfarin who require invasive dental procedures and, more pertinently, dental extractions. There may be a divergence of opinion among dentists regarding how they manage these patients. AIMS: To assess general dental practitioners\\' approach to the management of patients taking anti-platelet agents and\\/or warfarin who are undergoing invasive dental procedures. METHODS AND DATA: A semi-structured questionnaire was designed to survey general dental practitioners in a large Irish urban area. RESULTS: A response rate of 89% was achieved in a study population of 54 general dental practitioners. A total of 25% of respondents who carry out extractions on warfarinised patients do not check the INR prior to invasive dental procedures. Some 90% of respondents stop anti-platelet agents prior to extractions. CONCLUSIONS: A significant proportion of respondents fail to check warfarinised patients\\' INR prior to invasive dental procedures. Furthermore, a trend of stopping anti-platelet agents was noted, which is in contrast with current recommendations in the dental literature. Certain practices in this small study population proved alarming and highlight the need for improved awareness of current guidelines. A further large-scale study may be justified, as variation in practice may have clinical and medico-legal repercussions.

  7. Combination of lenalidomide and low-dose dexamethasone therapy promotes the anticoagulant activity of warfarin in patients with immunoglobulin light-chain amyloidosis.

    Science.gov (United States)

    Kitazawa, Fumiaki; Fuchida, Shin-Ichi; Ise, Fumitaka; Kado, Yoko; Ueda, Kumi; Kokufu, Takatoshi; Okano, Akira; Hatsuse, Mayumi; Murakami, Satoshi; Nakayama, Yuko; Takara, Kohji; Shimazaki, Chihiro

    2017-07-01

    The present study aimed to evaluate the drug interactions between warfarin and combination chemotherapy with lenalidomide and low-dose dexamethasone in immunoglobulin light-chain (AL) amyloidosis patients with unstable international normalized ratios (INR). The changes to INR values over time in 3 AL amyloidosis patients treated with warfarin and a combination of lenalidomide and low-dose dexamethasone between March 2011 and February 2015 were analyzed retrospectively. The mean INR value was 1.52 prior to the combination chemotherapy, and the value increased 1.7-fold during treatment. The median time to reach maximum values was 17 days. Horn's drug Interaction Probability Scale indicated a possible interaction between lenalidomide and warfarin. These patients exhibited no marked alterations in hepatic function or serum albumin concentrations prior to and following combination chemotherapy and no additional administration of CYP2C9 inhibitors or vitamin K supplements was conducted. In addition, no patient experienced chemotherapy-induced nausea or appetite loss. These findings suggest that the total clearance or protein binding of warfarin remained unchanged. Therefore, the combination of warfarin and lenalidomide may cause a pharmacodynamic interaction, more likely by inhibiting the production of interleukin-6. In conclusion, clinically important interactions between warfarin and lenalidomide and low-dose dexamethasone therapy were observed in AL amyloidosis patients, where INR values signi ficantly increased. Therefore, close and regular monitoring of patients during the course of treatment is important, and the dose of warfarin should be reduced if required.

  8. Cost Effectiveness of Genotype-Guided Warfarin Dosing in Patients with Mechanical Heart Valve Replacement Under the Fee-for-Service System.

    Science.gov (United States)

    Kim, Dong-Jin; Kim, Ho-Sook; Oh, Minkyung; Kim, Eun-Young; Shin, Jae-Gook

    2017-10-01

    Although studies assessing the cost effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation, deep vein thrombosis, and pulmonary embolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin therapy under the fee-for-service (FFS) insurance system. The aim of this study was to evaluate the cost effectiveness of genotype-guided warfarin dosing in patients with MHVR under the FFS system from the Korea healthcare sector perspective. A decision-analytic Markov model was developed to evaluate the cost effectiveness of genotype-guided warfarin dosing compared with standard dosing. Estimates of clinical adverse event rates and health state utilities were derived from the published literature. The outcome measure was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed to explore the range of plausible results. In a base-case analysis, genotype-guided warfarin dosing was associated with marginally higher QALYs than standard warfarin dosing (6.088 vs. 6.083, respectively), at a slightly higher cost (US$6.8) (year 2016 values). The ICER was US$1356.2 per QALY gained. In probabilistic sensitivity analysis, there was an 82.7% probability that genotype-guided dosing was dominant compared with standard dosing, and a 99.8% probability that it was cost effective at a willingness-to-pay threshold of US$50,000 per QALY gained. Compared with only standard warfarin therapy, genotype-guided warfarin dosing was cost effective in MHVR patients under the FFS insurance system.

  9. Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients

    DEFF Research Database (Denmark)

    Li, Xiaoyan; Keshishian, Allison; Hamilton, Melissa

    2018-01-01

    Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbe...

  10. Can We Predict Individual Combined Benefit and Harm of Therapy? Warfarin Therapy for Atrial Fibrillation as a Test Case.

    Directory of Open Access Journals (Sweden)

    Guowei Li

    Full Text Available To construct and validate a prediction model for individual combined benefit and harm outcomes (stroke with no major bleeding, major bleeding with no stroke, neither event, or both in patients with atrial fibrillation (AF with and without warfarin therapy.Using the Kaiser Permanente Colorado databases, we included patients newly diagnosed with AF between January 1, 2005 and December 31, 2012 for model construction and validation. The primary outcome was a prediction model of composite of stroke or major bleeding using polytomous logistic regression (PLR modelling. The secondary outcome was a prediction model of all-cause mortality using the Cox regression modelling.We included 9074 patients with 4537 and 4537 warfarin users and non-users, respectively. In the derivation cohort (n = 4632, there were 136 strokes (2.94%, 280 major bleedings (6.04% and 1194 deaths (25.78% occurred. In the prediction models, warfarin use was not significantly associated with risk of stroke, but increased the risk of major bleeding and decreased the risk of death. Both the PLR and Cox models were robust, internally and externally validated, and with acceptable model performances.In this study, we introduce a new methodology for predicting individual combined benefit and harm outcomes associated with warfarin therapy for patients with AF. Should this approach be validated in other patient populations, it has potential advantages over existing risk stratification approaches as a patient-physician aid for shared decision-making.

  11. Oral Anticoagulant Use After Bariatric Surgery: A Literature Review and Clinical Guidance.

    Science.gov (United States)

    Martin, Karlyn A; Lee, Craig R; Farrell, Timothy M; Moll, Stephan

    2017-05-01

    Bariatric surgery may alter the absorption, distribution, metabolism, or elimination (disposition) of orally administered drugs via changes to the gastrointestinal tract anatomy, body weight, and adipose tissue composition. As some patients who have undergone bariatric surgery will need therapeutic anticoagulation for various indications, appropriate knowledge is needed regarding anticoagulant drug disposition and resulting efficacy and safety in this population. We review general considerations about oral drug disposition in patients after bariatric surgery, as well as existing literature on oral anticoagulation after bariatric surgery. Overall, available evidence on therapeutic anticoagulation is very limited, and individual drug studies are necessary to learn how to safely and effectively use the direct oral anticoagulants. Given the sparsity of currently available data, it appears most prudent to use warfarin with international normalized ratio monitoring, and not direct oral anticoagulants, when full-dose anticoagulation is needed after bariatric surgery. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Increased short-term risk of thrombo-embolism or death after interruption of warfarin treatment in patients with atrial fibrillation

    DEFF Research Database (Denmark)

    Raunsø, Jakob; Selmer, Christian; Olesen, Jonas Bjerring

    2012-01-01

    . In total, 48 989 AF patients receiving warfarin treatment were included. Of these, 35 396 patients had at least one episode of warfarin treatment interruption. In all, 8255 deaths or thrombo-embolic events occurred during treatment interruption showing an initial clustering of events with 2717, 835, 500...... was associated with a markedly higher risk of death or thrombo-embolism (IRR 2.5; 95% confidence interval 2.3-2.8) vs. the interval of 271-360 days. CONCLUSION: In patients with AF, an interruption of warfarin treatment is associated with a significantly increased short-term risk of death or thrombo...

  13. Pharmacogenetic versus clinical dosing of warfarin in individuals of Chinese and African-American ancestry: assessment using data simulation.

    Science.gov (United States)

    Syn, Nicholas L X; Lee, Soo-Chin; Brunham, Liam R; Goh, Boon-Cher

    2015-10-01

    Clinical trials of genotype-guided dosing of warfarin have yielded mixed results, which may in part reflect ethnic differences among study participants. However, no previous study has compared genotype-guided versus clinically guided or standard-of-care dosing in a Chinese population, whereas those involving African-Americans were underpowered to detect significant differences. We present a preclinical strategy that integrates pharmacogenetics (PG) and pharmacometrics to predict the outcome or guide the design of dosing strategies for drugs that show large interindividual variability. We use the example of warfarin and focus on two underrepresented groups in warfarin research. We identified the parameters required to simulate a patient population and the outcome of dosing strategies. PG and pharmacogenetic plus loading (PG+L) algorithms that take into account a patient's VKORC1 and CYP2C9 genotype status were considered and compared against a clinical (CA) algorithm for a simulated Chinese population using a predictive Monte Carlo and pharmacokinetic-pharmacodynamic framework. We also examined a simulated population of African-American ancestry to assess the robustness of the model in relation to real-world clinical trial data. The simulations replicated similar trends observed with clinical data in African-Americans. They further predict that the PG+L regimen is superior to both the CA and the PG regimen in maximizing percentage time in therapeutic range in a Chinese cohort, whereas the CA regimen poses the highest risk of overanticoagulation during warfarin initiation. The findings supplement the literature with an unbiased comparison of warfarin dosing algorithms and highlights interethnic differences in anticoagulation control.

  14. First report of warfarin dose requirements in patients possessing the CYP2C9*12 allele.

    Science.gov (United States)

    O'Brien, Travis J; Kidd, Robert S; Richard, Craig A H; Ha, Ngoc-Han; Witcher, Preston; Tran, Linda V; Barbour, April; Tuck, Matthew; McIntosh, Samantha D; Douglas, Jacqueline N; Harralson, Arthur F

    2013-09-23

    Warfarin is the most frequently prescribed anticoagulant in North America and Europe. It is administered as a racemate, but S-warfarin is principally responsible for its anticoagulant activity. Cytochrome P450 (CYP) 2C9 is the enzyme primarily responsible for the metabolism of S-warfarin. Numerous variant alleles of CYP2C9 have been identified. The CYP2C9*12 (rs9332239) allele harbors a P489S substitution in CYP2C9 which has been shown to result in a 40% decline in catalytic activity in vitro. Four Caucasian patients with a low mean weekly warfarin dose (MWWD) were genotyped for CYP2C9, VKORC1 and APOE variant alleles. None of the four patients carried the common CYP2C9 variant alleles (*2, *3, *5, *6, *7, *8, *9, *11, *13) despite a relatively low MWWD (23.4±7.94 mg) compared to 208 patients carrying the CYP29C9*1 genotype (32.2±12.65 mg). Given that CYP2C9*12 confers decreased in vitro activity to the enzyme, we investigated whether these patients carried this allele. All four patients were CYP2C9*12 CT heterozygotes. Individual comparisons with patients possessing the same VKORC1 and APOE genotypes also demonstrated lower dose requirements in the patients that possessed CYP2C9*12 allele. There are no reports of the clinical impact of rs9332239 on CYP2C9 substrates. This is the first report of patients with the rare CYP2C9*12 genotype and lower warfarin dose requirements. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Varfarina ou Aspirina na prevenção de fenômenos embólicos na valvopatia mitral com fibrilação atrial Varfarina o aspirina en la prevención de fenómenos embólicos en la valvopatía mitral con fibrilación atrial Warfarin or Aspirin in embolism prevention in patients with mitral valvulopathy and atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Paulo de Lara Lavitola

    2010-12-01

    effectiveness of Aspirin vs Warfarin in TE prevention in patients with AF and RMVD. METHODS: A total of 229 patients (pts with AF and RMVD were followed in a prospective and randomized study. The first group consisted of 110 pts receiving Aspirin - 200 mg/day (Group Aspirin - GA and the second group consisted of 119 pts receiving Warfarin at individually-adjusted doses (Group Warfarin - GW. RESULTS: There were 15 embolic events in GA and 24 in GW (p = 0.187, of which 21 presented INR < 2.0. Thus, after excluding patients with inadequate INR, there was a higher number of embolic events in GA than in GW (15 vs 3 (p < 0.0061. The GW showed lower treatment adherence (p = 0.001. Neither group presented episodes of major bleeding. Small bleeding episodes were more frequent in the GW (p < 0.01. Increased serum levels of cholesterol and triglycerides constituted a risk factor for a higher number of thromboembolic events in the studied population, with no difference between the groups. CONCLUSION: In patients presenting RMVD with AF for less than a year and no previous embolism, Aspirin is little effective in preventing TE. Patients with lower-risk mitral valvulopathy (mitral regurgitation and mitral biological prosthesis, especially in cases presenting contraindication to or low adherence to Warfarin, Aspirin use can present some benefit in TE prevention.

  16. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Thalaimalai Saravanan

    2015-01-01

    Full Text Available Myiasis is a pathologic condition in humans occurring because of parasitic infestation. Parasites causing myiasis belong to the order Diptera. Oral myiasis is seen secondary to oral wounds, suppurative lesions, and extraction wounds, especially in individuals with neurological deficit. In such cases, neglected oral hygiene and halitosis attracts the flies to lay eggs in oral wounds resulting in oral myiasis. We present a case of oral myiasis in 40-year-old male patient with mental disability and history of epilepsy.

  17. Battle of oral anticoagulants in the field of atrial fibrillation scrutinized from a clinical practice (the real world perspective

    Directory of Open Access Journals (Sweden)

    Vidal Hector O

    2011-07-01

    Full Text Available Abstract Warfarin has a long history of benefit and has become the gold standard medication for the prevention of ischemic stroke in patients with atrial fibrillation. Nevertheless, it is far from perfect and there is no doubt that new drugs must be found to replace warfarin. The new oral anticoagulants that are on the market or awaiting approval or under research offer some benefits but not enough to replace warfarin until results of additional studies can show an adequate balance between effectiveness/safety and cost/benefit. There are several issues concerning the new oral anticoagulants. It is essential that the effect of any anticoagulant can be measured in plasma. But to date, there is no test to assess the effect or therapeutic range for the new oral anticoagulants. There is no antidote to neutralize the action of the new drugs in cases of bleeding or when acute surgical intervention is necessary. Dabigatran requires dose adjustment in patients with moderate renal impairment and is contraindicated in patients with severe renal failure. Rivaroxaban should be used with caution in patients with severe renal impairment. Apixaban excretion is also partly dependent on renal function, although the impact of renal insufficiency has not yet been determined. How anticoagulant bridging can be done before surgery has not yet been established. In conclusion, although thousands of patients have been treated in phase III studies, additional data are necessary before conclusions can be drawn on the potential for these new anticoagulant drugs to replace warfarin in patients with atrial fibrillation.

  18. The Role of Warfarin Alone or in Combination with Certain Natural Products Against Blood Disorders Induced by Gamma Radiation in Experimental Animals

    International Nuclear Information System (INIS)

    Fahim, M.G.; Radwan, R.R.; Shaaban, E.A.; El-Denshary, E.S.

    2016-01-01

    The effect of warfarin against blood disorder induced by radiation and possible effect of certain natural products in modifying anticoagulant effect of warfarin in irradiated rats was investigated. Prothrombin time (PT), international normalized ratio (INR), partial thromboplastin time (PTT), thrombin time (TT), fibrinogen level and platelet count were evaluated. Furthermore, plasma level of malondialdehyde (MDA), reduced glutathione (GSH) and nitric oxide (NO) were determined. The obtained data showed that irradiation elevated Pt, INR, PTT, TT and fibrinogen level. Moreover, irradiation increased MDA and NO levels while, reduced GSH level. It was found that administration of garlic, fenugreek or green tea with warfarin for one week before irradiation resulted in elevation in PT and INR. Results suggest that patients on warfarin and exposed to radiation are specifically advised to avoid taking herbal medicines or to have their PT and INR measured within two weeks of starting the drug, to be on a safer side

  19. A prospective study of an aggressive warfarin dosing algorithm to reach and maintain INR 2 to 3 after heart valve surgery

    NARCIS (Netherlands)

    Meijer, Karina; Kim, Yang-Ki; Carter, Donna; Schulman, Sam

    Good anticoagulation control in patients during the first months after heart valve surgery is important to prevent thrombotic complications. This is difficult to achieve, partly because the sensitivity to warfarin decreases progressively during approximately three months after valve surgery. A

  20. Hydrogen-deuterium (h-d) exchange reaction of warfarin in D(2)O solution.

    Science.gov (United States)

    Tode, Chisato; Takeuchi, Atsuko; Iwakawa, Seigo; Tatsumi, Akitoshi; Sugiura, Makiko

    2009-07-01

    To prove the presence of a hydrogen-deuterium (H-D) exchange reaction, (1)H- and (13)C-NMR spectra of warfarin were measured in solvents containing D(2)O and H(2)O. In D(2)O or D(2)O/dimethyl sulfoxide (DMSO)-d(6) solvent, signal pattern changes were observed on H12 and H11 as well as 14 methyl protons over time while no changes were observed on H(2)O or H(2)O/DMSO-d(6) solvent. The observed changes in the solvents containing D(2)O were concluded to be caused by the H-D exchange reaction on H12, the process of CH(2)-->CHD-->CD(2). MS spectroscopy also confirmed these H-D exchanges. The kinetics of this reaction were analyzed as the successive reaction, and the mechanism was also proposed.

  1. An in vivo strategy to counteract post-administration anticoagulant activity of azido-Warfarin

    Science.gov (United States)

    Ursuegui, Sylvain; Recher, Marion; Krężel, Wojciech; Wagner, Alain

    2017-05-01

    Drugs, usually long acting and metabolically stable molecules, might be the source of adverse effects triggered by complex drug interactions, anaphylaxis and drug-induced coagulopathy. To circumvent this growing drug safety issue, we herein investigate the opportunity offered by bio-orthogonal chemistry for in vivo drug neutralization. We design a small-molecule anticoagulant drug (Warfarin) containing an azide group that acts as a safety pin. It allows drug deactivation and restoration of physiological coagulation via in vivo click reaction with a suitable cyclooctyne-based neutralizing agent. In this strategy, the new molecule formed by reaction of the drug and the antidote is deprived of biological activity and prone to fast renal clearance. This `Click & Clear' approach lays ground for new strategies in designing drugs with switchable biophysical properties.

  2. Setting priorities in the health care sector – the case of oral anticoagulants in nonvalvular atrial fibrillation in Denmark

    Directory of Open Access Journals (Sweden)

    Poulsen PB

    2017-10-01

    Full Text Available Peter Bo Poulsen,1 Søren Paaske Johnsen,2 Morten Lock Hansen,3 Axel Brandes,4 Steen Husted,5,† Louise Harboe,6 Lars Dybro7 1Pfizer Denmark ApS, Ballerup, 2Department of Clinical Epidemiology, Aarhus University Hospital, 3Department of Cardiology, Zealand University Hospital, Roskilde, 4Department of Cardiology, Odense University Hospital, 5Department of Medicine, Regional Hospital West Jutland, Herning, 6Bristol-Myers Squibb Denmark, Virum, 7Pfizer Denmark, Ballerup, Denmark †Steen Husted passed away on December 28, 2016 Aim: Resources devoted to health care are limited, therefore setting priorities is required. It differs between countries whether decision-making concerning health care technologies focus on broad economic perspectives or whether focus is narrow on single budgets (“silo mentality”. The cost perspective as one part of the full health economic analysis is important for decision-making. With the case of oral anticoagulants in patients with nonvalvular atrial fibrillation (NVAF, the aim is to discuss the implication of the use of different cost perspectives for decision-making and priority setting. Methods: In a cost analysis, the annual average total costs of five oral anticoagulants (warfarin and non-vitamin K oral anticoagulants [NOACs; dabigatran, rivaroxaban, apixaban, and edoxaban] used in daily clinical practice in Denmark for the prevention of stroke in NVAF patients are analyzed. This is done in pairwise comparisons between warfarin and each NOAC based on five potential cost perspectives, from a “drug cost only” perspective up to a “societal” perspective.Results: All comparisons of warfarin and NOACs show that the cost perspective based on all relevant costs, ie, total costs perspective, is essential for the choice of therapy. Focusing on the reimbursement costs of the drugs only, warfarin is the least costly option. However, with the aim of therapy to prevent strokes and limit bleedings, including the

  3. Iterative Development and Evaluation of a Pharmacogenomic-Guided Clinical Decision Support System for Warfarin Dosing.

    Science.gov (United States)

    Melton, Brittany L; Zillich, Alan J; Saleem, Jason; Russ, Alissa L; Tisdale, James E; Overholser, Brian R

    2016-11-23

    Pharmacogenomic-guided dosing has the potential to improve patient outcomes but its implementation has been met with clinical challenges. Our objective was to develop and evaluate a clinical decision support system (CDSS) for pharmacogenomic-guided warfarin dosing designed for physicians and pharmacists. Twelve physicians and pharmacists completed 6 prescribing tasks using simulated patient scenarios in two iterations (development and validation phases) of a newly developed pharmacogenomic-driven CDSS prototype. For each scenario, usability was measured via efficiency, recorded as time to task completion, and participants' perceived satisfaction which were compared using Kruskal-Wallis and Mann Whitney U tests, respectively. Debrief interviews were conducted and qualitatively analyzed. Usability findings from the first (i.e. development) iteration were incorporated into the CDSS design for the second (i.e. validation) iteration. During the CDSS validation iteration, participants took more time to complete tasks with a median (IQR) of 183 (124-247) seconds versus 101 (73.5-197) seconds in the development iteration (p=0.01). This increase in time on task was due to the increase in time spent in the CDSS corresponding to several design changes. Efficiency differences that were observed between pharmacists and physicians in the development iteration were eliminated in the validation iteration. The increased use of the CDSS corresponded to a greater acceptance of CDSS recommended doses in the validation iteration (4% in the first iteration vs. 37.5% in the second iteration, piterations but the qualitative analysis revealed greater trust in the second prototype. A pharmacogenomic-guided CDSS has been developed using warfarin as the test drug. The final CDSS prototype was trusted by prescribers and significantly increased the time using the tool and acceptance of the recommended doses. This study is an important step toward incorporating pharmacogenomics into CDSS design

  4. Warfarin poisoning and vitamin K antagonism in rat and human liver. Design of a system in vitro that mimics the situation in vivo.

    OpenAIRE

    Wallin, R; Martin, L F

    1987-01-01

    The present paper describes a system in vitro that has been developed to mimic vitamin K metabolism and vitamin K function in liver. In this system the two pathways that are known to participate in vitamin K reduction are active and the vitamin K-dependent carboxylase accepts a synthetic pentapeptide as substrate. With this system in vitro the effect of warfarin on both pathways was examined under conditions which simulated a warfarin-poisoned liver. Identical experiments were completed with ...

  5. Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation for the secondary prevention of stroke: a subgroup analysis of J-ROCKET AF.

    Science.gov (United States)

    Tanahashi, Norio; Hori, Masatsugu; Matsumoto, Masayasu; Momomura, Shin-ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iwamoto, Kazuya; Tajiri, Masahiro

    2013-11-01

    The overall analysis of the rivaroxaban versus warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial revealed that rivaroxaban was not inferior to warfarin with respect to the primary safety outcome. In addition, there was a strong trend for a reduction in the rate of stroke/systemic embolism with rivaroxaban compared with warfarin. In this subanalysis of the J-ROCKET AF trial, we investigated the consistency of safety and efficacy profile of rivaroxaban versus warfarin among the subgroups of patients with previous stroke, transient ischemic attack, or non-central nervous system systemic embolism (secondary prevention group) and those without (primary prevention group). Patients in the secondary prevention group were 63.6% of the overall population of J-ROCKET AF. In the secondary prevention group, the rate of the principal safety outcome (% per year) was 17.02 in rivaroxaban-treated patients and 18.26 in warfarin-treated patients (hazard ratio [HR] 0.95; 95% confidence interval [CI] 0.70-1.29), while the rate of the primary efficacy endpoint was 1.66 in rivaroxaban-treated patients and 3.25 in warfarin-treated patients (HR 0.51; 95% CI 0.23-1.14). There were no significant interactions in the principal safety and the primary efficacy endpoints of rivaroxaban compared to warfarin between the primary and secondary prevention groups (P=.090 and .776 for both interactions, respectively). The safety and efficacy profile of rivaroxaban compared with warfarin was consistent among patients in the primary prevention group and those in the secondary prevention group. Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  6. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol.

    Science.gov (United States)

    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

    2008-06-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent.

  7. Promotion or suppression of experimental metastasis of B16 melanoma cells after oral administration of lapachol

    International Nuclear Information System (INIS)

    Maeda, Masayo; Murakami, Manabu; Takegami, Tsutomu; Ota, Takahide

    2008-01-01

    Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] is a vitamin K antagonist with antitumor activity. The effect of lapachol on the experimental metastasis of murine B16BL6 melanoma cells was examined. A single oral administration of a high toxic dose of lapachol (80-100 mg/kg) 6 h before iv injection of tumor cells drastically promoted metastasis. This promotion of metastasis was also observed in T-cell-deficient mice and NK-suppressed mice. In vitro treatment of B16BL6 cells with lapachol promoted metastasis only slightly, indicating that lapachol promotes metastasis primarily by affecting host factors other than T cells and NK cells. A single oral administration of warfarin, the most commonly used vitamin K antagonist, 6 h before iv injection of tumor cells also drastically promoted the metastasis of B16BL6 cells. The promotion of metastasis by lapachol and warfarin was almost completely suppressed by preadministration of vitamin K3, indicating that the promotion of metastasis by lapachol was derived from vitamin K antagonism. Six hours after oral administration of lapachol or warfarin, the protein C level was reduced maximally, without elongation of prothrombin time. These observations suggest that a high toxic dose of lapachol promotes metastasis by inducing a hypercoagulable state as a result of vitamin K-dependent pathway inhibition. On the other hand, serial oral administration of low non-toxic doses of lapachol (5-20 mg/kg) weakly but significantly suppressed metastasis by an unknown mechanism, suggesting the possible use of lapachol as an anti-metastatic agent

  8. Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial.

    Science.gov (United States)

    Piccini, Jonathan P; Stevens, Susanna R; Lokhnygina, Yuliya; Patel, Manesh R; Halperin, Jonathan L; Singer, Daniel E; Hankey, Graeme J; Hacke, Werner; Becker, Richard C; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M; Breithardt, Günter

    2013-05-14

    This study sought to investigate the outcomes following cardioversion or catheter ablation in patients with atrial fibrillation (AF) treated with warfarin or rivaroxaban. There are limited data on outcomes following cardioversion or catheter ablation in AF patients treated with factor Xa inhibitors. We compared the incidence of electrical cardioversion (ECV), pharmacologic cardioversion (PCV), or AF ablation and subsequent outcomes in patients in a post hoc analysis of the ROCKET AF (Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation) trial. Over a median follow-up of 2.1 years, 143 patients underwent ECV, 142 underwent PCV, and 79 underwent catheter ablation. The overall incidence of ECV, PCV, or AF ablation was 1.45 per 100 patient-years (n = 321; 1.44 [n = 161] in the warfarin arm, 1.46 [n = 160] in the rivaroxaban arm). The crude rates of stroke and death increased in the first 30 days after cardioversion or ablation. After adjustment for baseline differences, the long-term incidence of stroke or systemic embolism (hazard ratio [HR]: 1.38; 95% confidence interval [CI]: 0.61 to 3.11), cardiovascular death (HR: 1.57; 95% CI: 0.69 to 3.55), and death from all causes (HR: 1.75; 95% CI: 0.90 to 3.42) were not different before and after cardioversion or AF ablation. Hospitalization increased after cardioversion or AF ablation (HR: 2.01; 95% CI: 1.51 to 2.68), but there was no evidence of a differential effect by randomized treatment (p value for interaction = 0.58). The incidence of stroke or systemic embolism (1.88% vs. 1.86%) and death (1.88% vs. 3.73%) were similar in the rivaroxaban-treated and warfarin-treated groups. Despite an increase in hospitalization, there were no differences in long-term stroke rates or survival following cardioversion or AF ablation. Outcomes were similar in patients treated with rivaroxaban or warfarin

  9. Direct Oral Anticoagulants: An Overview for the Interventional Radiologist

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pradesh, E-mail: pradeshkumar@doctors.org.uk; Ravi, Rajeev, E-mail: rajeev.ravi@aintree.nhs.uk; Sundar, Gaurav, E-mail: gaurav.sundar@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Radiology Department (United Kingdom); Shiach, Caroline, E-mail: caroline.shiach@aintree.nhs.uk [Aintree University Hospitals NHS Foundation Trust, Haematology Department (United Kingdom)

    2017-03-15

    The direct oral anticoagulants (DOACs) have emerged as a good alternative for the treatment of thromboembolic diseases, and their use in clinical practice is increasing rapidly. The DOACs act by blocking the activity of one single step in the coagulation cascade. These drugs act downstream in the common pathway of the coagulation cascade by directly antagonising the action of thrombin or factor Xa. The development of DOACs represents a paradigm shift from the oral vitamin K antagonists such as warfarin. This article aims to describe the properties of the currently available DOACs including pharmacology and dosing. We also address the strategies for periprocedural management and reversal of anticoagulation of patients treated with these agents.

  10. An electrochemical sensor for warfarin determination based on covalent immobilization of quantum dots onto carboxylated multiwalled carbon nanotubes and chitosan composite film modified electrode

    Energy Technology Data Exchange (ETDEWEB)

    Gholivand, Mohammad Bagher, E-mail: mbgholivand2013@gmail.com; Mohammadi-Behzad, Leila

    2015-12-01

    A method is described for the construction of a novel electrochemical warfarin sensor based on covalent immobilization of CdS-quantum dots (CdS-QDs) onto carboxylated multiwalled carbon nanotubes/chitosan (CS) composite film on the surface of a glassy carbon electrode. The CdS-QDs/CS/MWCNTs were characterized by field-emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), Fourier transform infra-red (FTIR) spectroscopy, XRD analysis and electrochemical impedance spectroscopy (EIS). The sensor showed optimum anodic stripping response within 90 s at an accumulation potential of 0.75 V. The modified electrode was used to detect the concentration of warfarin with a wide linear range of 0.05–80 μM and a detection limit (S/N = 3) of 8.5 nM. The proposed sensor has good storage stability, repeatability and reproducibility and was successfully applied for the determination of warfarin in real samples such as urine, serum and milk. - Highlights: • A new sensitive sensor for warfarin determination was developed. • The sensor was constructed based on covalent immobilization of CdS-QDs on the chitosan/MWCNTs/GCE. • The parameters affecting the stripping analysis of warfarin were optimized. • The proposed sensor is used for trace determination of warfarin in urine, serum and milk.

  11. Comparison between Prothrombin Complex Concentrate (PCC) and Fresh Frozen Plasma (FFP) for the Urgent Reversal of Warfarin in Patients with Mechanical Heart Valves in a Tertiary Care Cardiac Center.

    Science.gov (United States)

    Fariborz Farsad, Bahram; Golpira, Reza; Najafi, Hamideh; Totonchi, Ziae; Salajegheh, Shirin; Bakhshandeh, Hooman; Hashemian, Farshad

    2015-01-01

    Fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) reverse oral anticoagulants such as Warfarin. We compared the standard dosage of FFP and PCC in terms of efficacy and safety for patients with mechanical heart valves undergoing interventional procedures while receiving Warfarin. Fifty patients were randomized (25 for each group) with mechanical heart valves [international normalized ratio (INR) >2.5]. FFP dosage was administered based on body weight (10-15 mL/Kg), while PCC dosage was administered based on both body weight and target INR. INR measurements were obtained at different time after PCC and FFP infusion. The mean ± SD of INR pre treatment was not significantly different between the PCC and FFP groups. However, over a 48-hour period following the administration of PCC and FFP, 76% of the patients in the PCC group and only 20% of the patients in the FFP group reached the INR target. Five (20%) patients in the PCC group received an additional dose of PCC, whereas 17 (68%) patients in the FFP group received a further dose of FFP (P=0.001). There was no significant difference between the two groups in Hb and Hct before and during a 48-hour period after PCC and FFP infusion. As regards safety monitoring and adverse drug reaction screening in the FFP group, the INR was high (INR > 2.5) in 86% of the patients. There was no report of hemorrhage in both groups. PCC reverses anticoagulation both effectively and safely while having the advantage of obviating the need to extra doses.

  12. Factors driving the use of warfarin and non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Mu-Mei Hu

    2017-04-01

    Conclusion: Stroke history was associated with anticoagulant use, whereas comorbidities associated with increased risk of bleeding showed the opposite result. Patients with hepatic disease were less likely to use NOACs.

  13. [Randomized Comparison of Two Approaches to Initial Warfarin Dosing: Time in Therapeutic Range of International Normalized Ratio During Hospitalization].

    Science.gov (United States)

    Gordeev, I G; Averkov, O V; Mishchenko, L N; Levchuk, N N; Vechorko, V I

    2017-09-01

    To perform a randomized, open-label comparison of average time in therapeutic range (TTR) of international normalized ratio (INR) using two approaches to initial warfarin dosing during hospitalization: the standard method and the one using individual patient characteristics (clinical algorithm - the studied approach). We randomly assigned 60 patients with different indications for vitamin K antagonist therapy to the studied approach (n=31, intervention group) or to the standard method (n=29, control group). А target INR range for all patients was 2.0 to 3.0. The average TTR and portions of INR values within target range during the whole time of drug dosing turned out to be small. TTR was 22.4% with standard method and 21.4% with clinical algorithm, which was well below desired 60%. The opportunities for achieving target INR in inpatient settings, regardless of warfarin dosing regimen, are limited.

  14. Good quality of oral anticoagulation treatment in general practice using international normalised ratio point of care testing

    DEFF Research Database (Denmark)

    Løkkegaard, Thomas; Pedersen, Tina Heidi; Lind, Bent

    2015-01-01

    INTRODUCTION: Oral anticoagulation treatment (OACT)with warfarin is common in general practice. Increasingly,international normalised ratio (INR) point of care testing(POCT) is being used to manage patients. The aim of thisstudy was to describe and analyse the quality of OACT withwarfarin...... in general practice in the Capital Region of Denmarkusing INR POCT. METHODS: A total of 20 general practices, ten singlehandedand ten group practices using INR POCT, were randomlyselected to participate in the study. Practice organisationand patient characteristics were recorded. INRmeasurements were...... collected retrospectively for a periodof six months. For each patient, time in therapeutic range(TTR) was calculated and correlated with practice and patientcharacteristics using multilevel linear regressionmodels. RESULTS: We identified 447 patients in warfarin treatmentin the 20 practices using POCT...

  15. Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients

    DEFF Research Database (Denmark)

    Li, Xiaoyan; Keshishian, Allison; Hamilton, Melissa

    2018-01-01

    Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbe...... population for which it is being prescribed in United States clinical practice. TRIAL REGISTRATION: Clinicaltrials.Gov Identifier: NCT03087487....

  16. Upper Gastrointestinal System Bleeding Associated with Mallory-Weiss Syndrome in a Patient with Prosthetic Mitral Valve Using Warfarin Sodium

    Directory of Open Access Journals (Sweden)

    Banu Şahin Yıldız

    2013-08-01

    Full Text Available Mallory-Weiss syndrome refers to bleeding from tears in the mucosa at the junction of the stomach and esophagus. Bleeding has been recognised as the major treatment-limiting complication in patients with prosthetic mitral valve using anticoagulant treatment. We report that upper gastrointestinal system bleeding associated with Mallory-Weiss syndrome in patient with prosthetic mitral valve using warfarin sodium.

  17. Predicting warfarin dosage in European–Americans and African–Americans using DNA samples linked to an electronic health record

    Science.gov (United States)

    Ramirez, Andrea H; Shi, Yaping; Schildcrout, Jonathan S; Delaney, Jessica T; Xu, Hua; Oetjens, Matthew T; Zuvich, Rebecca L; Basford, Melissa A; Bowton, Erica; Jiang, Min; Speltz, Peter; Zink, Raquel; Cowan, James; Pulley, Jill M; Ritchie, Marylyn D; Masys, Daniel R; Roden, Dan M; Crawford, Dana C; Denny, Joshua C

    2012-01-01

    Aim Warfarin pharmacogenomic algorithms reduce dosing error, but perform poorly in non-European–Americans. Electronic health record (EHR) systems linked to biobanks may allow for pharmacogenomic analysis, but they have not yet been used for this purpose. Patients & methods We used BioVU, the Vanderbilt EHR-linked DNA repository, to identify European–Americans (n = 1022) and African–Americans (n = 145) on stable warfarin therapy and evaluated the effect of 15 pharmacogenetic variants on stable warfarin dose. Results Associations between variants in VKORC1, CYP2C9 and CYP4F2 with weekly dose were observed in European–Americans as well as additional variants in CYP2C9 and CALU in African–Americans. Compared with traditional 5 mg/day dosing, implementing the US FDA recommendations or the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm reduced error in weekly dose in European–Americans (13.5–12.4 and 9.5 mg/week, respectively) but less so in African–Americans (15.2–15.0 and 13.8 mg/week, respectively). By further incorporating associated variants specific for European–Americans and African–Americans in an expanded algorithm, dose-prediction error reduced to 9.1 mg/week (95% CI: 8.4–9.6) in European–Americans and 12.4 mg/week (95% CI: 10.0–13.2) in African–Americans. The expanded algorithm explained 41 and 53% of dose variation in African–Americans and European–Americans, respectively, compared with 29 and 50%, respectively, for the IWPC algorithm. Implementing these predictions via dispensable pill regimens similarly reduced dosing error. Conclusion These results validate EHR-linked DNA biorepositories as real-world resources for pharmacogenomic validation and discovery. PMID:22329724

  18. Predicting warfarin dosage in European-Americans and African-Americans using DNA samples linked to an electronic health record.

    Science.gov (United States)

    Ramirez, Andrea H; Shi, Yaping; Schildcrout, Jonathan S; Delaney, Jessica T; Xu, Hua; Oetjens, Matthew T; Zuvich, Rebecca L; Basford, Melissa A; Bowton, Erica; Jiang, Min; Speltz, Peter; Zink, Raquel; Cowan, James; Pulley, Jill M; Ritchie, Marylyn D; Masys, Daniel R; Roden, Dan M; Crawford, Dana C; Denny, Joshua C

    2012-03-01

    Warfarin pharmacogenomic algorithms reduce dosing error, but perform poorly in non-European-Americans. Electronic health record (EHR) systems linked to biobanks may allow for pharmacogenomic analysis, but they have not yet been used for this purpose. We used BioVU, the Vanderbilt EHR-linked DNA repository, to identify European-Americans (n = 1022) and African-Americans (n = 145) on stable warfarin therapy and evaluated the effect of 15 pharmacogenetic variants on stable warfarin dose. Associations between variants in VKORC1, CYP2C9 and CYP4F2 with weekly dose were observed in European-Americans as well as additional variants in CYP2C9 and CALU in African-Americans. Compared with traditional 5 mg/day dosing, implementing the US FDA recommendations or the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm reduced error in weekly dose in European-Americans (13.5-12.4 and 9.5 mg/week, respectively) but less so in African-Americans (15.2-15.0 and 13.8 mg/week, respectively). By further incorporating associated variants specific for European-Americans and African-Americans in an expanded algorithm, dose-prediction error reduced to 9.1 mg/week (95% CI: 8.4-9.6) in European-Americans and 12.4 mg/week (95% CI: 10.0-13.2) in African-Americans. The expanded algorithm explained 41 and 53% of dose variation in African-Americans and European-Americans, respectively, compared with 29 and 50%, respectively, for the IWPC algorithm. Implementing these predictions via dispensable pill regimens similarly reduced dosing error. These results validate EHR-linked DNA biorepositories as real-world resources for pharmacogenomic validation and discovery.

  19. Oral histoplasmosis

    Directory of Open Access Journals (Sweden)

    Patil Karthikeya

    2009-01-01

    Full Text Available Histoplasmosis is a systemic fungal disease that takes various clinical forms, among which oral lesions are rare. The disseminated form of the disease that usually occurs in association with Human Immunodeficiency Virus (HIV is one of the AIDS-defining diseases. Isolated oral histoplasmosis, without systemic involvement, with underlying immunosuppression due to AIDS is very rare. We report one such case of isolated oral histoplasmosis in a HIV-infected patient.

  20. Warfarin Safety: A Cross-Sectional Study of the Factors Associated with the Consumption of Medicinal Plants in a Brazilian Anticoagulation Clinic.

    Science.gov (United States)

    Leite, Paula Mendonça; de Freitas, Aline A; Mourão, Aline de O Magalhães; Martins, Maria A P; Castilho, Rachel O

    2018-02-23

    The aim of this study was to analyze factors associated with the consumption of medicinal plants by patients being treated with warfarin in a Brazilian anticoagulation clinic and to study the safety of medicinal plant use in patients on warfarin therapy. The study was performed as an observational cross-sectional analysis. Study participants were outpatients on long-term warfarin therapy for at least 2 months for atrial fibrillation or prosthetic cardiac valves. Interviews were carried out concerning information about the habits of medicinal herb consumption, and logistic regression analysis was performed to identify factors associated with the consumption of herbs. The scientific names of the medicinal plants were identified to search for information on the effects on the hemostasis of the interactions between the medicinal herbs reported and warfarin. The mean age of the 273 patients included was 60.8 years; 58.7% were women. Medicinal plants were used by 67% of the participants. No association between demographic and clinical data and the use of medicinal plants was identified. Patients reported a total of 64 different plants, primarily consumed in the form of tea. The plants were mainly used to treat respiratory tract and central nervous system disorders. About 40% of the plants cited have been reported to potentially interfere with the anticoagulation therapy, principally by potentiating the effects of warfarin, which could, increase the risk of bleeding. The use of medicinal plants was highly common and widespread in patients receiving warfarin as an anticoagulation therapy. Univariate analysis of variables associated with the consumption of herbs showed no statistically significant difference in the consumption of medicinal plants for any of the sociodemographic and clinical data. The medicinal plants that were reportedly consumed by the patients could affect hemostasis. This study reinforces the need for further studies evaluating the habits of patients

  1. Elevated prothrombin time/international normalized ratio associated with concurrent administration of regorafenib and warfarin in a patient with advanced colorectal cancer.

    Science.gov (United States)

    Kitade, Hironori; Hiromasa-Yamasaki, Azusa; Hokkoku, Kengo; Mori, Mitsue; Watanabe, Michio; Nakai, Masuo; Yano, Seiji

    2016-01-01

    Regorafenib and its metabolites may inhibit the activities of several CYP or UDP-glucuronosyltransferase isoforms, including that of CYP2C9. Therefore, pharmacological agents that are CYP2C9 substrates may show elevated circulating levels and enhanced drug efficacy when concurrently used with regorafenib. Previous studies showed that the area under the plasma concentration-time curve of warfarin, which is the substrate for CYP2C9, increased upon co-administration of regorafenib. However, there are no reports indicating that the anticoagulant effects of warfarin increased upon co-administration of regorafenib. We report a case of a 76-year-old man with liver metastasis of colon cancer. He was treated with regorafenib at a dosage of 120 mg daily on days 1 to 21 every 4 weeks as a third-line therapy. He had a history of acute myocardial infarction and had taken 2 mg warfarin daily. Three weeks after the treatment began, PT/INR values markedly increased, although there was no hemorrhage. Administration of regorafenib and warfarin was discontinued, and then PT/INR rapidly decreased. Warfarin administration was restarted (0.5 mg daily) and the dose was increased up to 1.5 mg daily. The patient's PT/INR values exhibited a tendency to increase when concurrently used with regorafenib, the dose of which was reduced to 80 mg daily on days 1 to 14 every 3 weeks at a physician's discretion. The clinical course of this patient suggested that PT/INR might increase during concurrent use of warfarin and regorafenib. Therefore, PT/INR should be periodically monitored during the concurrent use of warfarin and regorafenib.

  2. COMPARISON OF DIRECT COSTS OF DABIGATRAN AND WARFARIN THERAPY IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION DURING PREPARATION FOR ELECTIVE CARDIOVERSION IN THE REAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    L. E. Kuvshinova

    2015-09-01

    Full Text Available Aim. To compare direct medical costs of dabigatran and warfarin therapy in patients with non-valvular atrial fibrillation (NVAF during preparation for elective cardioversion. Material and methods. An open non-randomized study was conducted to evaluate direct medical costs (cost of drug, cost of the international normalized ratio (INR adjust- ment in outpatient clinic, cost of visits to cardiologist. Patients (n=62 with persistent NVAF (AF paroxysm duration > 48 hours were enrolled. All of them requested medical as- sistance and were decided to perform an elective cardioversion. The patients received warfarin (n=32 or dabigatran (n=30. The patients of the both groups were similar in the main clinical characteristics and thromboembolic risk levels according to CHA2DS2-VASc scale.Results. Treatment duration before elective cardioversion was 21±2 and 30.5±4.5 days for dabigatran and warfarin groups, respectively (p<0.05. Average costs of visits to cardiologists were 3,720 and 744 RUB in warfarin and dabigatran groups, respectively (p<0.05, and drug costs were 53.63 and 1,172.01 RUB, respectively (p<0.05. The costs of laboratory INR monitoring were 3,058 RUB in warfarin group. Total costs per patient were 6,831.63 and 1,916.01 RUB in warfarin and dabigatran groups, respectively (p<0.05. Conclusion. In the real clinical practice in patients with NVAF dabigatran antithromboembolic therapy substantially reduces direct medical costs in comparison with warfarin ther- apy during preparation for elective cardioversion. Dabigatran therapy reduces time from the decision of elective cardioversion and antithromboembolic therapy start to car- dioversion performance.

  3. Effect of lipid composition of cationic SUV liposomes on materno-fetal transfer of warfarin across the perfused human term placenta.

    Science.gov (United States)

    Bajoria, R; Sooranna, S; Chatterjee, R

    2013-12-01

    Use of drugs that cross the placenta freely are currently avoided during pregnancy. We investigated whether cationic small unilamellar (SUV) liposomes of different lipid compositions could prevent the transfer and uptake of warfarin across human term placenta. Cationic liposomes encapsulated warfarin was prepared by using lecithin (F-SUV) or sterylamine (S-SUV) with cholesterol and stearylamine. The size distribution, encapsulation efficiency, and stability were determined in blood-based media. The transfer kinetics of free and liposomally encapsulated warfarin were studied in a dually perfused isolated lobule of human term placenta with creatinine. Concentrations of warfarin were measured by fluorimetry. Data are expressed as % of initial dose added and given as mean ± sd. Warfarin crossed the placenta freely (14.9 ± 1.1%). Trans placental transfer of warfarin was significantly reduced by F-SUV (6.4 ± 0.6%; P < 0.001) and S-SUV liposomes (5.0 ± 0.8%; P < 0.001). Placental uptake of F-SUV (6.3 ± 1.7%; P < 0.001) was greater than that of S-SUV liposomes (2.2 ± 0.5%; P < 0.001). Our data suggest that cationic liposomes reduce trans placental transfer of warfarin. If confirmed "in vivo", liposomes might provide an alternative non-invasive method of drug delivery to the mother. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. COMPARISON OF DIRECT COSTS OF DABIGATRAN AND WARFARIN THERAPY IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION DURING PREPARATION FOR ELECTIVE CARDIOVERSION IN THE REAL CLINICAL PRACTICE

    Directory of Open Access Journals (Sweden)

    L. E. Kuvshinova

    2013-01-01

    Full Text Available Aim. To compare direct medical costs of dabigatran and warfarin therapy in patients with non-valvular atrial fibrillation (NVAF during preparation for elective cardioversion. Material and methods. An open non-randomized study was conducted to evaluate direct medical costs (cost of drug, cost of the international normalized ratio (INR adjust- ment in outpatient clinic, cost of visits to cardiologist. Patients (n=62 with persistent NVAF (AF paroxysm duration > 48 hours were enrolled. All of them requested medical as- sistance and were decided to perform an elective cardioversion. The patients received warfarin (n=32 or dabigatran (n=30. The patients of the both groups were similar in the main clinical characteristics and thromboembolic risk levels according to CHA2DS2-VASc scale.Results. Treatment duration before elective cardioversion was 21±2 and 30.5±4.5 days for dabigatran and warfarin groups, respectively (p<0.05. Average costs of visits to cardiologists were 3,720 and 744 RUB in warfarin and dabigatran groups, respectively (p<0.05, and drug costs were 53.63 and 1,172.01 RUB, respectively (p<0.05. The costs of laboratory INR monitoring were 3,058 RUB in warfarin group. Total costs per patient were 6,831.63 and 1,916.01 RUB in warfarin and dabigatran groups, respectively (p<0.05. Conclusion. In the real clinical practice in patients with NVAF dabigatran antithromboembolic therapy substantially reduces direct medical costs in comparison with warfarin ther- apy during preparation for elective cardioversion. Dabigatran therapy reduces time from the decision of elective cardioversion and antithromboembolic therapy start to car- dioversion performance.

  5. Polypharmacy and effects of apixaban versus warfarin in patients with atrial fibrillation: post hoc analysis of the ARISTOTLE trial.

    Science.gov (United States)

    Jaspers Focks, Jeroen; Brouwer, Marc A; Wojdyla, Daniel M; Thomas, Laine; Lopes, Renato D; Washam, Jeffrey B; Lanas, Fernando; Xavier, Denis; Husted, Steen; Wallentin, Lars; Alexander, John H; Granger, Christopher B; Verheugt, Freek W A

    2016-06-15

     To determine whether the treatment effect of apixaban versus warfarin differs with increasing numbers of concomitant drugs used by patients with atrial fibrillation.  Post hoc analysis performed in 2015 of results from ARISTOTLE (apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation)-a multicentre, double blind, double dummy trial that started in 2006 and ended in 2011.  18 201 ARISTOTLE trial participants.  In the ARISTOTLE trial, patients were randomised to either 5 mg apixaban twice daily (n=9120) or warfarin (target international normalised ratio range 2.0-3.0; n=9081). In the post hoc analysis, patients were divided into groups according to the number of concomitant drug treatments used at baseline (0-5, 6-8, ≥9 drugs) with a median follow-up of 1.8 years.  Clinical outcomes and treatment effects of apixaban versus warfarin (adjusted for age, sex, and country).  Each patient used a median of six drugs (interquartile range 5-9); polypharmacy (≥5 drugs) was seen in 13 932 (76.5%) patients. Greater numbers of concomitant drugs were used in older patients, women, and patients in the United States. The number of comorbidities increased across groups of increasing numbers of drugs (0-5, 6-8, ≥9 drugs), as did the proportions of patients treated with drugs that interact with warfarin or apixaban. Mortality also rose significantly with the number of drug treatments (PARISTOTLE trial, three quarters of patients had polypharmacy; this subgroup had an increased comorbidity, more interacting drugs, increased mortality, and higher rates of thromboembolic and bleeding complications. In terms of a potential differential response to anticoagulation therapy in patients with atrial fibrillation and polypharmacy, apixaban was more effective than warfarin, and is at least just as safe.Trial registration ARISTOTLE trial, ClinicalTrials.gov NCT00412984. Published by the BMJ Publishing Group Limited. For permission to use (where

  6. Use of oral anticoagulants in patients with atrial fibrillation and renal dysfunction

    DEFF Research Database (Denmark)

    Potpara, Tatjana S; Ferro, Charles J; Lip, Gregory Y H

    2018-01-01

    development and/or progression. Both conditions are associated with substantial thromboembolic risk, but patients with advanced CKD also exhibit a paradoxical increase in bleeding risk. In the landmark randomized clinical trials that compared non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin...... for the management of patients with AF and severe CKD or end-stage renal disease on dialysis are lacking. Observational cohort studies have reported conflicting results, and the management of these particularly vulnerable patients remains challenging and requires careful assessment of stroke and bleeding risk and...

  7. Should warfarin or aspirin be stopped prior to prostate biopsy? An analysis of bleeding complications related to increasing sample number regimes

    International Nuclear Information System (INIS)

    Chowdhury, R.; Abbas, A.; Idriz, S.; Hoy, A.; Rutherford, E.E.; Smart, J.M.

    2012-01-01

    Aim: To determine whether patients undergoing transrectal ultrasound (TRUS)-guided prostate biopsy with increased sampling numbers are more likely to experience bleeding complications and whether warfarin or low-dose aspirin are independent risk factors. Materials and methods: 930 consecutive patients with suspected prostatic cancer were followed up after biopsy. Warfarin/low-dose aspirin was not stopped prior to the procedure. An eight to 10 sample regime TRUS-guided prostate biopsy was performed and patients were offered a questionnaire to complete 10 days after the procedure, to determine any immediate or delayed bleeding complications. Results: 902 patients returned completed questionnaires. 579 (64.2%) underwent eight core biopsies, 47 (5.2%) underwent nine, and 276 (30.6%) underwent 10. 68 were taking warfarin [mean international normalized ratio (INR) = 2.5], 216 were taking low-dose aspirin, one was taking both, and 617 were taking neither. 27.9% of those on warfarin and 33.8% of those on aspirin experienced haematuria. 37% of those on no blood-thinning medication experienced haematuria. 13.2% of those on warfarin and 14.4% of those on aspirin experienced rectal bleeding. 11.5% of those on no blood-thinning medication experienced rectal bleeding. 7.4% of those on warfarin and 12% of those on aspirin experienced haematospermia. 13.8% of those on neither experienced haematospermia. Regression analysis showed a significant association between increasing sampling number and occurrence of all bleeding complication types. There was no significant association between minor bleeding complications and warfarin use; however, there was a significant association between minor bleeding complications and low-dose aspirin use. There was no severe bleeding complication. Conclusion: There is an increased risk of bleeding complications following TRUS-guided prostate biopsy with increased sampling numbers but these are minor. There is also an increased risk with low

  8. Understanding effect of formulation and manufacturing variables on the critical quality attributes of warfarin sodium product.

    Science.gov (United States)

    Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A

    2015-11-10

    Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50:50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40°C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. Published by Elsevier B.V.

  9. Warfarin poisoning and vitamin K antagonism in rat and human liver. Design of a system in vitro that mimics the situation in vivo.

    Science.gov (United States)

    Wallin, R; Martin, L F

    1987-01-15

    The present paper describes a system in vitro that has been developed to mimic vitamin K metabolism and vitamin K function in liver. In this system the two pathways that are known to participate in vitamin K reduction are active and the vitamin K-dependent carboxylase accepts a synthetic pentapeptide as substrate. With this system in vitro the effect of warfarin on both pathways was examined under conditions which simulated a warfarin-poisoned liver. Identical experiments were completed with rat and human liver. All activities currently associated with vitamin K metabolism and vitamin K function were similar in the rat and human systems. Warfarin neutralized the ability of pathway I (the vitamin K epoxide reductase pathway) to produce reduced and active vitamin K cofactor for the carboxylase. In both the rat and the human system, however, when warfarin was present, reduced vitamin K cofactor was produced by pathway II (the dehydrogenase pathway). The data are consistent with observations in vivo on the effect of vitamin K1 when used as an antidote. This suggests that the system in vitro reflects the mechanism in vivo by which vitamin K1 overcomes warfarin poisoning.

  10. Effect of CYP2C9, VKORC1, CYP4F2 and GGCX genetic variants on warfarin maintenance dose and explicating a new pharmacogenetic algorithm in South Indian population.

    Science.gov (United States)

    Krishna Kumar, Dhakchinamoorthi; Shewade, Deepak Gopal; Loriot, Marie-Anne; Beaune, Philippe; Balachander, Jayaraman; Sai Chandran, B V; Adithan, Chandrasekaran

    2014-01-01

    To determine the influence of genetic polymorphisms on warfarin maintenance dose and to explicate an algorithm using the pharmacogenetic and clinical factors to determine the maintenance and/or starting dose of warfarin in South Indian patients receiving warfarin therapy. Patients receiving stabilized warfarin therapy (n=257) were included in the study. Single nucleotide polymorphisms (SNPs) of CYP2C9 (rs1799853 and rs1057910), VKORC1 (rs9923231, rs7196161, rs2884737, rs9934438, rs8050894, rs2359612 and rs7294), CYP4F2 (rs2108622) and GGCX (rs11676382) were genotyped by the quantitative real time-PCR method. The mean daily maintenance dose of warfarin was found to be 4.7 ± 2.1 mg/day. Patients with the CYP2C9*1/*2, *1/*3 and *2/*3 variant genotypes required a 51.0 (2.8 mg), 60.9 (2.3 mg) and 62.2 % (2.2 mg) lower daily maintenance dose of warfarin, respectively, than those patients with the CYP2C9*1/*1 wild-type genotype (5.2 mg) (pmaintenance dose. Genetic polymorphisms of CYP2C9, VKORC1, CYP4F2 and GGCX are important predictive factors of warfarin maintenance dose, and the developed algorithm will be useful to predict the required maintenance and/or starting warfarin dose in South Indian populations.

  11. Does novel oral anticoagulant improve anticoagulation for non-valvular atrial fibrillation associated stroke: An inpatient registration study in Shanghai

    Directory of Open Access Journals (Sweden)

    Feng-Di Liu

    2015-12-01

    Full Text Available Abstracts: Objective: To summarize the use rate, safety, efficacy of antithrombotics in stroke/transient ischemic attack (TIA prevention, and reasons for not using dabigatran etexilate (DE in Shanghai, China. Methods: Non-valvular atrial fibrillation (NVAF-associated stroke patients were prospectively registered as an electronic database. Use rate of antithrombotics and reasons for not using DE were extracted during follow-up. Patients' baseline characteristics, recurrent ischemic stroke/TIA events and bleeding complications were analyzed. Patients: From April 2012 to August 2014, 110 inpatients with NVAF-associated stroke were studied in our hospital. NVAF was diagnosed by 12-lead electrocardiogram, 24 h Holter and echocardiography. Results: Before introduction of DE (April 2013, use rates of warfarin and antiplatelets were 28.9% (11/38 and 60.5% (23/38 respectively; after that, use rates of warfarin, DE, and antiplatelets were 20.8% (15/72, 12.5% (9/72, and 43.1% (31/72. The DE did not improve use of anticoagulants (P = 0.639. There were 19 (17.3% recurrent ischemic stroke events up to October 2015; two (9.5% in the non-user group, 10 (18.5% in the antiplatelet group, and seven (20.0% in the anticoagulants group (P = 0.570. Furthermore, recurrence rates were similar between the DE group (20.0% and the Warfarin group (20.0%, P = 1.000. The most common reason for not using DE was financial concerns (61.0%, followed by inconvenience to purchase (14.0% and hemorrhage concerns (11.0%. Two patients using warfarin found fecal occult blood so they stopped warfarin and began to use antiplatelet drugs. No bleeding event occurred in the other groups. Only one patient had side effects (dyspepsia and gastroesophageal reflux from DE. Conclusion: The use rate of either DE or warfarin in Shanghai was low; DE had not improved anticoagulation therapy for NVAF patients in Shanghai mainly because DE had not been covered by health insurance. Keywords

  12. Oral Hygiene

    DEFF Research Database (Denmark)

    Sørensen, Marie Toftdahl; Villadsen, Dorte Buxbom

    The aim of the study was to explore how adults with schizo- phrenia describe their lived experiences with oral hygiene. 23 adults with schizophrenia were interviewed within a period of four months in late 2015. Transcriptions of the interviews were analysed using the Reflective Lifeworld Research...... phenomenological approach of Dahlberg, Dahlberg, and Nyström. The essence of the phenomenon, oral hygiene, is described as a challenge: a mixture of ability and assigning priority; a challenge in which significant others, for better or worse, play an important role. We recommend a systematic cooperation between...... health care professionals and adults with schizophrenia in order to improve oral health, well-being and recovery....

  13. Oral Hygiene

    DEFF Research Database (Denmark)

    Villadsen, Dorte Buxbom; Sørensen, Marie Toftdahl

    2017-01-01

    The aim of the study is to explore how adults with schizophrenia describe their lived experiences with oral hygiene. 23 adults with schizophrenia were interviewed within a period of four months in late 2015. Transcriptions of the interviews were analysed using the Reflective Lifeworld Research...... phenomenological approach of Dahlberg, Dahlberg, and Nyström. The essence of the phenomenon, oral hygiene, is described as a challenge: a mixture of ability and assigning priority; a challenge in which significant others, for better or worse, play an important role. We recommend a systematic cooperation between...... health care professionals and adults with schizophrenia in order to improve oral health, well-being and recovery....

  14. Oral Histoplasmosis.

    Science.gov (United States)

    Folk, Gillian A; Nelson, Brenda L

    2017-12-01

    A 44-year-old female presented to her general dentist with the chief complaint of a painful mouth sore of 2 weeks duration. Clinical examination revealed an irregularly shaped ulcer of the buccal and lingual attached gingiva of the anterior mandible. A biopsy was performed and microscopic evaluation revealed histoplasmosis. Histoplasmosis, caused by Histoplasma capsulate, is the most common fungal infection in the United States. Oral lesions of histoplasmosis are generally associated with the disseminated form of histoplasmosis and may present as a fungating or ulcerative lesion of the oral mucosa. The histologic findings and differential diagnosis for oral histoplasmosis are discussed.

  15. Effect of Genotype-Guided Warfarin Dosing on Clinical Events and Anticoagulation Control Among Patients Undergoing Hip or Knee Arthroplasty: The GIFT Randomized Clinical Trial.

    Science.gov (United States)

    Gage, Brian F; Bass, Anne R; Lin, Hannah; Woller, Scott C; Stevens, Scott M; Al-Hammadi, Noor; Li, Juan; Rodríguez, Tomás; Miller, J Philip; McMillin, Gwendolyn A; Pendleton, Robert C; Jaffer, Amir K; King, Cristi R; Whipple, Brandi DeVore; Porche-Sorbet, Rhonda; Napoli, Lynnae; Merritt, Kerri; Thompson, Anna M; Hyun, Gina; Anderson, Jeffrey L; Hollomon, Wesley; Barrack, Robert L; Nunley, Ryan M; Moskowitz, Gerard; Dávila-Román, Victor; Eby, Charles S

    2017-09-26

    Warfarin use accounts for more medication-related emergency department visits among older patients than any other drug. Whether genotype-guided warfarin dosing can prevent these adverse events is unknown. To determine whether genotype-guided dosing improves the safety of warfarin initiation. The randomized clinical Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis included patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty and was conducted at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Patients were genotyped for the following polymorphisms: VKORC1-1639G>A, CYP2C9*2, CYP2C9*3, and CYP4F2 V433M. In a 2 × 2 factorial design, patients were randomized to genotype-guided (n = 831) or clinically guided (n = 819) warfarin dosing on days 1 through 11 of therapy and to a target international normalized ratio (INR) of either 1.8 or 2.5. The recommended doses of warfarin were open label, but the patients and clinicians were blinded to study group assignment. The primary end point was the composite of major bleeding, INR of 4 or greater, venous thromboembolism, or death. Patients underwent a screening lower-extremity duplex ultrasound approximately 1 month after arthroplasty. Among 1650 randomized patients (mean age, 72.1 years [SD, 5.4 years]; 63.6% women; 91.0% white), 1597 (96.8%) received at least 1 dose of warfarin therapy and completed the trial (n = 808 in genotype-guided group vs n = 789 in clinically guided group). A total of 87 patients (10.8%) in the genotype-guided group vs 116 patients (14.7%) in the clinically guided warfarin dosing group met at least 1 of the end points (absolute difference, 3.9% [95% CI, 0.7%-7.2%], P = .02; relative rate [RR], 0.73 [95% CI, 0.56-0.95]). The numbers of individual events in the genotype-guided group vs the clinically guided group were 2 vs 8 for major bleeding (RR, 0.24; 95% CI, 0

  16. Herpes - oral

    Science.gov (United States)

    ... virus type 2 (HSV-2) most often causes genital herpes . However, sometimes HSV-2 is spread to the ... the virus to the genitals. Both oral and genital herpes viruses can sometimes be spread, even when you ...

  17. Design and rationale for the WARFA trial: a randomized controlled cross-over trial testing the therapeutic equivalence of branded and generic warfarin in atrial fibrillation patients in Brazil.

    Science.gov (United States)

    Freitas, Carolina Gomes; Walsh, Michael; Atallah, Álvaro Nagib

    2017-06-07

    Warfarin is a commonly used anticoagulant. Whether a given dose of the different formulations of Brazilian warfarin will result in the same effect on the international normalized ratio (INR) is uncertain. The aim of the WARFA trial is to determine whether the branded and two generic warfarins available in Brazil differ in their effect on the INR. WARFA is a cross-over RCT comparing three warfarins. The formulations tested are the branded Marevan® (Uniao Quimica/Farmoquimica) and two generic warfarin (manufactured respectively by Uniao Quimica Farmaceutica Nacional and Laboratorio Teuto Brasileiro). All of them were manufactured in Brazil, are available in all settings of the Brazilian healthcare system and were purchased from retail drugstores. Eligible participants had atrial fibrillation or flutter, had been using warfarin for at least 2 months with a therapeutic range of 2.0-3.0 and had low variability in INR results during the 1st period of the trial. Our primary outcome, for which we have an equality hypothesis, is the difference between warfarins in the mean absolute difference between two INR results, obtained after three and 4 weeks with each drug. Our secondary outcomes, that will be tested for inequality (except for the mean INR, which will be tested for equality), include the difference in the warfarin dose, and time in therapeutic range. Clinical events and adherence were also recorded and will be reported. To our knowledge, WARFA will be the first comparison of the more readily applicable INR results between branded and generic warfarins in Brazil. WARFA is important because warfarins are commonly switched between in the course of a chronic treatment in Brazil. Final results of WARFA are expected in May 2017. ClinicalTrials.gov NCT02017197 . Registered 11 December 2013.

  18. Chemostimuli for guanylyl cyclase-D-expressing olfactory sensory neurons promote the acquisition of preferences for foods adulterated with the rodenticide warfarin

    Directory of Open Access Journals (Sweden)

    Kevin Robert Kelliher

    2015-07-01

    Full Text Available Many animals have the ability to acquire food preferences from conspecifics via social signals. For example, the coincident detection of a food odor by canonical olfactory sensory neurons (OSNs and agonists of the specialized OSNs expressing the receptor guanylyl cyclase GC-D (GC-D+ OSNs will promote a preference in recipient rodents for similarly odored foods. It has been hypothesized that these preferences are acquired and maintained regardless of the palatability or quality of the food. We assessed whether mice could acquire and maintain preferences for food that had been adulterated with the anticoagulant rodenticide warfarin. After olfactory investigation of a saline droplet containing either cocoa (2%, w/w or cinnamon (1%, w/w along with a GC-D+ OSN-specific chemostimulus (either of the guanylin-family peptides uroguanylin and guanylin; 1–50 nM, C57BL/6J mice exhibited robust preferences for unadulterated food containing the demonstrated odor. The peptide-dependent preference was observed even when the food contained warfarin (0.025% w/w. Repeated ingestion of warfarin-containing food over four days did not disrupt the preference, even though mice were not re-exposed to the peptide stimulus. Surprisingly, mice continued to prefer warfarin-adulterated food containing the demonstrated odor when presented with a choice of warfarin-free food containing a novel odor. Our results indicate that olfactory-mediated food preferences can be acquired and maintained for warfarin-containing foods and suggest that guanylin peptides may be effective stimuli for promoting the ingestion of foods or other edibles with low palatability or potential toxicity.

  19. Rivaroxaban versus warfarin in Japanese patients with non-valvular atrial fibrillation in relation to hypertension: a subgroup analysis of the J-ROCKET AF trial.

    Science.gov (United States)

    Matsumoto, Masayasu; Hori, Masatsugu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-05-01

    The majority of the patients enrolled in the rivaroxaban vs. warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial had hypertension. In this subgroup analysis, we investigated differences in the safety and efficacy of rivaroxaban and warfarin in subjects with and without hypertension. The baseline blood pressure (BP) measurements of patients with hypertension in the rivaroxaban and warfarin groups were 130/77 mm Hg and 131/77 mm Hg, respectively, whereas those of patients without hypertension were 123/74 mm Hg and 124/73 mm Hg, respectively. The incidence rates of the principal safety outcomes in the rivaroxaban and warfarin groups were 18.39% per year and 16.81% per year, respectively, among patients with baseline hypertension (hazard ratio (HR): 1.10; 95% confidence interval (CI): 0.84-1.45) and 16.71% per year and 15.00% per year, respectively, among patients without hypertension at baseline (HR: 1.14; 95% CI: 0.66-1.97), indicating no significant interaction (P=0.933). The incidence rates of the primary efficacy endpoints in the rivaroxaban group and the warfarin group were 0.54% per year and 2.24% per year, respectively, in patients without baseline hypertension (HR: 0.25; 95% CI: 0.03-2.25), and 1.45% per year and 2.71% per year, respectively, in patients with baseline hypertension (HR: 0.54; 95% CI: 0.25-1.16), indicating no significant interaction (P=0.509). In conclusion, the safety and efficacy profile of rivaroxaban was similar to that of warfarin, independent of baseline hypertensive status.

  20. Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation in relation to the CHADS2 score: a subgroup analysis of the J-ROCKET AF trial.

    Science.gov (United States)

    Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Uchiyama, Shinichiro; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-02-01

    Results from a trial of rivaroxaban versus warfarin in 1280 Japanese patients with atrial fibrillation (J-ROCKET AF) revealed that rivaroxaban was noninferior to warfarin with respect to the principal safety outcome. In this subanalysis, we investigated the safety and efficacy of rivaroxaban and warfarin in relation to patients' CHADS2 scores. The mean CHADS2 score was 3.25, and the most frequent scores were 3 and 4. No statistically significant interactions were observed between principal safety outcome event rates and CHADS2 scores with respect to treatment groups (P value for interaction = .700). Irrespective of stratification into moderate- and high-risk groups based on CHADS2 scores of 2 and 3 or more, respectively, no differences in principal safety outcome event rates were observed between rivaroxaban- and warfarin-treated patients (moderate-risk group: hazard ratio [HR], 1.06; 95% confidence interval [CI], .58-1.95; high-risk group: HR, 1.11; 95% CI, .86-1.45; P value for interaction = .488). The primary efficacy end point rate in the rivaroxaban-treated group was numerically lower than in the warfarin-treated group, regardless of risk group stratification (moderate-risk group: HR, .46; 95% CI, .09-2.37; high-risk group: HR, .49; 95% CI, .22-1.11; P value for interaction = .935). This subanalysis indicated that the safety and efficacy of rivaroxaban compared with warfarin were similar, regardless of CHADS2 score. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  1. [Oral contraceptives].

    Science.gov (United States)

    Rozenbaum, H

    1976-10-23

    The author presents an alphabetical list of oral contraceptives. To classify the commercial names of oral contraceptives all over the world is practically impossible for the following reasons: some agents are discontinued without the medical profession being aware of it; the same product can have various names depending on the country and the laboratory. Some products exist in different forms (21 pills including 7 inactive tablets). Finally, some laboratories change the posology of a product without changing its name.

  2. Disparities in Oral Health

    Science.gov (United States)

    ... 2020: Oral Health Objectives Site Map Disparities in Oral Health Recommend on Facebook Tweet Share Compartir Oral health ... to get and keep dental insurance. Disparities in Oral Health Some of the oral health disparities that exist ...

  3. High homocysteine and low folate plasma concentrations are associated with cardiovascular events but not bleeding during warfarin treatment.

    Science.gov (United States)

    Lind, Marcus; Jansson, Jan-Håkan; Nilsson, Torbjörn K; Johansson, Lars

    2016-12-01

    Previous studies have shown that homocysteine and folate levels in plasma are associated with risk for cardiovascular events and mortality. The aim of this study was to investigate if plasma concentrations of total homocysteine and folate can predict major bleeding, cardiovascular events, and all-cause mortality in patients being treated with warfarin. In a longitudinal cohort study, 719 patients who were taking warfarin were followed for 3001 treatment years. The following were recorded and classified: major bleeding; cardiovascular events including stroke, arterial emboli, and myocardial infarction (MI); and mortality. Blood samples collected at baseline were analysed for plasma homocysteine and folate levels. After adjustment for age, C-reactive protein, and creatinine, high homocysteine levels were associated with cardiovascular events [hazard ratio (HR) 1.23 per standard deviation (SD); 95% confidence interval (CI): 1.03-1.47], MI (HR 1.38 per SD; 95% CI: 1.03-1.85), and all-cause mortality (HR 1.41 per SD; 95% CI: 1.19-1.68). The highest tertile of folate compared to the lowest tertile was associated with decreased risk for both cardiovascular events (HR 0.64; 95% CI: 0.43-0.91) and MI (HR 0.45; 95% CI: 0.21-0.97). There was no association between major bleeding and homocysteine or folate levels. In patients receiving warfarin treatment, high homocysteine and low folate plasma concentrations are associated with increased risk for cardiovascular events but not major bleeding. For homocysteine levels, there is also an association with all-cause mortality.

  4. Cost-effectiveness of non-vitamin K antagonist oral anticoagulants for atrial fibrillation in Portugal.

    Science.gov (United States)

    Costa, João; Fiorentino, Francesca; Caldeira, Daniel; Inês, Mónica; Lopes Pereira, Catarina; Pinheiro, Luís; Vaz-Carneiro, António; Borges, Margarida; Gouveia, Miguel

    2015-12-01

    Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  5. Improving the management of warfarin in aged-care facilities utilising innovative technology: a proof-of-concept study.

    Science.gov (United States)

    Bereznicki, Luke R E; Jackson, Shane L; Kromdijk, Wiete; Gee, Peter; Fitzmaurice, Kimbra; Bereznicki, Bonnie J; Peterson, Gregory M

    2014-02-01

    In aged-care facilities (ACFs) monitoring of warfarin can be logistically challenging and International Normalised Ratio (INR control) is often suboptimal. We aimed to determine whether an integrated information and communications technology system and the use of point-of-care (POC) monitors by nursing staff could improve the INR control of aged-care facility residents who take warfarin. Nursing staff identified residents who were prescribed warfarin in participating ACFs. A computer program (MedePOC) was developed to store and transmit INR results from the ACFs to general practitioners (GPs) for dosage adjustment. Nursing staff received training in the use of the CoaguChek XS point-of-care INR monitor and the MedePOC software. Following a run-in phase, eligible patients were monitored weekly for up to 12 weeks. The primary outcome was the change in the time in therapeutic range (TTR) in the intervention phase compared to the TTR in the 12 months preceding the study. All GPs, nursing staff and patients were surveyed for their experiences and opinions of the project. Twenty-four patients and 19 GPs completed the trial across six ACFs. The mean TTR for all patients improved non-significantly from 58.9 to 60.6% (P=0.79) and the proportion of INR tests in range improved non-significantly from 57.1 to 64.1% (P=0.21). The mean TTR improved in 14 patients (58%) and in these patients the mean absolute improvement in TTR was 23.1%. A post hoc analysis of the INR data using modified therapeutic INR ranges to reflect the dosage adjustment practices of GPs suggested that the intervention did lead to improved INR control. The MedePOC program and POC monitoring was well received by nursing staff. Weekly POC INR monitoring conducted in ACFs and electronic communication of the results and warfarin doses resulted in non-significant improvements in INR control in a small cohort of elderly residents. Further research involving modification to the communication strategy and a longer

  6. Non-traumatic ocular and periocular hemorrhages in a hypertensive patient under continuous ambulatory peritoneal dialysis and warfarin therapy.

    Science.gov (United States)

    Yen, Hung-Wen; Lau, Ling-Ing; Yang, Wu-Chang; Lin, Pei-Yu; Shen, Chia-Lin; Hu, Fen-Hsiang; Lin, Chih-Ching

    2014-01-01

    We herein present the first reported case of severe proptosis caused by ocular and periocular hemorrhages in a continuous ambulatory peritoneal dilaysis patient without previous history of trauma. The bleeding tendency caused by uremia and the use of warfarin during uncontrolled high blood pressure were most likely responsible for her ocular and periocular hemorrhages. Appropriate control of blood pressure and adequate self-care education are important for the prevention and treatment of any bleeding complications in uremic patients receiving both maintenance anticoagulation therapy and peritoneal dialysis.

  7. Comparison of 3-Factor Versus 4-Factor Prothrombin Complex Concentrate With Regard to Warfarin Reversal, Blood Product Use, and Costs.

    Science.gov (United States)

    DeAngelo, Jessica; Jarrell, Daniel; Cosgrove, Richard; Camamo, James; Edwards, Christopher; Patanwala, Asad E

    2017-07-26

    Prothrombin complex concentrates (PCCs) are drug products containing varying amounts of vitamin K-dependent coagulation factors II, VII, IX, and X. The evidence comparing 3-factor PCC (3-PCC) versus 4-factor PCC (4-PCC) for warfarin reversal is conflicting. It has been hypothesized that 3-PCC may be less effective than 4-PCC because of relatively lower factor VII content. The primary objective of this study was to compare international normalized ratio (INR) reversal between 3-PCC and 4-factor PCC (4-PCC) in warfarin-treated patients. The secondary objectives include comparing blood product use, total reversal costs, and cost-effectiveness between the groups. This was a retrospective cohort study conducted in 2 affiliated, academic institutions in the United States. Consecutive adult patients who received 3-PCC or 4-PCC for warfarin reversal were included. The primary outcome was adequate INR reversal defined as a final INR ≤1.5. Secondary outcomes were the utilization of plasma, red blood cells and platelets, reversal costs, and the cost-effectiveness ratio. There were 89 patients who were included in the overall cohort (3-PCC = 57, 4-PCC = 32). Adequate INR reversal occurred less commonly with 3-PCC (45.6%) compared with 4-PCC (87.5%) (P < 0.001). There was no significant difference in the proportion of patients who received plasma (32% vs. 28%, P = 0.813), red blood cells (37% vs. 47%, P = 0.377), or platelets (16% vs. 28%, P = 0.180) between the 3-PCC and 4-PCC groups, respectively. The median reversal cost of 3-PCC ($3663) was lower than 4-PCC ($5105) (P = 0.001). The cost-effective ratio favored 4-PCC ($5105/87.5% = $5834) compared with 3-PCC ($3663/45.6% = $8033). Four-PCC was more effective than 3-PCC with regard to INR reversal in patients taking warfarin, but blood product use was similar. Although 4-PCC is associated with increased reversal costs, it may be cost-effective in terms of INR reversal.

  8. Implementing Algorithm-Guided Warfarin Dosing in an Ethnically Diverse Patient Population Using Electronic Health Records and Preemptive CYP2C9 and VKORC1 Genetic Testing.

    Science.gov (United States)

    Obeng, A Owusu; Kaszemacher, T; Abul-Husn, N S; Gottesman, O; Vega, A; Waite, E; Myers, K; Cho, J; Bottinger, E P; Ellis, S B; Scott, S A

    2016-11-01

    Implementation of pharmacogenetic-guided warfarin dosing has been hindered by inconsistent results from reported clinical trials and a lack of available algorithms that include alleles prevalent in non-white populations. However, current evidence indicates that algorithm-guided dosing is more accurate than empirical dosing. To facilitate multiethnic algorithm-guided warfarin dosing using preemptive genetic testing, we developed a strategy that accounts for the complexity of race and leverages electronic health records for algorithm variables and deploying point-of-care dose recommendations. © 2016 American Society for Clinical Pharmacology and Therapeutics.

  9. Organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin on chalcones: Synthesis, NMR and single-crystal X-ray diffraction studies of novel warfarin analogues

    Science.gov (United States)

    Talhi, Oualid; Fernandes, José A.; Pinto, Diana C. G. A.; Almeida Paz, Filipe A.; Silva, Artur M. S.

    2015-08-01

    The synthesis of a new series of warfarin analogues by convenient organobase catalyzed 1,4-conjugate addition of 4-hydroxycoumarin to chalcone derivatives is described. 1H NMR spectroscopy evidenced the presence of a predominant acyclic open-form together with the cyclic hemiketal tautomers of the resulting Michael adducts. The acyclic open-form has been unequivocally proved by single-crystal X-ray diffraction analysis. The use of the B ring ortho-hydroxychalcone synthons in this reaction has led to a diastereoselective synthesis of warfarin bicyclo[3.3.1]nonane ketal derivatives.

  10. Real world usage of PCC to "rapidly" correct warfarin induced coagulopathy.

    Science.gov (United States)

    Toth, Peter; van Veen, Joost Jair; Robinson, Kate; Maclean, Rhona Murray; Hampton, Kingsley Kevin; Laidlaw, Stuart; Makris, Michael

    2013-10-01

    Life threatening bleeding and emergency procedures in patients on vitamin K antagonists are indications for urgent reversal with prothrombin complex concentrate and vitamin K. Rapid reversal in these situations is emphasized in the literature and guidelines, but only very limited information is available on its real life use, especially on the timing of treatment in relation to presentation. We retrospectively audited emergency warfarin reversal in 131 consecutive patients. We studied the indication, use of vitamin K, time between presentation and administration of vitamin K and PCC, effectiveness in INR reduction and clinical outcome. The median PCC dose was 26.8 IU/kg. The median INR was reduced from 3.1 to 1.2. Vitamin K (5 mg) was given in 91.6% of evaluable patients. We found significant delays in administration of PCC and vitamin K. The median time between presentation and administration of vitamin K/PCC was 3.6 and 5.2 hours respectively. The times in intracranial haemorrhage were 2.7 and 3.0 hours and in emergency procedures 17.4 and 15.9 hours respectively. Mortality related to bleeding was 7.6% overall but in patients with intracranial haemorrhage 22.8%. The thrombotic rate within 7 days of reversal was 1.5%. The local protocol for reversal with PCC and vitamin K was adhered to well but the delay in pre-procedural patients, suggests that intravenous vitamin K alone may be sufficient in many cases and PCC administration can be avoided by better planning. Intracranial haemorrhage in warfarinised patients carries a high mortality. Treatment delays should be avoided by making PCC stocks available within emergency departments, simple dosing structures independent of INR and administering PCC without waiting for INR and CT scan results in those with strong suspicion of intracranial haemorrhage and clear trauma. Future reports and studies should always include the time from presentation to PCC treatment.

  11. [Management of new oral anticoagulants in gastrointestinal bleeding and endoscopy].

    Science.gov (United States)

    del Molino, Fátima; Gonzalez, Isabel; Saperas, Esteve

    2015-10-01

    New oral direct anticoagulants agents are alternatives to warfarin for long-term anticoagulation in a growing number of patients that require long-term anticoagulation for atrial fibrillation, deep venous thrombosis and pulmonary embolism. These new agents with predictable pharmacokinetic and pharmacodynamics profiles offer a favorable global safety profile, but increased gastrointestinal bleeding compared to the vitamin K antagonists. Many gastroenterologists are unfamiliar and may be wary of these newer drugs, since Clinical experience is limited and no specific antidote is available to reverse their anticoagulant effect. In this article the risk of these new agents and, how to manage these agents in both the presence of acute gastrointestinal bleeding and in patients undergoing endoscopic procedures is reviewed. Copyright © 2014 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  12. A randomised controlled trial comparing weight adjusted dose ...

    African Journals Online (AJOL)

    A prophylactic phenylephrine infusion combined with a fluid co-load is proven to be an effective and safe method of maintaining maternal hemodynamic stability. ... for non-urgent caesarean section under spinal anaesthesia were randomized into 2 groups; control group and intervention group using a computer generated ...

  13. Cost reduction in abdominal CT by weight-adjusted dose

    International Nuclear Information System (INIS)

    Arana, Estanislao; Marti-Bonmati, Luis; Tobarra, Eva; Sierra, Consuelo

    2009-01-01

    Aim: To analyze the influence of contrast dose adjusted by weight vs. fixed contrast dose in the attenuation and cost of abdominal computed tomography (CT). Materials and methods: A randomised, consecutive, parallel group study was conducted in 151 patients (74 men and 77 women, age range 22-67 years), studied with the same CT helical protocol. A dose at 1.75 ml/kg was administered in 101 patients while 50 patients had a fixed dose of 120 ml of same non-ionic contrast material (320 mg/ml). Mean enhancements were measured at right hepatic lobe, superior abdominal aorta and inferior cava vein. Statistical analysis was weight-stratified ( 81 kg). Results: Aortic attenuation was significantly superior (p 61 kg in dose-adjusted group, presented higher hepatic attenuation, being statistically significant in those >81 kg (p 80 kg, there was an over cost of Euro 10.7 per patient. Conclusions: An injection volume of 1.75 ml/kg offers an optimal diagnostic quality with a global savings of Euro 1.34 per patient.

  14. Cost reduction in abdominal CT by weight-adjusted dose.

    Science.gov (United States)

    Arana, Estanislao; Martí-Bonmatí, Luis; Tobarra, Eva; Sierra, Consuelo

    2009-06-01

    To analyze the influence of contrast dose adjusted by weight vs. fixed contrast dose in the attenuation and cost of abdominal computed tomography (CT). A randomised, consecutive, parallel group study was conducted in 151 patients (74 men and 77 women, age range 22-67 years), studied with the same CT helical protocol. A dose at 1.75 ml/kg was administered in 101 patients while 50 patients had a fixed dose of 120 ml of same non-ionic contrast material (320 mg/ml). Mean enhancements were measured at right hepatic lobe, superior abdominal aorta and inferior cava vein. Statistical analysis was weight-stratified (81 kg). Aortic attenuation was significantly superior (p61 kg in dose-adjusted group, presented higher hepatic attenuation, being statistically significant in those >81 kg (p80 kg, there was an over cost of euro 10.7 per patient. An injection volume of 1.75 ml/kg offers an optimal diagnostic quality with a global savings of euro 1.34 per patient.

  15. Oral anticoagulant discontinuation in patients with nonvalvular atrial fibrillation.

    Science.gov (United States)

    Kachroo, Sumesh; Hamilton, Melissa; Liu, Xianchen; Pan, Xianying; Brixner, Diana; Marrouche, Nassir; Biskupiak, Joseph

    2016-01-01

    To identify factors associated with all-cause discontinuation (patient discontinued on their own or physician discontinuation) of oral anticoagulants (OACs) among nonvalvular atrial fibrillation (NVAF) patients. Retrospective cohort study. We analyzed the MarketScan claims database from October 2009 to July 2012. Adult patients were eligible if they newly initiated an OAC in the study period, had an atrial fibrillation diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 427.31 or 472.32), and had at least 6 months of continuous enrollment after OAC initiation. Multivariable Cox proportional hazards regression was used to assess factors associated with discontinuation. Adjusted hazard ratios (HRs) and 95% CIs were reported. Among 12,129 eligible patients, 8143 (67.1%) initiated warfarin and 3986 (32.9%) initiated direct oral anticoagulants (DOACs). Overall, 47.3% of patients independently discontinued during follow-up (mean number of days of follow-up = 416.6 [SD ± 141.7]) with mean time to discontinuation of 120 days (SD ± 114.7). Patients significantly less likely to discontinue included those taking DOACs versus warfarin (HR, 0.91; 95% CI, 0.86-0.97), older patients (≥65 years vs 18 to 34 years) (HR, 0.32; 95% CI, 0.24-0.43), those with diabetes (HR, 0.84; 95% CI, 0.77-0.90), those with prior stroke/transient ischemic attack (HR, 0.65; 95% CI, 0.56-0.75), those with prior pulmonary embolism (HR, 0.71; 95% CI, 0.58-0.88), and those with congestive heart failure (HR, 0.80; 95% CI, 0.74-0.87). Patients with prior bleeding events were significantly more likely to independently discontinue (HR, 1.20; 95% CI, 1.08-1.34). The risk of independent discontinuation of OAC treatment among NVAF patients was high. Patients on DOACs compared with warfarin and those with several comorbid conditions had significantly lower risk of discontinuation, while those with prior bleeding were more likely to discontinue.

  16. Vitamina K: metabolismo, fontes e interação com o anticoagulante varfarina Vitamin K: metabolism, sources and interaction with the anticoagulant warfarin

    Directory of Open Access Journals (Sweden)

    Karin Klack

    2006-12-01

    phylloquinone. Dark green leafy vegetables, usually mixed with oils, nuts and some fruits, including kiwi, avocado, grapes, plums, and figs are rich sources of vitamin K, whereas cereals, grains, breads, and dairy products present low amounts. The daily ingestion of approximately 1µg/kg body-weight is considered safe, even with concomitant oral anticoagulant use, since stable vitamin concentration contributes to anticoagulant efficacy. The most commonly used oral anticoagulant formation is warfarin, that is indicated to both prophylactic and therapeutic tromboembolic phenomena. It is currently monitored by assessing prothrombin time, after adjusting for the international normalized ratio (INR. Usually, the oral dose is adjusted to set the INR in the range of 2 - 3, in order to achieve the treatment objective. The anticoagulating efficacy is influenced by a variety of clinical factors, such as weight gain, diarrhoea, vomiting, age under 40, and excessive vitamin K daily consumption.

  17. Assessment of Oral Anticoagulant Use in Residents of Long-Term Care Homes: Evidence for Contemporary Suboptimal Use.

    Science.gov (United States)

    Rojas-Fernandez, Carlos H; Goh, Joslin; Hartwick, Jennifer; Auber, Ruth; Zarrin, Aein; Warkentin, Melissa; Hudani, Zain

    2017-12-01

    To describe the quality of warfarin use in residents of long-term care facilities and investigate potential predictors oral anticoagulant use. Retrospective chart review (August 2013 to September 2014). Thirteen long-term care (LTC) and assisted living facilities (ALF). Residents from LTC or ALF settings who ( a) received warfarin or direct-acting oral anticoagulants (DOACs) and ( b) residents with a valid indication for oral anticoagulants such as atrial fibrillation, venous thromboembolism, but were not receiving these drugs. Time in therapeutic international normalized ratio (INR) range (TTR). A total of 563 residents (70% female) with an average age of 85 years were identified. Participants had an average of 7.5 comorbidities and 9 medications. A total of 391 (69%) residents with indications for OACs were receiving such medications. Indications were atrial fibrillation (63%), venous or pulmonary embolism (16%), cardiac valves (0.4%); 26% did not have documented indications. Warfarin and DOACs were prescribed for 213 (38%) and 178 (32%) respectively, and 172 (31%) received no OACs The TTR ranged from 56%-75% (mean 63%). The frequency of INR determinations ranged from every 7 to 20 days, (mean 13 days) with no apparent relationship between frequency of testing and TTR. The TTR was higher (63.8%) than literature average (50%), but remains suboptimal given expected benefits of TTRs >75% versus TTRs circa 60%. Documentation of indications for OACs needs improvement, and it is possible that OACs are underused. Further work is necessary to understand how OAC use may be optimized in these facilities.

  18. Evaluation of the interactions between human serum albumin (HSA and warfarin or diflunisal by using molecular fluorescence using two approaches

    Directory of Open Access Journals (Sweden)

    Susana Amézqueta

    2018-03-01

    Full Text Available Serum albumin is the main drug transporter of the bloodstream and contains two main binding sites:  Sudlow I or acidic drug binding site, and Sudlow II or benzodiazepine binding site. Warfarin, a well-known anticoagulant drug commonly used in the prevention of thrombosis and thromboembolism, binds to Sudlow I site, whereas non-steroidal antiinflammatory drugs (NSAIDs such as diflunisal bind preferentially to Sudlow II site.  Albumin is a fluorophore that modifies its fluorescence (quenching or enhancement effect when it is bound to a drug. The application of the double logarithm Stern-Volmer equation allows the calculation of the stoichiometry and the binding constant of the process. This procedure does not consider the possible interferences coming from the fluorescence of the drug though. Another strategy to evaluate the binding constants is to consider the whole spectrum, taking into account all the possible species in equilibrium; in this case we have used an extended version of the STAR program, which can deal with 300 spectra, each containing up to 300 data points. The aim of this work is to compare both approaches to evaluate the interaction between warfarin (Sudlow I and diflunisal (Sudlow II and HSA: the double logarithm Stern-Volmer equation and the STAR program.

  19. Patients' time in therapeutic range on warfarin among US patients with atrial fibrillation: Results from ORBIT-AF registry.

    Science.gov (United States)

    Pokorney, Sean D; Simon, DaJuanicia N; Thomas, Laine; Fonarow, Gregg C; Kowey, Peter R; Chang, Paul; Singer, Daniel E; Ansell, Jack; Blanco, Rosalia G; Gersh, Bernard; Mahaffey, Kenneth W; Hylek, Elaine M; Go, Alan S; Piccini, Jonathan P; Peterson, Eric D

    2015-07-01

    Time in therapeutic range (TTR) of international normalized ratio (INR) of 2.0 to 3.0 is important for the safety and effectiveness of warfarin anticoagulation. There are few data on TTR among patients with atrial fibrillation (AF) in community-based clinical practice. Using the US Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), we examined TTR (using a modified Rosendaal method) among 5,210 patients with AF on warfarin and treated at 155 sites. Patients were grouped into quartiles based on TTR data. Multivariable logistic regression modeling with generalized estimating equations was used to determine patient and provider factors associated with the lowest (worst) TTR. Overall, 59% of the measured INR values were between 2.0 and 3.0, with an overall mean and median TTR of 65% ± 20% and 68% (interquartile range [IQR] 53%-79%). The median times below and above the therapeutic range were 17% (IQR 8%-29%) and 10% (IQR 3%-19%), respectively. Patients with renal dysfunction, advanced heart failure, frailty, prior valve surgery, and higher risk for bleeding (ATRIA score) or stroke (CHA2DS2-VASc score) had significantly lower TTR (P range. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Efficacy and safety of rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome: Rationale and design of the Trial on Rivaroxaban in AntiPhospholipid Syndrome (TRAPS) trial.

    Science.gov (United States)

    Pengo, V; Banzato, A; Bison, E; Zoppellaro, G; Padayattil Jose, S; Denas, G

    2016-03-01

    New oral anticoagulants may simplify long-term therapy in conditions requiring anticoagulation. Rivaroxaban is a direct factor Xa inhibitor that has been extensively studied and is now approved for the prevention and therapy of a number of thromboembolic conditions. This is a multicentre, randomized, open-label, study that will evaluate if Rivaroxaban 20 mg od (or 15 mg od in patients with moderate renal insufficiency) is non-inferior to warfarin (INR target 2.5), for the prevention of thromboembolic events, major bleeding and death in high risk (triple positive) patients with antiphospholipid syndrome. Secondary endpoints will assess the incidence of any individual component of the composite end point. An external adjudication committee will evaluate all suspected outcome events. This will be a unique trial, as it will enrol the biggest homogenous cohort of high risk APS individuals. The methods and the study design should be appropriate to achieve study results that are both scientifically valid and relevant to clinical practice. © The Author(s) 2015.

  1. Oral candidiasis.

    Science.gov (United States)

    Millsop, Jillian W; Fazel, Nasim

    2016-01-01

    Oral candidiasis (OC) is a common fungal disease encountered in dermatology, most commonly caused by an overgrowth of Candida albicans in the mouth. Although thrush is a well-recognized presentation of OC, it behooves clinicians to be aware of the many other presentations of this disease and how to accurately diagnose and manage these cases. The clinical presentations of OC can be broadly classified as white or erythematous candidiasis, with various subtypes in each category. The treatments include appropriate oral hygiene, topical agents, and systemic medications. This review focuses on the various clinical presentations of OC and treatment options. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Oral myiasis

    Directory of Open Access Journals (Sweden)

    Treville Pereira

    2010-01-01

    Full Text Available Myiasis is a relatively rare condition arising from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. It is an uncommon clinical condition, being more frequent in underdeveloped countries and hot climate regions, and is associated with poor hygiene, suppurative oral lesions; alcoholism and senility. Its diagnosis is made basically by the presence of larvae. The present article reports a case of oral myiasis involving 20 larvae in a patient with neurological deficiency.

  3. Hypertensive Crisis and Left Ventricular Thrombi after an Upper Respiratory Infection during the Long-term Use of Oral Contraceptives.

    Science.gov (United States)

    Suzuki, Natsuko; Suzuki, Keisuke; Mizuno, Tomofumi; Kato, Yukari; Suga, Norihiro; Yoshino, Masabumi; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

    2016-01-01

    A 34-year-old woman who had been using oral contraceptives for 10 years developed hypertensive crisis with papilloedema after an upper respiratory infection. Laboratory data showed hyperreninemic hyperaldosteronism and elevated levels of fibrinogen, fibrin, and fibrinogen degradation products. Echocardiography demonstrated two masses (18 mm) in the left ventricle. On the fourth hospital day, cerebral infarction, renal infarction, and upper mesenteric artery occlusion suddenly occurred despite the blood pressure being well-controlled using anti-hypertensive drugs. Echocardiography revealed the disappearance of the left ventricular masses, which suggested left ventricular thrombi. Cessation of the contraceptives and administration of heparin, warfarin, and anti-platelets drugs improved her general condition.

  4. LEFT ATRIAL APPENDAGE CLOSURE AS AN ALTERNATIVE TO WARFARIN FOR STROKE PREVENTION IN ATRIAL FIBRILLATION: A PATIENT¬LEVEL META¬ANALYSIS

    Directory of Open Access Journals (Sweden)

    2015-01-01

    Full Text Available Holmes D.R. Jr, Doshi S.K., Kar S., et al. Left Atrial Appendage Closure as an Alternative to Warfarin for Stroke Prevention in Atrial Fibrillation: A Patient­Level Meta­Analysis // J. Am. Coll. Cardiol. – 2015. – Vol. 65. – P. 2614–2623.

  5. Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes

    Czech Academy of Sciences Publication Activity Database

    Rulcová, A.; Prokopová, I.; Krausová, L.; Bitman, M.; Vrzal, R.; Dvořák, Z.; Blahoš, Jaroslav; Pávek, P.

    2010-01-01

    Roč. 8, č. 12 (2010), s. 2708-2717 ISSN 1538-7933 R&D Projects: GA MŠk(CZ) LC06063 Institutional research plan: CEZ:AV0Z50520514 Keywords : CYP3A4 * gene regulation * warfarin Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.439, year: 2010

  6. Efficacy and safety of rivaroxaban versus warfarin in patients from mainland China with nonvalvular atrial fibrillation: A subgroup analysis from the ROCKET AF trial.

    Science.gov (United States)

    Sun, Yihong; Hu, Dayi; Stevens, Susanna; Lokhnygina, Yuliya; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Hacke, Werner; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Piccini, Jonathan P; Singer, Daniel E; Fox, Keith A A; Patel, Manesh R

    2017-08-01

    The ROCKET AF study evaluated once-daily rivaroxaban versus dose-adjusted warfarin for the prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). In this analysis, we compared rivaroxaban with warfarin in patients with AF from China, East Asia, and the rest of the world (ROW). We assessed baseline demographics and interaction of treatment effects of rivaroxaban versus warfarin among patients from mainland China, other East Asian countries, and ROW. Of the 14,236 patients enrolled in the per-protocol population, 495 were from mainland China, 433 from other East-Asian regions, and 13,308 from the rest of the world (ROW). At baseline, patients from China had significantly higher rates of previous stroke/transient ischemic attack (TIA) compared with patients from other East Asian regions and ROW (79.6%, 44.6%, 51.6% respectively; p0.12). Numerically higher rates of intracranial bleeding were seen in patients from China receiving warfarin versus rivaroxaban. In patients from China, rates of intracranial hemorrhage were numerically lower among those receiving rivaroxaban and consistent with the overall trial. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Oral cancer

    Science.gov (United States)

    ... cancers tend to spread quickly. Smoking and other tobacco use are linked to most cases of oral cancer. Heavy alcohol use also increases the risk for ... cancer greatly increases the chance of survival. Prevention ... Avoiding smoking or other tobacco use Having dental problems corrected Limiting or avoiding alcohol ...

  8. Oral leukoplakia

    DEFF Research Database (Denmark)

    Holmstrup, Palle; Dabelsteen, Erik

    2016-01-01

    nature is oral leukoplakia, and for decades it has been discussed how to treat these lesions. Various treatment modalities, such as systemic therapies and surgical removal, have been suggested. The systemic therapies tested so far include retinoids, extracts of green tea, inhibitors of cyclooxygenase-2...

  9. Oral leukoplakia

    DEFF Research Database (Denmark)

    Kjærgaard Larsen, Marie; Sorensen, J. A.; Godballe, C.

    2016-01-01

    BACKGROUND AND AIM: Oral leukoplakia (OL) is a common premalignant lesion. The possible benefits of specific interventions in preventing a malignant transformation of OL are not well understood. This review assesses different invasive treatment techniques for OL and evaluate the optimal treatment...

  10. Oral calcitonin

    Directory of Open Access Journals (Sweden)

    Hamdy RC

    2012-09-01

    Full Text Available Ronald C Hamdy,1,2 Dane N Daley11Osteoporosis Center, College of Medicine, East Tennessee State University, 2Veterans Affairs Medical Center, Johnson City, TN, USAAbstract: Calcitonin is a hormone secreted by the C-cells of the thyroid gland in response to elevations of the plasma calcium level. It reduces bone resorption by inhibiting mature active osteoclasts and increases renal calcium excretion. It is used in the management of postmenopausal osteoporosis, Paget's disease of bone, and malignancy-associated hypercalcemia. Synthetic and recombinant calcitonin preparations are available; both have similar pharmacokinetic and pharmacodynamic profiles. As calcitonin is a peptide, the traditional method of administration has been parenteral or intranasal. This hinders its clinical use: adherence with therapy is notoriously low, and withdrawal from clinical trials has been problematic. An oral formulation would be more attractive, practical, and convenient to patients. In addition to its effect on active osteoclasts and renal tubules, calcitonin has an analgesic action, possibly mediated through β-endorphins and the central modulation of pain perception. It also exerts a protective action on cartilage and may be useful in the management of osteoarthritis and possibly rheumatoid arthritis. Oral formulations of calcitonin have been developed using different techniques. The most studied involves drug-delivery carriers such as Eligen® 8-(N-2hydroxy-5-chloro-benzoyl-amino-caprylic acid (5-CNAC (Emisphere Technologies, Cedar Knolls, NJ. Several factors affect the bioavailability and efficacy of orally administered calcitonin, including amount of water used to take the tablet, time of day the tablet is taken, and proximity to intake of a meal. Preliminary results looked promising. Unfortunately, in two Phase III studies, oral calcitonin (0.8 mg with 200 mg 5-CNAC, once a day for postmenopausal osteoporosis and twice a day for osteoarthritis failed to

  11. Safety and Efficacy of Bridging With Low-Molecular-Weight Heparin During Temporary Interruptions of Warfarin: A Register-Based Cohort Study.

    Science.gov (United States)

    Sjögren, Vilhelm; Grzymala-Lubanski, Bartosz; Renlund, Henrik; Svensson, Peter J; Själander, Anders

    2017-11-01

    Low-molecular-weight heparin (LMWH) is often recommended as a bridging therapy during temporary interruptions in warfarin treatment, despite lack of evidence. The aim of this study was to see whether we could find benefit from LMWH bridging. We studied all planned interruptions of warfarin within the Swedish anticoagulation register Auricula during 2006 to 2011. Low-molecular-weight heparin bridging was compared to nonbridging (control) after propensity score matching. Complications were identified in national clinical registers for 30 days following warfarin cessation, and defined as all-cause mortality, bleeding (intracranial, gastrointestinal, or other), or thrombosis (ischemic stroke or systemic embolism, venous thromboembolism, or myocardial infarction) that was fatal or required hospital care. Of the 14 556 identified warfarin interruptions, 12 659 with a known medical background had a mean age of 69 years, 61% were males, mean CHADS 2 (1 point for each of congestive heart failure, hypertension, age ≥75 years, diabetes, and 2 points for stroke or transient ischemic attack) score was 1.7, and CHA 2 DS 2 -VASc score was 3.4. The total number of LMWH bridgings was 7021. Major indications for anticoagulation were mechanical heart valve prostheses 4331, atrial fibrillation 1097, and venous thromboembolism 1331. Bridging patients had a higher rate of thrombotic events overall. Total risk of any complication did not differ significantly between bridging (1.5%) and nonbridging (1.2%). Regardless of indication for warfarin treatment, we found no benefit from bridging. The type of procedure prompting bridging was not known, and the likely reason for the observed higher risk of thrombosis with LMWH bridging is that low-risk procedures more often meant no bridging. Results from randomized trials are needed, especially for patients with mechanical heart valves.

  12. A prospective randomized trial of aspirin-clopidogrel combination therapy and dose-adjusted warfarin on indices of thrombogenesis and platelet activation in atrial fibrillation.

    Science.gov (United States)

    Kamath, Sridhar; Blann, Andrew D; Chin, Bernard S P; Lip, Gregory Y H

    2002-08-07

    This study was designed to investigate whether or not combination aspirin-clopidogrel therapy would reduce markers of thrombogenesis and platelet activation in atrial fibrillation (AF), in a manner similar to warfarin. Dose-adjusted warfarin is beneficial as thromboprophylaxis in AF, but potentially serious side effects and regular monitoring leave room for alternative therapies. METHODS; We randomized 70 patients with nonvalvular AF who were not on any antithrombotic therapy to either dose-adjusted warfarin (international normalized ratio 2 to 3) (Group I) or combination therapy with aspirin 75 mg and clopidogrel 75 mg (Group II). Plasma indices of thrombogenesis (fibrin D-dimer, prothrombin fragment 1+2) and platelet activation (beta-thromboglobulin [TG] and soluble P-selectin) were quantified, along with platelet aggregation responses to standard agonists, at baseline (pretreatment) and at six weeks posttreatment. RESULTS; Pretreatment levels of fibrin D-dimer (p = 0.001), beta-TG (p = 0.01) and soluble P-selectin (p = 0.03) were raised in patients with AF, whereas plasma prothrombin fragment 1+2 levels and platelet aggregation were not significantly different compared with controls. Dose-adjusted warfarin reduced plasma levels of fibrin D-dimer, prothrombin fragment 1+2 and beta-thromboglobulin levels at six weeks (all p failed to reduce plasma indices of thrombogenesis and platelet activation in AF, although some aspects of ex vivo platelet aggregation were altered. Anticoagulation with warfarin may be superior to combination aspirin-clopidogrel therapy as thromboprophylaxis in AF.

  13. Efficacy and safety of rivaroxaban compared with warfarin in patients with carotid artery disease and nonvalvular atrial fibrillation: Insights from the ROCKET AF trial.

    Science.gov (United States)

    Kochar, Ajar; Hellkamp, Anne S; Lokhnygina, Yuliya; Jones, W Schuyler; Becker, Richard C; Berkowitz, Scott D; Breithardt, Günter; Fox, Keith A A; Halperin, Jonathan L; Hankey, Graeme J; Mahaffey, Kenneth W; Nessel, Christopher C; Singer, Daniel E; Piccini, Jonathan P; Patel, Manesh R

    2018-01-01

    Atrial fibrillation (AF) increases risk of stroke 5-fold. Carotid artery disease (CD) also augments the risk of stroke, yet there are limited data about the interplay of these 2 diseases and clinical outcomes in patients with comorbid AF and CD. Among patients with both AF and CD, use of rivaroxaban when compared with warfarin is associated with a lower risk of stroke. This post hoc analysis from ROCKET AF aimed to determine absolute rates of stroke/systemic embolism (SE) and bleeding, and the efficacy and safety of rivaroxaban compared with warfarin in patients with AF and CD (defined as history of carotid occlusive disease or carotid revascularization [endarterectomy and/or stenting]). A total of 593 (4.2%) patients had CD at enrollment. Patients with and without CD had similar rates of stroke or SE (adjusted hazard ratio [HR]: 0.99, 95% confidence interval [CI]: 0.66-1.48, P = 0.96), and there was no difference in major or nonmajor clinically relevant bleeding (adjusted HR: 1.04, 95% CI: 0.88-1.24, P = 0.62). The efficacy of rivaroxaban compared with warfarin for the prevention of stroke/SE was not statistically significant in patients with vs those without CD (interaction P = 0.25). The safety of rivaroxaban vs warfarin for major or nonmajor clinically relevant bleeding was similar in patients with and without CD (interaction P = 0.64). Patients with CD in ROCKET AF had similar risk of stroke/SE compared with patients without CD. Additionally, there was no interaction between CD and the treatment effect of rivaroxaban or warfarin for stroke prevention or safety endpoints. © 2018 Wiley Periodicals, Inc.

  14. Comparison of the Non-VKA Oral Anticoagulants Apixaban, Dabigatran, and Rivaroxaban in the Extended Treatment and Prevention of Venous Thromboembolism: Systematic Review and Network Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    A T Cohen

    Full Text Available Historically, warfarin or aspirin have been the recommended therapeutic options for the extended treatment (>3 months of VTE. Data from Phase III randomised controlled trials (RCTs are now available for non-VKA oral anticoagulants (NOACs in this indication. The current systematic review and network meta-analysis (NMA were conducted to compare the efficacy and safety of anticoagulants for the extended treatment of VTE.Electronic databases (accessed July 2014 and updated April 2016 were systematically searched to identify RCTs evaluating apixaban, aspirin, dabigatran, edoxaban, rivaroxaban, and warfarin for the extended treatment of VTE. Eligible studies included adults with an objectively confirmed deep vein thrombosis, pulmonary embolism or both. A fixed-effect Bayesian NMA was conducted, and results were presented as relative risks (RRs. Sensitivity analyses examining (i the dataset employed according to the time frame for outcome assessment (ii the model used for the NMA were conducted.Eleven Phase III RCTs (examining apixaban, aspirin, dabigatran, rivaroxaban, warfarin and placebo were included. The risk of the composite efficacy outcome (VTE and VTE-related death was statistically significantly lower with the NOACs and warfarin INR 2.0-3.0 compared with aspirin, with no significant differences between the NOACs. Treatment with apixaban (RR 0.23, 95% CrI 0.10, 0.55 or dabigatran (RR 0.55, 95% Crl 0.43, 0.71 was associated with a statistically significantly reduced risk of 'major or clinically relevant non-major bleed' compared with warfarin INR 2.0-3.0. Apixaban also showed a significantly reduced risk compared with dabigatran (RR 0.42, 95% Crl 0.18, 0.97 and rivaroxaban (RR 0.23, 95% Crl 0.09, 0.59. Sensitivity analyses indicate that results were dependent on the dataset, but not on the type of NMA model employed.Results from the NMA indicate that NOACs are an effective treatment for prevention of VTE or VTE-related death in the extended

  15. Outpatient management of oral anticoagulation treatment (OAT in general practice: the “Medicina di Gruppo di Masate” experience

    Directory of Open Access Journals (Sweden)

    Fiorenzo Massimo Corti

    2017-04-01

    Full Text Available Outpatient management of oral anticoagulation treatment (OAT in general practice: the “Medicina di Gruppo di Masate” experienceOral anticoagulants are used for prophylaxis in thromboembolic conditions. Vitamin K antagonists (VKAs such as warfarin, are commonly employed. The anticoagulation activity induced by VKAs is monitored by the prothrombin time test to determine the International Normalized Ratio (INR. Point-of-care testing (POCT devices can be used to monitor anticoagulant therapy improving the quality of oral anticoagulation. This paper aims at describing the relevant experience of the “Medicina di Gruppo di Masate” in general practice. We also put this experience into the general context of the international evidence on the impact of POCT. Both our experience and the international evidence may support anticoagulant therapy management by GPs (General Practitioners.

  16. Oral Histoplasmosis

    OpenAIRE

    Folk, Gillian A.; Nelson, Brenda L.

    2017-01-01

    A 44-year-old female presented to her general dentist with the chief complaint of a painful mouth sore of 2 weeks duration. Clinical examination revealed an irregularly shaped ulcer of the buccal and lingual attached gingiva of the anterior mandible. A biopsy was performed and microscopic evaluation revealed histoplasmosis. Histoplasmosis, caused by Histoplasma capsulate, is the most common fungal infection in the United States. Oral lesions of histoplasmosis are generally associated with the...

  17. Impact of Computer-Aided Warfarin Dosing in a Saudi Arabian ...

    African Journals Online (AJOL)

    in comparison to the manual method. The constant increase of patient numbers and their pressure on thrombosis centers have led to the development of alternative models for delivery of oral anticoagulation therapy [9]. Primary care, General. Practitioner, Patient self testing and self management and the use of CDSS has.

  18. Warfarin therapy and incidence of cerebrovascular complications in left-sided native valve endocarditis

    DEFF Research Database (Denmark)

    Snygg-Martin, U; Rasmussen, Rasmus Vedby; Hassager, C

    2011-01-01

    Anticoagulant therapy has been anticipated to increase the risk of cerebrovascular complications (CVC) in native valve endocarditis (NVE). This study investigates the relationship between ongoing oral anticoagulant therapy and the incidence of symptomatic CVC in left-sided NVE. In a prospective...

  19. Comparison of the Performance of the Warfarin Pharmacogenetics Algorithms in Patients with Surgery of Heart Valve Replacement and Heart Valvuloplasty.

    Science.gov (United States)

    Xu, Hang; Su, Shi; Tang, Wuji; Wei, Meng; Wang, Tao; Wang, Dongjin; Ge, Weihong

    2015-09-01

    A large number of warfarin pharmacogenetics algorithms have been published. Our research was aimed to evaluate the performance of the selected pharmacogenetic algorithms in patients with surgery of heart valve replacement and heart valvuloplasty during the phase of initial and stable anticoagulation treatment. 10 pharmacogenetic algorithms were selected by searching PubMed. We compared the performance of the selected algorithms in a cohort of 193 patients during the phase of initial and stable anticoagulation therapy. Predicted dose was compared to therapeutic dose by using a predicted dose percentage that falls within 20% threshold of the actual dose (percentage within 20%) and mean absolute error (MAE). The average warfarin dose for patients was 3.05±1.23mg/day for initial treatment and 3.45±1.18mg/day for stable treatment. The percentages of the predicted dose within 20% of the therapeutic dose were 44.0±8.8% and 44.6±9.7% for the initial and stable phases, respectively. The MAEs of the selected algorithms were 0.85±0.18mg/day and 0.93±0.19mg/day, respectively. All algorithms had better performance in the ideal group than in the low dose and high dose groups. The only exception is the Wadelius et al. algorithm, which had better performance in the high dose group. The algorithms had similar performance except for the Wadelius et al. and Miao et al. algorithms, which had poor accuracy in our study cohort. The Gage et al. algorithm had better performance in both phases of initial and stable treatment. Algorithms had relatively higher accuracy in the >50years group of patients on the stable phase. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Bleeding Risk and Antithrombotic Strategy in Patients With Sinus Rhythm and Heart Failure With Reduced Ejection Fraction Treated With Warfarin or Aspirin.

    Science.gov (United States)

    Ye, Siqin; Cheng, Bin; Lip, Gregory Y H; Buchsbaum, Richard; Sacco, Ralph L; Levin, Bruce; Di Tullio, Marco R; Qian, Min; Mann, Douglas L; Pullicino, Patrick M; Freudenberger, Ronald S; Teerlink, John R; Mohr, J P; Graham, Susan; Labovitz, Arthur J; Estol, Conrado J; Lok, Dirk J; Ponikowski, Piotr; Anker, Stefan D; Thompson, John L P; Homma, Shunichi

    2015-09-15

    We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of ≥2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. A team-based approach to warfarin management in long term care: a feasibility study of the MEDeINR electronic decision support system.

    Science.gov (United States)

    Papaioannou, Alexandra; Kennedy, Courtney C; Campbell, Glenda; Stroud, Jacqueline B; Wang, Luqi; Dolovich, Lisa; Crowther, Mark A

    2010-06-10

    Previous studies in long-term care (LTC) have demonstrated that warfarin management is suboptimal with preventable adverse events often occurring as a result of poor International Normalized Ratio (INR) control. To assist LTC teams with the challenge of maintaining residents on warfarin in the therapeutic range (INR of 2.0 to 3.0), we developed an electronic decision support system that was based on a validated algorithm for warfarin dosing. We evaluated the MEDeINR system in a pre-post implementation design by examining the impact on INR control, testing frequency, and experiences of staff in using the system. For this feasibility study, we piloted the MEDeINR system in six LTC homes in Ontario, Canada. All128 residents (without a prosthetic valve) who were taking warfarin were included. Three-months of INR data prior to MEDeINR was collected via a retrospective chart audit, and three-months of INR data after implementation of MEDeINR was captured in the central computer database. The primary outcomes compared in a pre-post design were time in therapeutic range (TTR) and time in sub/supratherapeutic ranges based on all INR measures for every resident on warfarin. Secondary measures included the number of monthly INR tests/resident and survey/focus-group feedback from the LTC teams. LTC homes in our study had TTR's that were higher than past reports prior to the intervention. Overall, the TTR increased during the MEDeINR phase (65 to 69%), but was only significantly increased for one home (62% to 71%, p management and decisions, and was generally easy to use. Although LTC homes in our sample had TTR's that were relatively high prior to the intervention, the MEDeINR program represented a useful tool to promote optimal TTR, decrease INR venipunctures, streamline processes, and increase nurse and physician confidence around warfarin management. We have demonstrated that MEDeINR was a practical, usable clinical information system that can be incorporated into the LTC

  2. Heparin requirements for full anticoagulation are higher for patients on dabigatran than for those on warfarin – a model-based study

    Directory of Open Access Journals (Sweden)

    Edrich T

    2015-02-01

    Full Text Available Thomas Edrich,1,2 Gyorgy Frendl,2 Gregory Michaud,3 Ioannis Ch Paschalidis4 1Department of Anesthesiology, Perioperative Medicine and General Intensive Care Medicine, Salzburg General Hospital and Paracelsus Private Medical University, Salzburg, Austria, 2Department of Anesthesiology, Perioperative and Pain Medicine, 3Department of Medicine, Division of Cardiology, Brigham and Women's Hospital, Harvard Medical School, 4Department of Electrical and Computer Engineering, Division of Systems Engineering, Boston University, Boston, MA, USA Purpose: Dabigatran (D is increasingly used for chronic anticoagulation in place of warfarin (W. These patients may present for catheter-based procedures requiring full anticoagulation with heparin. This study compares the heparin sensitivity of patients previously on dabigatran, on warfarin, or on no chronic anticoagulant during ablation of atrial fibrillation. Patients and methods: In a retrospective study of patients treated with D, W, or neither drug (N undergoing atrial ablation, the timing of heparin doses and resulting activated clotting times were collected. First, the initial activated clotting time response to the first heparin bolus was compared. Then, a non-linear mixed effects modelling (NONMEM analysis was performed, fitting a pharmacokinetic and -dynamic model to the entire anticoagulation course of each patient. Resulting model coefficients were used to compare the different patient groups. Results: Data for 66 patients on dabigatran, 95 patients on warfarin, and 27 patients on no anticoagulation were retrieved. The last dose of dabigatran or warfarin had occurred 27 hours and 15 hours before the procedure. Groups D and N both responded significantly less (P<0.05 to the initial heparin bolus than Group W (approximately 50%. Likewise, the model coefficients resulting from the fit to each group reflected a significantly lower heparin sensitivity in groups D and N compared to W. Clearances of the

  3. Efficacy and safety of rivaroxaban compared with warfarin in patients with peripheral artery disease and non-valvular atrial fibrillation: insights from ROCKET AF.

    Science.gov (United States)

    Jones, William Schuyler; Hellkamp, Anne S; Halperin, Jonathan; Piccini, Jonathan P; Breithardt, Gunter; Singer, Daniel E; Fox, Keith A A; Hankey, Graeme J; Mahaffey, Kenneth W; Califf, Robert M; Patel, Manesh R

    2014-01-01

    Vascular disease is included in a risk scoring system to predict stroke in patients with non-valvular atrial fibrillation (AF). This post hoc analysis of ROCKET AF aimed to determine the absolute rates of stroke and bleeding, and the relative effectiveness and safety of rivaroxaban vs. warfarin in patients with and without peripheral artery disease (PAD). Peripheral artery disease was defined on the case-report form as the presences of intermittent claudication, amputation for arterial insufficiency, vascular reconstruction, bypass surgery, or percutaneous intervention to the extremities, or previously documented abdominal aortic aneurysm. ROCKET AF was a double-blind, double-dummy, randomized-controlled trial comparing rivaroxaban and warfarin for the prevention of stroke or systemic embolism. A total of 839 (5.9%) patients in ROCKET AF had PAD. Patients with and without PAD had similar rates of stroke or systemic embolism [HR: 1.04, 95% CI (0.72, 1.50), P = 0.84] and major or non-major clinically relevant (NMCR) bleeding [HR: 1.11, 95% CI (0.96, 1.28), P = 0.17], respectively. The efficacy of rivaroxaban when compared with warfarin for the prevention of stroke or systemic embolism was similar in patients with PAD (HR: 1.19, 95% CI: 0.63-2.22) and without PAD (HR: 0.86, 95% CI: 0.73-1.02; interaction P = 0.34). There was a significant interaction for major or NMCR bleeding in patients with PAD treated with rivaroxaban compared with warfarin (HR: 1.40, 95% CI: 1.06-1.86) compared with those without PAD (HR: 1.03, 95% CI: 0.95-1.11; interaction P = 0.037). Patients with PAD in ROCKET AF did not have a statistically significant higher risk of stroke or systemic embolism than patients without PAD, and there were similar efficacy outcomes in patients treated with rivaroxaban and warfarin. In PAD patients, there was a higher risk of major bleeding or NMCR bleeding with rivaroxaban when compared with warfarin (interaction P = 0.037). Further investigation is warranted to

  4. A net clinical benefit analysis of warfarin and aspirin on stroke in patients with atrial fibrillation: a nested case–control study

    Directory of Open Access Journals (Sweden)

    Azoulay Laurent

    2012-06-01

    Full Text Available Abstract Background As the management of patients treated with anticoagulants and antiplatelet drugs entails balancing coagulation levels, we evaluated the net clinical benefit of warfarin and aspirin on stroke in a large cohort of patients with atrial fibrillation (AF. Methods A population-based cohort study of all patients at least 18 years of age with a first-ever diagnosis of chronic AF during the period 1993–2008 was conducted within the United Kingdom General Practice Research Database. A nested case–control analysis was conducted to estimate the risk of ischemic stroke and intracranial hemorrhage associated with the use of warfarin and aspirin. Cases were matched up to 10 controls on age, sex, and date of cohort entry. The adjusted net clinical benefit of warfarin and aspirin (expressed as the number of strokes prevented per 100 persons per year was calculated by subtracting the ischemic stroke rate (prevented by therapy from the intracranial hemorrhage (ICH rate (increased by therapy. Results The cohort included 70,766 patients newly-diagnosed with chronic AF, of whom 5519 experienced an ischemic stroke and 689 an ICH during follow-up. The adjusted net clinical benefit of warfarin was 0.59 (95% CI: 0.45, 0.73. However, the benefit was not seen for patients below (0.08, 95%: -0.38, 0.54 and above (−0.49, 95% CI: -1.13, 0.15 therapeutic range. The net clinical benefit of warfarin, apparent after 3 months of continuous use, increased as a function of CHADS2 score. The net clinical benefit was not significant with aspirin (−0.07, 95% CI: -0.22, 0.08, though it was seen in certain subgroups. Conclusions Warfarin provides a net clinical benefit in patients with atrial fibrillation, which is maintained with longer duration of use, particularly when used within therapeutic range. A similar net effect is not as clear with aspirin.

  5. Cost-effectiveness of new oral anticoagulants in the treatment and secondary prevention of venous thromboembolism

    Directory of Open Access Journals (Sweden)

    A. V. Rudakova

    2015-01-01

    Full Text Available Aim. To assess the cost-effectiveness of apixaban in the treatment and secondary prevention of venous thromboembolism (VTE compared with low molecular weight heparin (LMWH/warfarin and other new oral anticoagulants (NOACs. Material and methods. Cost-effectiveness analysis was performed using a Markov model, developed on the basis of the results of AMPLIFY AMPLIFY-Ext trials, and network meta-analyzes on the use of antithrombotic drugs in acute VTE and long-term administration after VTE. Markov cycle duration was 3 months. The duration of therapy in the simulation was 6 and 12 months. The time horizon of the study was 5 years. Life expectancy and costs were discounted by 3.5% per year. The costs on drugs were estimated based on the registered marginal cost price. Besides, the analysis was performed to the weighted average auctions prices for NOACs. The costs of monitoring and treatment of complications were calculated on the basis of the collective agreement of compulsory health insurance system (St. Petersburg, 2015. Results. Apixaban provided significant cost savings compared with other modes of anticoagulant therapy for hospital treatment. Apixaban provided cost savings compared with other NOACs with a minimal increase in life expectancy with regard to quality in long-term analysis. Apixaban provided an increase in life expectancy compared with the appointment of LMWH/warfarin, but required some increase in costs. At therapy duration of 6 months, the costs per one additional year of life with regard to quality and to one additional calendar year of life were 309.8-403.7 and 481.6-627.4 thousand rubles, respectively; at therapy duration of 12 months – 1254.4-1476.9 and 649.0-764.1 thousand rubles, respectively. Conclusion. Apixaban provided a reduction in the incidence of bleeding compared with other NOACs and LMWH/warfarin with comparable efficacy in treatment and secondary prevention of VTE. Apixaban therapy costs were lower than these

  6. Oral Thrush (For Parents)

    Science.gov (United States)

    ... For Parents / Oral Thrush Print en español Muguet (candidiasis oral) What Is Oral Thrush? Oral thrush is a ... Candida overgrowth also causes diaper rash and vaginal yeast infections . Babies can have oral thrush and a diaper rash at the same ...

  7. Towards understanding oral health

    NARCIS (Netherlands)

    Zaura, E.; ten Cate, J.M.

    2015-01-01

    During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term ‘oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain

  8. Spontaneous sublingual and intramural small-bowel hematoma in a patient on oral anticoagulation

    Directory of Open Access Journals (Sweden)

    Mohamed Moftah

    2012-08-01

    Full Text Available Spontaneous sublingual hematoma and intramural small bowel hematoma are rare and serious complications of anticoagulant therapy. Though previously reported individually, there has been no previous report of the same two complications occurring in a single patient. A 71-year-old Caucasian man, who was on warfarin for atrial fibrillation, presented with difficulty in swallowing due to a sublingual hematoma. He was observed in our intensive care unit, his warfarin was held and he recovered with conservative management. He represented two months later with a two day history of abdominal pain and distension. An abdominopelvic computed tomography (CT scan now showed small bowel obstruction due to intramural small bowel hematoma and haemorrhagic ascites. Again, this was treated expectantly with a good outcome. In conclusion, life threatening haemorrhagic complications of oral anticoagulant therapy can recur. Conservative treatment is successful in most cases, but an accurate diagnosis is mandatory to avoid unnecessary surgery. CT scan is the investigation of choice for the diagnosis of suspected haemorrhagic complications of over coagulation.

  9. Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of the ARISTOTLE trial.

    Science.gov (United States)

    Easton, J Donald; Lopes, Renato D; Bahit, M Cecilia; Wojdyla, Daniel M; Granger, Christopher B; Wallentin, Lars; Alings, Marco; Goto, Shinya; Lewis, Basil S; Rosenqvist, Mårten; Hanna, Michael; Mohan, Puneet; Alexander, John H; Diener, Hans-Christoph

    2012-06-01

    In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18,201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with

  10. THE CONTROL OF INTERNATIONAL NORMALISED RATIO IN PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH WARFARIN IN OUTPATIENT AND HOSPITAL SETTINGS: DATA FROM RECVASA REGISTRIES

    Directory of Open Access Journals (Sweden)

    M. M. Loukianov

    2018-01-01

    Full Text Available Am. To study in the RECVASA registers the availability of data about the international normalized ratio (INR indicator and achievement of its target values in outpatient and hospital practice in patients with atrial fibrillation (AF receiving anticoagulant therapy with warfarin.Material and methods. Data about the INR control and the frequency of achievement of its target values at the outpatient and hospital stages were analyzed in RECVASA (Ryazan and RECVASA FP – Yaroslavl outpatient registries, as well as in the hospital registers RECVASA FP (Moscow, Kursk, Tula in 817 patients (46.9% of men, age 68.5±9.6 years with AF and the prescribed anticoagulant therapy with warfarin.Results. INR was determined in 689 (84.3% of 817 patients. The values of INR were monitored during therapy with warfarin in RECVASA (Ryazan and RECVASA FP –Yaroslavl outpatient registries in 73.7% and 77.7% of patients, respectively, and in RECVASA FP hospital registers: 95.8% (Moscow; 81.3% (Tula and 93.5% (Kursk. The target level of INR (2.0-3.0 was achieved in a minority of patients with AF during treatment with warfarin: inRyazan – in 26.3% of cases;Yaroslavl – 38.3%;Kursk – 34.8%;Moscow – 39.5%; Tule – 26.3%. Control of INR in hospital registries during warfarin therapy in patients with AF significantly more often (p<0.05 was performed at the hospital stage, compared with prehospital (in Kursk –2.3 times more often in Moscow – 2.6 times, in Tula – in 1,8 times. The target level of INR in the hospital was achieved significantly more often (p<0.05 than before hospitalization (Moscow andKursk, but no significant differences were found in the RECVASA FP –Tula register (p=0.08. The INR was monitored by 94.9% of the patients; however, the target values of this indicator were achieved only in 33% of cases in the sample study in the RECVASA FP –Moscow registry according to a survey of 39 patients with AF who continued to receive warfarin after 2.6±0

  11. Specific antidotes against direct oral anticoagulants: A comprehensive review of clinical trials data.

    Science.gov (United States)

    Tummala, Ramyashree; Kavtaradze, Ana; Gupta, Anjan; Ghosh, Raktim Kumar

    2016-07-01

    The Vitamin K antagonist warfarin was the only oral anticoagulant available for decades for the treatment of thrombosis and prevention of thromboembolism until Direct Oral Anticoagulants (DOACs); a group of new oral anticoagulants got approved in the last few years. Direct thrombin inhibitor: dabigatran and factor Xa inhibitors: apixaban, rivaroxaban, and edoxaban directly inhibit the coagulation cascade. DOACs have many advantages over warfarin. However, the biggest drawback of DOACs has been the lack of specific antidotes to reverse the anticoagulant effect in emergency situations. Activated charcoal, hemodialysis, and activated Prothrombin Complex Concentrate (PCC) were amongst the nonspecific agents used in a DOAC associated bleeding but with limited success. Idarucizumab, the first novel antidote against direct thrombin inhibitor dabigatran was approved by US FDA in October 2015. It comprehensively reversed dabigatran-induced anticoagulation in a phase I study. A phase III trial on Idarucizumab also complete reversal of anticoagulant effect of dabigatran. Andexanet alfa (PRT064445), a specific reversal agent against factor Xa inhibitors, showed a complete reversal of anticoagulant activity of apixaban and rivaroxaban within minutes after administration without adverse effects in two recently completed parallel phase III trials ANNEXA-A and ANNEXA-R respectively. It is currently being studied in ANNEXA-4, a phase IV study. Aripazine (PER-977), the third reversal agent, has shown promising activity against dabigatran, apixaban, rivaroxaban, as well as subcutaneous fondaparinux and LMWH. This review article summarizes pharmacological characteristics of these novel antidotes, coagulation's tests affected, available clinical and preclinical data, and the need for phase III and IV studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Assessment and evaluation efficacy of a clinical pharmacist-led inpatient warfarin knowledge education program and follow-up at a Chinese tertiary referral teaching hospital

    Directory of Open Access Journals (Sweden)

    Guy-Armel Bounda

    2013-01-01

    Conclusion: Chinese patients on warfarin therapy should benefit from periodic educational efforts reinforcing key medication safety information. Patient education is not a once-off procedure. A complete patient education program run by a clinical pharmacist in a Cardio-thoracic ward can considerably improve and enhance to reduce the hospital stays and significantly enlighten the role of the patient education in adherence to therapy.

  13. Impact of Global Geographic Region on Time in Therapeutic Range on Warfarin Anticoagulant Therapy: Data From the ROCKET AF Clinical Trial

    Science.gov (United States)

    Singer, Daniel E.; Hellkamp, Anne S.; Piccini, Jonathan P.; Mahaffey, Kenneth W.; Lokhnygina, Yuliya; Pan, Guohua; Halperin, Jonathan L.; Becker, Richard C.; Breithardt, Günter; Hankey, Graeme J.; Hacke, Werner; Nessel, Christopher C.; Patel, Manesh R.; Califf, Robert M.; Fox, Keith A. A.

    2013-01-01

    Background Vitamin K antagonist (VKA) therapy remains the most common method of stroke prevention in patients with atrial fibrillation. Time in therapeutic range (TTR) is a widely cited measure of the quality of VKA therapy. We sought to identify factors associated with TTR in a large, international clinical trial. Methods and Results TTR (international normalized ratio [INR] 2.0 to 3.0) was determined using standard linear interpolation in patients randomized to warfarin in the ROCKET AF trial. Factors associated with TTR at the individual patient level (i‐TTR) were determined via multivariable linear regression. Among 6983 patients taking warfarin, recruited from 45 countries grouped into 7 regions, the mean i‐TTR was 55.2% (SD 21.3%) and the median i‐TTR was 57.9% (interquartile range 43.0% to 70.6%). The mean time with INR 3 was 15.7%. While multiple clinical features were associated with i‐TTR, dominant determinants were previous warfarin use (mean i‐TTR of 61.1% for warfarin‐experienced versus 47.4% in VKA‐naïve patients) and geographic region where patients were managed (mean i‐TTR varied from 64.1% to 35.9%). These effects persisted in multivariable analysis. Regions with the lowest i‐TTRs had INR distributions shifted toward lower INR values and had longer inter‐INR test intervals. Conclusions Independent of patient clinical features, the regional location of medical care is a dominant determinant of variation in i‐TTR in global studies of warfarin. Regional differences in mean i‐TTR are heavily influenced by subtherapeutic INR values and are associated with reduced frequency of INR testing. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:23525418

  14. Predictors of perioperative major bleeding in patients who interrupt warfarin for an elective surgery or procedure: Analysis of the BRIDGE trial.

    Science.gov (United States)

    Clark, Nathan P; Douketis, James D; Hasselblad, Vic; Schulman, Sam; Kindzelski, Andrei L; Ortel, Thomas L

    2018-01-01

    The use of low-molecular weight heparin bridge therapy during warfarin interruption for elective surgery/procedures increases bleeding. Other predictors of bleeding in this setting are not well described. BRIDGE was a randomized, double-blind, placebo-controlled trial of bridge therapy with dalteparin 100 IU/kg twice daily in patients with atrial fibrillation requiring warfarin interruption. Bleeding outcomes were documented from the time of warfarin interruption until up to 37 days postprocedure. Multiple logistic regression and time-dependent hazard models were used to identify major bleeding predictors. We analyzed 1,813 patients of whom 895 received bridging and 918 received placebo. Median patient age was 72.6 years, and 73.3% were male. Forty-one major bleeding events occurred at a median time of 7.0 days (interquartile range, 4.0-18.0 days) postprocedure. Bridge therapy was a baseline predictor of major bleeding (odds ratio [OR]=2.4, 95% CI: 1.2-4.8), as were a history of renal disease (OR=2.9, 95% CI: 1.4-6.0), and high-bleeding risk procedures (vs low-bleeding risk procedures) (OR=2.9, 95% CI: 1.4-5.9). Perioperative aspirin use (OR=3.6, 95% CI: 1.1-11.9) and postprocedure international normalized ratio >3.0 (OR=2.1, 95% CI: 1.5-3.1) were time-dependent predictors of major bleeding. Major bleeding was most common in the first 10 days compared with 11-37 days postprocedure (OR=3.5, 95% CI: 1.8-6.9). In addition to bridge therapy, perioperative aspirin use, postprocedure international normalized ratio >3.0, a history of renal failure, and having a high-bleeding risk procedure increase the risk of major bleeding around the time of an elective surgery/procedure requiring warfarin interruption. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Oral Anticoagulants to Prevent Stroke in Nonvalvular Atrial Fibrillation in Patients With CKD Stage 5D: An NKF-KDOQI Controversies Report.

    Science.gov (United States)

    Bansal, Vinod K; Herzog, Charles A; Sarnak, Mark J; Choi, Michael J; Mehta, Ravindra; Jaar, Bernard G; Rocco, Michael V; Kramer, Holly

    2017-12-01

    Stroke risk may be more than 3-fold higher among patients with chronic kidney disease stage 5D (CKD-5D) compared to the general population, with the highest stroke rates noted among those 85 years and older. Atrial fibrillation (AF), a strong risk factor for stroke, is the most common arrhythmia and affects >7% of the population with CKD-5D. Warfarin use is widely acknowledged as an important intervention for stroke prevention with nonvalvular AF in the general population. However, use of oral anticoagulants for stroke prevention in patients with CKD-5D and nonvalvular AF continues to be debated by the nephrology community. In this National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) controversies report, we discuss the existing observational studies that examine warfarin use and associated stroke and bleeding risks in adults with CKD-5D and AF. Non-vitamin K-dependent oral anticoagulants and their potential use for stroke prevention in patients with CKD-5D and nonvalvular AF are also discussed. Data from randomized clinical trials are urgently needed to determine the benefits and risks of oral anticoagulant use for stroke prevention in the setting of AF among patients with CKD-5D. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  16. Oral sex, oral health and orogenital infections

    Directory of Open Access Journals (Sweden)

    Saini Rajiv

    2010-01-01

    Full Text Available Oral sex is commonly practiced by sexually active male-female and same-gender couples of various ages, including adolescents. The various type of oral sex practices are fellatio, cunnilingus and analingus. Oral sex is infrequently examined in research on adolescents; oral sex can transmit oral, respiratory, and genital pathogens. Oral health has a direct impact on the transmission of infection; a cut in your mouth, bleeding gums, lip sores or broken skin increases chances of infection. Although oral sex is considered a low risk activity, it is important to use protection and safer sex precautions. There are various methods of preventing infection during oral sex such as physical barriers, health and medical issues, ethical issues and oral hygiene and dental issues. The lesions or unhealthy periodontal status of oral cavity accelerates the phenomenon of transmission of infections into the circulation. Thus consequences of unhealthy or painful oral cavity are significant and oral health should be given paramount importance for the practice of oral sex.

  17. VKORC1, CYP2C9 and CYP4F2 genetic-based algorithm for warfarin dosing: an Italian retrospective study.

    Science.gov (United States)

    Zambon, Carlo-Federico; Pengo, Vittorio; Padrini, Roberto; Basso, Daniela; Schiavon, Stefania; Fogar, Paola; Nisi, Alessandra; Frigo, Anna Chiara; Moz, Stefania; Pelloso, Michela; Plebani, Mario

    2011-01-01

    A total of 371 patients under stable warfarin therapy were retrospectively selected to develop a pharmacogenetic algorithm to identify the individual maintenance dose. The variables that were entered into the algorithm were: VKORC1, CYP2C9 and CYP4F2 polymorphisms, body surface area and age. The percentage of cases whose predicted mean weekly warfarin dose was within 20% of the actual maintenance dose was 51.8% considering patients overall, and were 36.2, 66.2 and 55.4%, respectively, taking into account patients requiring low (≤25 mg/week), intermediate (25-45 mg/week) and high (≥45 mg/week) doses. The algorithm could correctly assign 73.8 and 63.2% of patients to the low- and high-dose regimens, respectively. We developed and validated a pharmacogenetic algorithm in a series of Italian patients, we then tested, in the same series of italian patients, the formulas of three published algorithms. These three algorithms were developed and validated by their authors in a series of patients different from our own. The performance of our algorithm in our patients series was slightly higher than that achieved when using the three other algorithms in our patients series. The high predictive accuracy of low and high warfarin requirements of our algorithm warrants its application in prospective studies for clinical validation.

  18. Efficacy and safety of apixaban compared with warfarin according to age for stroke prevention in atrial fibrillation: observations from the ARISTOTLE trial.

    Science.gov (United States)

    Halvorsen, Sigrun; Atar, Dan; Yang, Hongqiu; De Caterina, Raffaele; Erol, Cetin; Garcia, David; Granger, Christopher B; Hanna, Michael; Held, Claes; Husted, Steen; Hylek, Elaine M; Jansky, Petr; Lopes, Renato D; Ruzyllo, Witold; Thomas, Laine; Wallentin, Lars

    2014-07-21

    The risk of stroke in patients with atrial fibrillation (AF) increases with age. In the ARISTOTLE trial, apixaban when compared with warfarin reduced the rate of stroke, death, and bleeding. We evaluated these outcomes in relation to patient age. A total of 18 201 patients with AF and a raised risk of stroke were randomized to warfarin or apixaban 5 mg b.d. with dose reduction to 2.5 mg b.d. or placebo in 831 patients with ≥2 of the following criteria: age ≥80 years, body weight ≤60 kg, or creatinine ≥133 μmol/L. We used Cox models to compare outcomes in relation to patient age during 1.8 years median follow-up. Of the trial population, 30% were 0.11 for all). Results were also consistent for the 13% of patients ≥80 years. No significant interaction with apixaban dose was found with respect to treatment effect on major outcomes. The benefits of apixaban vs. warfarin were consistent in patients with AF regardless of age. Owing to the higher risk at older age, the absolute benefits of apixaban were greater in the elderly. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology.

  19. Bilateral rectus sheath haematoma complicating dengue virus infection in a patient on warfarin for mechanical aortic valve replacement: a case report.

    Science.gov (United States)

    Rosa, Chamith Thushanga; Navinan, Mitrakrishnan Rayno; Samarawickrama, Sincy; Hamza, Himam; Gunarathne, Maheshika; Arulanantham, Arulprashanth; Subba, Neeha; Samarasiri, Udari; Mathias, Thushara; Kulatunga, Aruna

    2017-01-07

    The management of Dengue virus infection can be challenging. Varied presentations and numerous complications intrinsic to dengue by itself increase the complexity of treatment and potential mortality. When burdened with the presence of additional comorbidities and the need to continue compulsory medications, clear stepwise definitive guidance is lacking and patients tend to have more complex complications and outcomes calling to question the clinical decisions that may have been taken. The use and continuation of warfarin in dengue virus infection is one such example. We report a 65 year old South Asian female who presented with dengue fever. She had a history bronchial asthma, a prior abdominal surgery, and was on warfarin and maintained a therapeutically appropriate internationalized normalized ratio for a mechanical aortic valve replacement. Though preemptive decision to stop warfarin was taken with decreasing platelet counts, her clinical course was complicated with the development of bilateral rectus sheath haematoma's requiring resuscitation with blood transfusions. Though management of dengue viral fever has seen drastic evolution with recent updated guidance, clinical scenarios seen in the course of the illness still pose challenges to the managing physician. The need to continue obligatory anticoagulation which may seem counterintuitive during a complex disease such as dengue virus infection must be considered after understanding the potential risks versus that of its benefits. Though case by case decisions maybe warranted, a clear protocol would be very helpful in making clinical decisions, as the correct preemptive decision may potentially avert catastrophic and unpredictable bleeding events.

  20. Oral Health Glossary

    Science.gov (United States)

    ... 2018 About | Contact InfoBites Quick Reference Learn more Oral Health and Overal Health Gum Disease and Cardiovascular Health ... news feeds delivered directly to your desktop! more... Oral Health Glossary Article Chapters Oral Health Glossary print full ...

  1. Oral Cancer Exam

    Medline Plus

    Full Text Available ... Us Home Health Info Health Information The Oral Cancer Exam See a step-by-step video explaining what happens during an oral cancer examination. An oral cancer exam is painless and ...

  2. Oral Cancer Exam

    Medline Plus

    Full Text Available ... Contact Us Home Health Info Health Information The Oral Cancer Exam See a step-by-step video explaining what happens during an oral cancer examination. An oral cancer exam is painless and ...

  3. [Oral anticoagulants and medicinal plants. An emerging interaction].

    Science.gov (United States)

    Argento, A; Tiraferri, E; Marzaloni, M

    2000-01-01

    The consumption of herbal medicines is increasing steadily throughout the world, although to our knowledge there are neither studies on their effectiveness nor controls over the quality and safety of these preparations. Considered "food integrators", these preparations are marketed without restriction. It is a common notion that natural therapy has neither side nor toxic effects: allergic reactions, direct toxic effects or those due to contamination, carcinogenicity, mutagenicity, and heavy metal toxicity have been reported as adverse events caused by herbs. Rather than replacing traditional therapy, most herbal medical treatment is used in conjunction with it. Also, the attending physician is generally not informed that the patient is using herbs. Because Passionflower, hydroalcoholic extracts, Juniper and Verbena officinalis supply variable quantities of vitamin K, they can lessen the effect of oral anticoagulant therapy. Ganoderma Japonicum, Papaw, Salvia miltiorrhiza, Ginseng, Devil's claw, Garlic, Quinine, Ginkgo, Ginger, Red Clover and Horse-Chestnut reinforce warfarin action by heterogeneous mechanisms. They should thus not be used in patients on oral anticoagulant and/or antiplatelet therapy. The scientific community must take into account the adverse events caused by interaction between herbal medicine and conventional therapy, and patients must be informed of the dangers of these preparations. If a bleeding event occurs or the quality of anticoagulant therapy is poor, the clinician should consider the possibility of interaction between conventional therapy and herbal medicine that the patient has neglected to mention he is taking.

  4. Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Li

    Full Text Available Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbers of patients prescribed 2.5 mg twice-daily (BID apixaban. Using pooled data from 4 American claims database sources, baseline characteristics and outcomes for patients prescribed 5 mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1 propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and 6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients prescribed 2.5 mg BID apixaban were older, had clinically more severe comorbidities, and were more likely to have a history of stroke and bleeding compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.60-0.81 and major bleeding (HR: 0.59, 95% CI: 0.53-0.66. Compared with warfarin, 2.5 mg BID apixaban was also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49-0.81 and major bleeding (HR: 0.59, 95% CI: 0.49-0.71. In this real-world study, both apixaban doses were assessed in 2 patient groups differing in age and clinical characteristics. Each apixaban dose was associated with a lower risk of stroke/SE and major bleeding compared with warfarin in the distinct population for which it is being prescribed in United States clinical practice.Clinicaltrials.Gov Identifier: NCT03087487.

  5. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial.

    Science.gov (United States)

    Hu, Peter T; Lopes, Renato D; Stevens, Susanna R; Wallentin, Lars; Thomas, Laine; Alexander, John H; Hanna, Michael; Lewis, Basil S; Verheugt, Freek W A; Granger, Christopher B; Jones, W Schuyler

    2017-01-17

    We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD. The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had PAD at baseline. Patients with PAD had higher unadjusted rates of stroke and systemic embolism (hazard ratio [HR] 1.73, 95% CI 1.22-2.45; P=0.002) and major bleeding (HR 1.34, 95% CI 1.00-1.81; P=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (HR 1.32, 95% CI 0.93-1.88; P=0.12) and major bleeding (HR 1.03, 95% CI 0.76-1.40; P=0.83) compared with patients without PAD. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with PAD (HR 0.63, 95% CI 0.32-1.25) and without PAD (HR 0.80, 95% CI 0.66-0.96; interaction P=0.52). Patients with PAD did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (HR 1.05, 95% CI 0.69-1.58), whereas those without PAD had a statistically significant reduction (HR 0.65, 95% CI 0.58-0.73; interaction P=0.03). Patients with PAD in ARISTOTLE had a higher crude risk of stroke or systemic embolism compared with patients without PAD that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without PAD. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and PAD. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  6. Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

    Science.gov (United States)

    Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2015-01-01

    Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

  7. Barriers and facilitators to reducing frequent laboratory testing for patients who are stable on warfarin: a mixed methods study of de-implementation in five anticoagulation clinics.

    Science.gov (United States)

    Barnes, Geoffrey D; Misirliyan, Sevan; Kaatz, Scott; Jackson, Elizabeth A; Haymart, Brian; Kline-Rogers, Eva; Kozlowski, Jay; Krol, Gregory; Froehlich, James B; Sales, Anne

    2017-07-14

    Patients on chronic warfarin therapy require regular laboratory monitoring to safely manage warfarin. Recent studies have challenged the need for routine monthly blood draws in the most stable warfarin-treated patients, suggesting the safety of less frequent laboratory testing (up to every 12 weeks). De-implementation efforts aim to reduce the use of low-value clinical practices. To explore barriers and facilitators of a de-implementation effort to reduce the use of frequent laboratory tests for patients with stable warfarin management in nurse/pharmacist-run anticoagulation clinics, we performed a mixed-methods study conducted within a state-wide collaborative quality improvement collaborative. Using a mixed-methods approach, we conducted post-implementation semi-structured interviews with a total of eight anticoagulation nurse or pharmacist staff members at five participating clinic sites to assess barriers and facilitators to de-implementing frequent international normalized ratio (INR) laboratory testing among patients with stable warfarin control. Interview guides were based on the Tailored Implementation for Chronic Disease (TICD) framework. Informed by interview themes, a survey was developed and administered to all anticoagulation clinical staff (n = 62) about their self-reported utilization of less frequent INR testing and specific barriers to de-implementing the standard (more frequent) INR testing practice. From the interviews, four themes emerged congruent with TICD domains: (1) staff overestimating their actual use of less frequent INR testing (individual health professional factors), (2) barriers to appropriate patient engagement (incentives and resources), (3) broad support for an electronic medical record flag to identify potentially eligible patients (incentives and resources), and (4) the importance of personalized nurse/pharmacist feedback (individual health professional factors). In the survey (65% response rate), staff report offering less

  8. Mucosite oral

    Directory of Open Access Journals (Sweden)

    Sérgio Spezzia

    2016-04-01

    Full Text Available A mucosite consta de irritação ou inflamação da mucosa bucal, provocada por ação da radioterapia de cabeça e pescoço e da quimioterapia. O objetivo deste artigo foi verificar como a ocorrência de mucosite oral pode influir na saúde bucal dos pacientes com câncer. Para tratamento odontológico o laser de baixa intensidade é o de opção. O emprego do laser de baixa potência tem cunho, tanto preventivo, como curativo para tratamento das lesões causadas. Concluiu-se que se pode evitar intercorrências no transcorrer do tratamento oncológico radioterápico e quimioterápico, fazendo-se uso da terapia laser, o que vai permitir melhores condições e qualidade de vida aos pacientes acometidos por mucosite.

  9. Risk of bleeding and stroke with oral anticoagulation and antiplatelet therapy in patients with atrial fibrillation in Taiwan: a nationwide cohort study.

    Directory of Open Access Journals (Sweden)

    Pei-Chun Chen

    Full Text Available Data on the use of oral anticoagulation (OAC and antiplatelet therapy and the risk of bleeding and stroke amongst Asian patients with atrial fibrillation (AF are limited. We investigated the risks of bleeding and stroke with use of oral anticoagulation (OAC and antiplatelet therapy as mono- or combination therapy, in patients with AF from a Chinese nationwide cohort study.We studied a cohort of 10384 patients (57.2% men, age 67.8 ± 13.2 yrs between 1999 and 2010 from the National Health Insurance Research Database in Taiwan. Records of prescriptions were obtained during follow-up. The main outcome was a recurrent stroke during the follow-up period. Time-dependent Cox proportional hazards models were used for this analysis.We documented 1009 events for bleeding, as well as 224 hemorrhagic stroke and 1642 ischemic stroke events during a median 3.2 (interquartile range, 1.05-6.54 years' follow-up. Compared with warfarin users, patients with antiplatelet therapy had a lower risk of bleeding (adjusted relative risk [RR], 0.59, 95% confidence interval [CI], 0.49-0.71, p<0.001 whilst combination therapy had a non-statistically significant higher bleeding risk (RR, 1.33, 95%, 0.91-1.94, p = 0.20. Patients on antiplatelet monotherapy had a similar risk for ischemic stroke compared with OAC (RR 1.05, 95% CI, 0.89-1.25, p = 0.50, whilst those on combination therapy had a significantly higher risk (RR 1.90, 95% CI, 1.34-2.70, p<0.001.In a national representative cohort, antiplatelet therapy had no significant difference in ischemic stroke risk to warfarin. For bleeding, aspirin had a lower risk compared to warfarin. This may reflect poor anticoagulation control, highlighting important missed opportunities for improved stroke prevention, especially in countries where anticoagulation management is suboptimal.

  10. Effect of Complexation with Arabinogalactan on Pharmacokinetics of “Guest” Drugs in Rats: For Example, Warfarin

    Directory of Open Access Journals (Sweden)

    Mikhail V. Khvostov

    2013-01-01

    Full Text Available A pharmacokinetic study of the warfarin (WF : arabinogalactan (AG complex with the 1 : 10 mass ratio after its intragastric introduction to Wistar rats at a dose of 5 mg/kg (WF dose in the complex was 0.5 mg/kg once a day for three days was conducted. It was found that Cmax, T1/2, and AUC of WF in the complex form were lower than after the introduction of blank WF at the same dose, but its elimination (Cl, MRT was much faster. Significant accumulation (Cmin and an abrupt increase in plasma concentration after the third introduction were observed for blank WF, whereas the complex showed a much more moderate increase in concentration at this point. However, despite obvious differences in pharmacokinetic parameters, the efficacies of both agents were virtually identical; the complex differed from blank WF by only 15%. This value is rather insignificant and does not impair its anticoagulant activity. Thus, we can conclude that introduction of the WF : AG complex is safe in terms of reduction of the bleeding risk and accumulation.

  11. Safety of a clinical surveillance protocol with 3- and 6-week warfarin prophylaxis after total joint arthroplasty.

    Science.gov (United States)

    Goldstein, W M; Jimenez, M L; Bailie, D S; Wall, R; Branson, J

    2001-07-01

    The charts of 1869 patients were reviewed for the occurrence of deep venous thrombosis (DVT) and pulmonary embolism after total hip or knee arthroplasty. Prophylaxis consisted of 3 (group 1; n=1235) or 6 (group 2; n=634) weeks low-dose warfarin, pneumatic compression boots worn by patients in the hospital, mobilization on the first postoperative day, and a clinical surveillance protocol. Venous ultrasound or ventilation/perfusion lung scintigraphy (V/Q) was performed only if patients became symptomatic. patients. Twenty-three (1.8%) patients were positive for DVT. Ventilation/perfusion lung scintigraphy was performed on 25 patients, and 5 (0.4%) patients were positive for pulmonary embolism. In group 2, 117 patients were evaluated for DVT, and 19 (3%) patients had positive results determined by ultrasound. Twenty-five patients were evaluated with V/Q and only 1 (0.16%) patient was positive for pulmonary embolism. No patient developed a fatal pulmonary embolism or postphlebitic syndrome. This prophylaxis protocol is an efficient and cost-effective method for the prevention of significant events after surgery.

  12. THE PROBLEM OF THE USE OF NEW ORAL ANTICOAGULANTS IN CANCER PATIENTS RECEIVING CHEMOTHERAPY

    Directory of Open Access Journals (Sweden)

    A. A. Rumyantsev

    2014-01-01

    Full Text Available Despite large number of known risk factors of venous thromboembolism (VTE in cancer patients existing prediction models do not allow definite identification of cancer patients that have indications for anticoagulant prevention. Besides, heparin and warfarin use for VTE prevention in cancer is accompanied by some problems. New oral anticoagulants (NOAC are promising drugs for use in oncology practice; however their use is complicated by the lack of data on efficacy and safety in these patients, potential drug interactions and the possibility of unpredictable changes in effect during chemotherapy. Widespread use of NOAC for the prevention and treatment of tumor-associated VTE prior to phase III trials is not recommended. However, the criteria for selection of patients for whom the study of the efficacy and safety of NOAC is a priority can now be developed.

  13. Current guidelines and prospects for using novel oral anticoagulants for nonvalvular atrial fibrillation

    Directory of Open Access Journals (Sweden)

    A. V. Fonyakin

    2014-01-01

    Full Text Available The capabilities of antithrombotic therapy to prevent systemic thromboembolic events in nonvalvular atrial fibrillation (AF are substantially extended after clinically introducing novel oral anticoagulants (NOACs, such as dabigatran, rivaroxaban, and apixaban. World clinical experience with NOACs in AF has confirmed their efficacy and safety in both primary and secondary stroke prevention. At the same time, apixaban additionally reduces the risk of fatal outcomes and it is the safest among the NOACs against hemorrhagic events. The low risks of intracranial hemorrhage typical of NOACs should be taken into account when choosing oral anticoagulant therapy after hemorrhagic stroke in patients athigh risk for thromboembolic events due to AF. Whether NOACs may be used in acute myocardial infarction and during coronary stenting in the presence of nonvalvular AF, left ventricular thromboses, and cardiomyopathies is considered. In real clinical practice, nonvalvular AF may be accompanied by different cardiovascular diseases, by creating the situations where there are no specific guidelines for the use of NOACs. The results of comparing the clinical efficiency of different antithrombotic therapy regimens, the subanalysis of randomized trials, and experts’ opinions may assist a physician to substantiate their decisions. Thus, just a few NOACs that are similar and/or superior to warfarin in efficacy and safety have emerged to date. There are grounds to believe that many physicians will prefer direct anticoagulants to warfarin not only because of their proven efficacy, but also the rapid onset of their anticoagulant effect, neither interaction with a number of foods or drugs, and above all, nor need for regular laboratory blood testing. World post-marketingsurveillance and new clinical tests will be helpful in better estimating the benefits and risks of treatment with NOACs and in expanding indications for their use, which will considerably

  14. Low-molecular-weight heparinoid compared with warfarin for prophylaxis of deep-vein thrombosis in patients who are operated on for fracture of the hip. A prospective, randomized trial

    Energy Technology Data Exchange (ETDEWEB)

    Gerhart, T.N.; Yett, H.S.; Robertson, L.K.; Lee, M.A.; Smith, M.; Salzman, E.W. (Beth Israel Hospital, Boston, MA (USA))

    1991-04-01

    In a randomized, prospective trial, a low-molecular-weight heparinoid (Org 10172 (Lomoparan)) was compared with warfarin for efficacy and safety in preventing deep-vein thrombosis in 263 patients who had an operatively treated fracture of the hip. One group of patients received Org 10172 in a dose of 750 units subcutaneously every twelve hours until the ninth postoperative day; on the seventh postoperative day, warfarin was added to the regimen. The other group received only warfarin. Both drugs were begun preoperatively, immediately after the admission evaluation. In the patients who received warfarin, the desired prothrombin time was one and one-half times the control level. Deep-vein thrombosis was detected by {sup 125}I-fibrinogen scanning and impedance plethysmography and was confirmed by phlebography and compression ultrasonography. Deep-vein thrombosis was found in nine (7 per cent) of the 132 patients who received Org 10172 and in twenty-eight (21 per cent) of the 131 patients who received warfarin (p less than 0.001). Adverse reactions were not significantly different in the two groups. Major bleeding complications occurred in eight patients in the Org-10172 group, only four of whom were receiving the drug at the time of bleeding, and in five patients who were receiving warfarin (not significant). There was no difference in intraoperative loss of blood or in requirements for transfusion. We concluded that the low-molecular-weight heparinoid Org 10172 is a safe, convenient, effective antithrombotic agent for the prevention of venous thrombosis after an operation for fracture of the hip.

  15. Net clinical benefit of rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation: a subgroup analysis of J-ROCKET AF.

    Science.gov (United States)

    Uchiyama, Shinichiro; Hori, Masatsugu; Matsumoto, Masayasu; Tanahashi, Norio; Momomura, Shin-Ichi; Goto, Shinya; Izumi, Tohru; Koretsune, Yukihiro; Kajikawa, Mariko; Kato, Masaharu; Ueda, Hitoshi; Iekushi, Kazuma; Yamanaka, Satoshi; Tajiri, Masahiro

    2014-01-01

    The risk factors that have been identified for bleeding events with rivaroxaban are predominantly the same as those predicting thromboembolic ones in patients with atrial fibrillation (AF). Our aim was to determine the net clinical benefit (NCB) from the results of the J-ROCKET AF trial, in which rivaroxaban was compared with warfarin in Japanese patients with AF. Two strategies were adopted to quantify the NCB. First, the NCB was calculated as the number of ischemic strokes avoided with anticoagulation minus the number of excess intracranial hemorrhage (ICH) with a weight of 1.5. Second, the composite end point of major bleeding events and secondary efficacy end points (stroke, noncentral nervous system systemic embolism, myocardial infarction and death) to ascertain the NCB were established. Subgroup analysis by CHADS2 score or creatinine clearance was also performed. The adjusted NCB, which was given a weight of 1.5 for ICH, was nominally significant in favor of rivaroxaban therapy (difference in incidence rate -2.13; 95% confidence interval [CI]: -.26 to -3.99). Furthermore, the event rate of the composite end point tended to be lower in patients treated with rivaroxaban than in those treated with warfarin (rivaroxaban: 4.97% per year, warfarin: 6.11% per year; difference in incidence rate: -1.14; 95% CI: -3.40 to 1.12). The event rate of the composite end point tended to be consistently low in patients treated with rivaroxaban in the subanalysis by CHADS2 score and renal function. Analysis of the NCB supports that rivaroxaban therapy provides clinical benefit for Japanese patients with AF. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  16. Warfarin maintenance dose in older patients: higher average dose and wider dose frequency distribution in patients of African ancestry than those of European ancestry.

    Science.gov (United States)

    Garwood, Candice L; Clemente, Jennifer L; Ibe, George N; Kandula, Vijay A; Curtis, Kristy D; Whittaker, Peter

    2010-06-15

    Studies report that warfarin doses required to maintain therapeutic anticoagulation decrease with age; however, these studies almost exclusively enrolled patients of European ancestry. Consequently, universal application of dosing paradigms based on such evidence may be confounded because ethnicity also influences dose. Therefore, we determined if warfarin dose decreased with age in Americans of African ancestry, if older African and European ancestry patients required different doses, and if their daily dose frequency distributions differed. Our chart review examined 170 patients of African ancestry and 49 patients of European ancestry cared for in our anticoagulation clinic. We calculated the average weekly dose required for each stable, anticoagulated patient to maintain an international normalized ratio of 2.0 to 3.0, determined dose averages for groups 80 years of age and plotted dose as a function of age. The maintenance dose in patients of African ancestry decreased with age (PAfrican ancestry required higher average weekly doses than patients of European ancestry: 33% higher in the 70- to 79-year-old group (38.2+/-1.9 vs. 28.8+/-1.7 mg; P=0.006) and 52% in the >80-year-old group (33.2+/-1.7 vs. 21.8+/-3.8 mg; P=0.011). Therefore, 43% of older patients of African ancestry required daily doses >5mg and hence would have been under-dosed using current starting-dose guidelines. The dose frequency distribution was wider for older patients of African ancestry compared to those of European ancestry (PAfrican ancestry indicate that strategies for initiating warfarin therapy based on studies of patients of European ancestry could result in insufficient anticoagulation and thereby potentially increase their thromboembolism risk. Copyright 2010 Elsevier Inc. All rights reserved.

  17. Oral Contraceptives and Cancer Risk

    Science.gov (United States)

    ... Genetics Services Directory Cancer Prevention Overview Research Oral Contraceptives and Cancer Risk On This Page What are oral contraceptives? What is known about the relationship between oral ...

  18. Efficacy and Safety of Apixaban Versus Warfarin in Patients with Atrial Fibrillation and a History of Cancer: Insights from the ARISTOTLE Trial.

    Science.gov (United States)

    Melloni, Chiara; Dunning, Allison; Granger, Christopher B; Thomas, Laine; Khouri, Michel G; Garcia, David A; Hylek, Elaine M; Hanna, Michael; Wallentin, Lars; Gersh, Bernard J; Douglas, Pamela S; Alexander, John H; Lopes, Renato D

    2017-12-01

    Cancer is associated with a prothrombotic state and increases the risk of thrombotic events in patients with atrial fibrillation. We described the clinical characteristics and outcomes and assessed the safety and efficacy of apixaban versus warfarin in patients with atrial fibrillation and cancer in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial. The association between cancer and clinical outcomes was assessed using Cox regression models. At baseline, 1236 patients (6.8%) had a history of cancer; 12.7% had active cancer, and 87.3% had remote cancer. There were no significant associations between history of cancer and stroke/systemic embolism, major bleeding, or death. The effect of apixaban versus warfarin for the prevention of stroke/systemic embolism was consistent among patients with a history of cancer (event/100 patient-years = 1.4 vs 1.2; hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.53-2.26) and no cancer (1.3 vs 1.6; HR, 0.77; 95% CI, 0.64-0.93) (P interaction = .37). The safety and efficacy of apixaban versus warfarin were preserved among patients with and without active cancer. Apixaban was associated with a greater benefit for the composite of stroke/systemic embolism, myocardial infarction, and death in active cancer (HR, 0.30; 95% CI, 0.11-0.83) versus without cancer (HR, 0.86; 95% CI, 0.78-0.95), but not in remote cancer (HR, 1.46; 95% CI, 1.01-2.10) (interaction P = .0028). Cancer was not associated with a higher risk of stroke. The superior efficacy and safety of apixaban versus warfarin were consistent in patients with and without cancer. Our positive findings regarding apixaban use in patients with atrial fibrillation and cancer are exploratory and promising, but warrant further evaluation. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation in Relation to Renal Function Over Time: Insights From the ARISTOTLE Randomized Clinical Trial.

    Science.gov (United States)

    Hijazi, Ziad; Hohnloser, Stefan H; Andersson, Ulrika; Alexander, John H; Hanna, Michael; Keltai, Matyas; Parkhomenko, Alexander; López-Sendón, José L; Lopes, Renato D; Siegbahn, Agneta; Granger, Christopher B; Wallentin, Lars

    2016-07-01

    Renal impairment confers an increased risk of stroke, bleeding, and death in patients with atrial fibrillation. Little is known about the efficacy and safety of apixaban in relation to renal function changes over time. To evaluate changes of renal function over time and their interactions with outcomes during a median of 1.8 years of follow-up in patients with atrial fibrillation randomized to apixaban vs warfarin treatment. The prospective, randomized, double-blind Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) clinical trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Serial creatinine measurements were available in 16 869 patients. Worsening of renal function was defined as an annual decrease in estimated glomerular filtration more than 20%. The relations between treatment, outcomes, and renal function were investigated using Cox regression models, with renal function as a time-dependent covariate. Stroke or systemic embolism (primary outcome), major bleeding (safety outcome), and mortality were examined in relation to renal function over time estimated with both the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations. Among 16 869 patients, the median age was 70 years and 65.2% of patients were men. Worsening in estimated glomerular filtration more than 20% was observed in 2294 patients (13.6%) and was associated with older age and more cardiovascular comorbidities. The risks of stroke or systemic embolism, major bleeding, and mortality were higher in patients with worsening renal function (HR, 1.53; 95% CI, 1.17-2.01 for stroke or systemic embolism; HR, 1.56; 95% CI, 1.27-1.93 for major bleeding; and HR, 2.31; 95% CI, 1.98-2.68 for mortality). The beneficial effects of apixaban vs warfarin on rates of stroke or systemic embolism and major bleeding were consistent in patients with normal or poor renal function over time and also in those with

  20. Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin: insights from the ARISTOTLE trial.

    Science.gov (United States)

    Held, Claes; Hylek, Elaine M; Alexander, John H; Hanna, Michael; Lopes, Renato D; Wojdyla, Daniel M; Thomas, Laine; Al-Khalidi, Hussein; Alings, Marco; Xavier, Dennis; Ansell, Jack; Goto, Shinya; Ruzyllo, Witold; Rosenqvist, Mårten; Verheugt, Freek W A; Zhu, Jun; Granger, Christopher B; Wallentin, Lars

    2015-05-21

    In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban. Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI. Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the

  1. Time Trends of Aspirin and Warfarin Use on Stroke and Bleeding Events in Chinese Patients With New-Onset Atrial Fibrillation.

    Science.gov (United States)

    Guo, Yutao; Wang, Hao; Tian, Yingchun; Wang, Yutang; Lip, Gregory Y H

    2015-07-01

    Much of the clinical epidemiology and treatment patterns for patients with atrial fibrillation (AF) are derived from Western populations. Limited data are available on antithrombotic therapy use over time and its impact on the stroke or bleeding events in newly diagnosed Chinese patients with AF. The present study investigates time trends in warfarin and aspirin use in China in relation to stroke and bleeding events in a Chinese population. We used a medical insurance database involving > 10 million individuals for the years 2001 to 2012 in Yunnan, a southwestern province of China, and performed time-trend analysis on those with newly diagnosed AF. Cox proportional hazards time-varying exposures were used to determine the risk of stroke or bleeding events associated with antithrombotic therapy among patients with AF. Among the randomly sampled 471,446 participants, there were 1,237 patients with AF, including 921 newly diagnosed with AF, thus providing 4,859 person-years of experience (62% men; mean attained age, 70 years). The overall rate of antithrombotic therapy was 37.7% (347 of 921 patients), with 4.1% (38 of 921) on warfarin and 32.3% (298 of 921) on aspirin. Antithrombotic therapy was not related to stroke/bleeding risk scores (CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes, stroke (doubled)] score, P = .522; CHA2DS2-VASc [congestive heart failure, hypertension, age ≥ 75 years (doubled), diabetes mellitus, stroke or transient ischemic attack (doubled), vascular disease, age 65 to 74 years, and female sex] score, P = .957; HAS-BLED [hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly (> 65 years), drugs/alcohol concomitantly] score, P = .095). The use of antithrombotic drugs (mainly aspirin) increased in both women and men over time, with the rate of aspirin increasing from 4.0% in 2007 to 46.1% in 2012 in the former, and from 7.7% in 2007 to 61

  2. Nicotine Oral Inhalation

    Science.gov (United States)

    Nicotine oral inhalation is used to help people stop smoking. Nicotine oral inhalation should be used together with a ... support groups, counseling, or specific behavioral change techniques. Nicotine inhalation is in a class of medications called ...

  3. Oral Cancer Exam

    Medline Plus

    Full Text Available ... Advancing the nation's oral health through research and innovation Health Info Research Grants & Funding Careers & Training News & ... Advancing the nation's oral health through research and innovation Health Info Research Grants & Funding Careers & Training News & ...

  4. Oral Cancer - Multiple Languages

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Oral Cancer URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Oral Cancer - Multiple Languages To use the sharing features on ...

  5. Oral vaccination of fish

    OpenAIRE

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...

  6. Oral Health and Aging

    Science.gov (United States)

    ... of this page please turn JavaScript on. Feature: Oral Health and Aging Oral Health and Aging Past Issues / Summer 2016 Table of ... years. He spoke with NIH MedlinePlus magazine about oral health issues common in older adults. What has been ...

  7. Oral Manifestations of Menopause

    African Journals Online (AJOL)

    manifested in the oral cavity.[9] The teeth and gums are more affected by the hormonal changes occurring before menopause, which decrease the body's ability to fight minor infections or maintain a healthy balance of useful and harmful bacteria within the oral environment.[10] The dentist needs to be aware of oral ...

  8. Oral vaccination of fish

    NARCIS (Netherlands)

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen

  9. Relationship between oral health knowledge, practices and oral ...

    African Journals Online (AJOL)

    Background: Studies have shown that strong knowledge on oral health demonstrates better oral care practice and an association between increased knowledge and better oral health exists. Aim: To assess the influence of oral health knowledge and oral care practices to oral health status of secondary school students in ...

  10. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans ... out more. Oral, Head and Neck Pathology Oral, Head and Neck Pathology Close to 49,750 Americans ...

  11. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed with oral or ... Pathology Oral, Head and Neck Pathology Close to 49,750 Americans will be diagnosed with oral or ...

  12. Oral Health in Rural Communities

    Science.gov (United States)

    ... Guide Rural Health Topics & States Topics View more Oral Health in Rural Communities Adequate access to oral healthcare ... about oral health programs in my area? What oral health disparities are present in rural America? According to ...

  13. Oral Health and Swallowing Problems

    OpenAIRE

    Furuta, Michiko; Yamashita, Yoshihisa

    2013-01-01

    Oral health impacts systemic health. Therefore, oral care is an important consideration in maintaining quality of life (QOL). Previously, maintenance and improvement of oral hygiene was considered essential for achieving oral health. In addition to oral hygiene, oral care in terms of oral function is now considered to maintain QOL. Ingestion of exogenous nutrients via the oral cavity is fundamental to the function of all higher animals, not only human beings. Chewing and swallowing processes ...

  14. Delayed Bleeding and Pelvic Haematoma after Low-Energy Osteoporotic Pubic Rami Fracture in a Warfarin Patient: An Unusual Cause of Abdominal Pain

    Directory of Open Access Journals (Sweden)

    Andrea Sandri

    2014-01-01

    Full Text Available Introduction. Acute abdominal pain may be the presenting symptom in a wide range of diseases in the elderly. Acute abdominal pain related to a delayed bleeding and pelvic haematoma after a low-energy pubic rami fracture is rare and can have important consequences; to the best of our knowledge, only one case has been previously described. Case Report. We present an unusual case of an 83-year-old woman taking warfarin for atrial fibrillation, admitted to the Emergency Department (ED with acute abdominal pain and progressive anemia related to a delayed bleeding and pelvic haematoma 72 hours after a low-energy osteoporotic pubic rami fracture. Warfarin was withheld, anticoagulation was reversed by using fresh frozen plasma and vitamin K, and concentrated red blood cells were given. Haemoglobin level gradually returned to normal with a progressive resorption of the haematoma. Conclusion. Delayed bleeding and pelvic haematoma after osteoporotic pubic rami fracture should be considered in the differential diagnosis of acute abdominal pain in the elderly. This case indicates the need for hospital admission, careful haemodynamic monitoring, and early identification of bleeding in patients with “benign” osteoporotic pubic rami fracture, especially those receiving anticoagulants, to provide an adequate management and prevent severe complications.

  15. Motion of left atrial appendage as a determinant of thrombus formation in patients with a low CHADS2 score receiving warfarin for persistent nonvalvular atrial fibrillation

    Directory of Open Access Journals (Sweden)

    Ono Koji

    2012-12-01

    Full Text Available Abstract Background The aim of this study was to define the independent determinants of left atrial appendage (LAA thrombus among various echocardiographic parameters measured by Velocity Vector Imaging (VVI in patients with nonvalvular atrial fibrillation (AF receiving warfarin, particularly in patients with a low CHADS2 score. Methods LAA emptying fraction (EF and LAA peak longitudinal strain were measured by VVI using transesophageal echocardiography in 260 consecutive patients with nonvalvular persistent AF receiving warfarin. The patients were divided into two groups according to the presence (n=43 or absence (n=217 of LAA thrombus. Moreover, the patients within each group were further divided into subgroups according to a CHADS2 score ≤1. Results Multivariate logistic regression analysis showed that LAAEF was an independent determinant of LAA thrombus in the subgroup of 140 with a low CHADS2 score. Receiver operating characteristics curve analysis showed that an LAAEF of 21% was the optimal cutoff value for predicting LAA thrombus. Conclusions LAA thrombus formation depended on LAA contractility. AF patients with reduced LAA contractile fraction (LAAEF ≤21% require strong anticoagulant therapy to avoid thromboembolic events regardless of a low CHADS2 score (≤1.

  16. Delayed bleeding and pelvic haematoma after low-energy osteoporotic pubic rami fracture in a warfarin patient: an unusual cause of abdominal pain.

    Science.gov (United States)

    Sandri, Andrea; Regis, Dario; Bizzotto, Nicola

    2014-01-01

    Introduction. Acute abdominal pain may be the presenting symptom in a wide range of diseases in the elderly. Acute abdominal pain related to a delayed bleeding and pelvic haematoma after a low-energy pubic rami fracture is rare and can have important consequences; to the best of our knowledge, only one case has been previously described. Case Report. We present an unusual case of an 83-year-old woman taking warfarin for atrial fibrillation, admitted to the Emergency Department (ED) with acute abdominal pain and progressive anemia related to a delayed bleeding and pelvic haematoma 72 hours after a low-energy osteoporotic pubic rami fracture. Warfarin was withheld, anticoagulation was reversed by using fresh frozen plasma and vitamin K, and concentrated red blood cells were given. Haemoglobin level gradually returned to normal with a progressive resorption of the haematoma. Conclusion. Delayed bleeding and pelvic haematoma after osteoporotic pubic rami fracture should be considered in the differential diagnosis of acute abdominal pain in the elderly. This case indicates the need for hospital admission, careful haemodynamic monitoring, and early identification of bleeding in patients with "benign" osteoporotic pubic rami fracture, especially those receiving anticoagulants, to provide an adequate management and prevent severe complications.

  17. Oral steroid contraception.

    Science.gov (United States)

    Sech, Laura A; Mishell, Daniel R

    2015-11-01

    Oral steroid contraception is a popular method of family planning worldwide. Over the past several decades, this method of contraception has changed significantly by decreasing the estrogen dose, changing the progestin component, and reducing the hormone free interval. Despite the popularity of oral steroid contraception, there has been much criticism regarding the associated risks of venous thromboembolism and stroke. Despite these established, yet uncommon risks, oral steroid contraception has many important health benefits. This review highlights the available formulations of oral contraceptives along with their evidence-based associated risks and benefits. Highlights regarding future directions for development of novel oral contraceptives are also addressed.

  18. Essentials of oral cancer.

    Science.gov (United States)

    Rivera, César

    2015-01-01

    Oral cancer is one of the 10 most common cancers in the world, with a delayed clinical detection, poor prognosis, without specific biomarkers for the disease and expensive therapeutic alternatives. This review aims to present the fundamental aspects of this cancer, focused on squamous cell carcinoma of the oral cavity (OSCC), moving from its definition and epidemiological aspects, addressing the oral carcinogenesis, oral potentially malignant disorders, epithelial precursor lesions and experimental methods for its study, therapies and future challenges. Oral cancer is a preventable disease, risk factors and natural history is already being known, where biomedical sciences and dentistry in particular are likely to improve their poor clinical indicators.

  19. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... and Other Oral Surgeries Extractions and Other Oral Surgeries Oral and maxillofacial surgeons surgically treat the soft tissues of the ... and Other Oral Surgeries Extractions and Other Oral Surgeries Oral and maxillofacial surgeons surgically treat the soft tissues of the ...

  20. Warfarin Sodyum Tedavisi Altındaki Protez Mitral Kapaklı Bir Hastada Mallory-Weiss Sendromu ile İlişkili Üst Gastrointestinal Sistem Kanaması

    OpenAIRE

    Yıldız, Banu Şahin; Yılmaz, İbrahim; Aladağ, Nazire Başkurt; Şahin, Alparslan; Yıldız, Mustafa

    2015-01-01

    Mallory-Weiss syndrome refers to bleeding from tears in the mucosa at the junction of the stomach and esophagus. Bleeding has been recognised as the major treatment-limiting complication in patients with prosthetic mitral valve using anticoagulant treatment. We report that upper gastrointestinal system bleeding associated with Mallory-Weiss syndrome in patient with prosthetic mitral valve using warfarin sodium.

  1. Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).

    Science.gov (United States)

    Goodman, Shaun G; Wojdyla, Daniel M; Piccini, Jonathan P; White, Harvey D; Paolini, John F; Nessel, Christopher C; Berkowitz, Scott D; Mahaffey, Kenneth W; Patel, Manesh R; Sherwood, Matthew W; Becker, Richard C; Halperin, Jonathan L; Hacke, Werner; Singer, Daniel E; Hankey, Graeme J; Breithardt, Gunter; Fox, Keith A A; Califf, Robert M

    2014-03-11

    This study sought to report additional safety results from the ROCKET AF (Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation). The ROCKET AF trial demonstrated similar risks of stroke/systemic embolism and major/nonmajor clinically relevant bleeding (principal safety endpoint) with rivaroxaban and warfarin. The risk of the principal safety and component bleeding endpoints with rivaroxaban versus warfarin were compared, and factors associated with major bleeding were examined in a multivariable model. The principal safety endpoint was similar in the rivaroxaban and warfarin groups (14.9 vs. 14.5 events/100 patient-years; hazard ratio: 1.03; 95% confidence interval: 0.96 to 1.11). Major bleeding risk increased with age, but there were no differences between treatments in each age category (<65, 65 to 74, ≥75 years; pinteraction = 0.59). Compared with those without (n = 13,455), patients with a major bleed (n = 781) were more likely to be older, current/prior smokers, have prior gastrointestinal (GI) bleeding, mild anemia, and a lower calculated creatinine clearance and less likely to be female or have a prior stroke/transient ischemic attack. Increasing age, baseline diastolic blood pressure (DBP) ≥90 mm Hg, history of chronic obstructive pulmonary disease or GI bleeding, prior acetylsalicylic acid use, and anemia were independently associated with major bleeding risk; female sex and DBP <90 mm Hg were associated with a decreased risk. Rivaroxaban and warfarin had similar risk for major/nonmajor clinically relevant bleeding. Age, sex, DBP, prior GI bleeding, prior acetylsalicylic acid use, and anemia were associated with the risk of major bleeding. (An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation: NCT00403767

  2. Thromboembolic risks of recombinant factor VIIa Use in warfarin-associated intracranial hemorrhage: a case-control study.

    Science.gov (United States)

    H-Y, Chou Sherry; Xuemei, Cai; G, Konigsberg Rachael; M, Bresette Linda; V, Henderson Galen; A, Sorond Farzaneh; K, Feske Steven

    2012-12-15

    Recombinant factor VIIa (rFVIIa) may be used for rapid hemostasis in life-threatening hemorrhage. In warfarin-associated intracerebral hemorrhage (wICH), FVIIa use is controversial and may carry significant thromboembolic risks. We compared incidence of baseline thromboembolic risk factors and thromboembolism rates in wICH patients treated with additional rFVIIa to those treated with standard therapy of fresh frozen plasma (FFP) and vitamin K alone. We identified 45 consecutive wICH patients treated with additional rFVIIa over 5-year period, and 34 consecutive wICH patients treated with standard therapy alone as comparison group. We compared the incidence of post-hemorrhage cardiac and extra-cardiac thromboembolic complications between two treatment groups, and used logistic regression to adjust for significant confounders such as baseline thromboembolic risk factors. We performed secondary analysis comparing the quantity of FFP transfused between two treatment cohorts. Both rFVIIa-treated and standard therapy-treated wICH patients had a high prevalence of pre-existing thromboembolic diseases including atrial fibrillation (73% vs 68%), deep venous thrombosis (DVT) or pulmonary embolism (PE) (22% vs 18%), coronary artery disease (CAD) (38% vs 32%), and abnormal electrocardiogram (EKG) (78% vs 85%). Troponin elevation following wICH was prevalent in both groups (47% vs 41%). Clinically significant myocardial infarction (MI), defined as troponin > 1.0 ng/dL, occurred in 13% of rFVIIa-treated and 6% of standard therapy-treated patients (p=0.52). Past history of CAD (p=0.0061) and baseline abnormal EKG (p=0.02) were independently associated with clinically significant MI following wICH while rFVIIa use was not. The incidences of DVT/PE (2% vs 9%; p=0.18) and ischemic stroke (2% vs 0%; p=0.38) were similar between two treatment groups. Recombinant FVIIa-treated patients had lower mean INR at 3 (p=0.0001) and 6 hours (ptransfusion (3 vs 5; p=0.003). Pre

  3. Effect of Genetic Variability in the CYP4F2, CYP4F11, and CYP4F12 Genes on Liver mRNA Levels and Warfarin Response

    Directory of Open Access Journals (Sweden)

    J. E. Zhang

    2017-05-01

    Full Text Available Genetic polymorphisms in the gene encoding cytochrome P450 (CYP 4F2, a vitamin K oxidase, affect stable warfarin dose requirements and time to therapeutic INR. CYP4F2 is part of the CYP4F gene cluster, which is highly polymorphic and exhibits a high degree of linkage disequilibrium, making it difficult to define causal variants. Our objective was to examine the effect of genetic variability in the CYP4F gene cluster on expression of the individual CYP4F genes and warfarin response. mRNA levels of the CYP4F gene cluster were quantified in human liver samples (n = 149 obtained from a well-characterized liver bank and fine mapping of the CYP4F gene cluster encompassing CYP4F2, CYP4F11, and CYP4F12 was performed. Genome-wide association study (GWAS data from a prospective cohort of warfarin-treated patients (n = 711 was also analyzed for genetic variations across the CYP4F gene cluster. In addition, SNP-gene expression in human liver tissues and interactions between CYP4F genes were explored in silico using publicly available data repositories. We found that SNPs in CYP4F2, CYP4F11, and CYP4F12 were associated with mRNA expression in the CYP4F gene cluster. In particular, CYP4F2 rs2108622 was associated with increased CYP4F2 expression while CYP4F11 rs1060467 was associated with decreased CYP4F2 expression. Interestingly, these CYP4F2 and CYP4F11 SNPs showed similar effects with warfarin stable dose where CYP4F11 rs1060467 was associated with a reduction in daily warfarin dose requirement (∼1 mg/day, Pc = 0.017, an effect opposite to that previously reported with CYP4F2 (rs2108622. However, inclusion of either or both of these SNPs in a pharmacogenetic algorithm consisting of age, body mass index (BMI, gender, baseline clotting factor II level, CYP2C9∗2 rs1799853, CYP2C9∗3 rs1057910, and VKORC1 rs9923231 improved warfarin dose variability only by 0.5–0.7% with an improvement in dose prediction accuracy of ∼1–2%. Although there is complex

  4. Improving oral health and oral health care delivery for children.

    Science.gov (United States)

    Crall, James J

    2011-02-01

    National and state-level evidence has documented ongoing disparities in children's health and utilization of oral health care services, prompting a re-examination of factors associated with poor oral health and low use of oral health services. These efforts have yielded a wide array of proposals for improving children's oral health and oral health care delivery. This paper offers a perspective on the current context of efforts to improve children's oral health and oral health care delivery.

  5. Clinical trials with new oral anticoagulants. Additive value of indirect comparisons also named network meta-analyses.

    Science.gov (United States)

    Harenberg, J; Weiss, C

    2013-01-01

    To compare the efficacy and safety of the new oral anticoagulants (NOAC), ideally head-to-head clinical trials should be performed. Given the expense of such an undertaking, it is highly unlikely that such a comparison would be performed. Therefore, there is a need for an unbiased comparative assessment of the benefits and risks of the NOACs, based on the available trial data. Indirect or mixed treatment comparisons may be an useful tool to overcome these limitations also known as network meta-analysis (NMA). The aim of this paper is to give an overview on published NMAs for dabigatran, rivaroxaban and apixaban, each assessed against warfarin in patients with atrial fibrillation, and against enoxaparin in patients undergoing total knee and total hip replacement surgery, in order to obtain insights into the comparability of the adopted methodological techniques.

  6. Fitting the right non-vitamin K antagonist oral anticoagulant to the right patient with non-valvular atrial fibrillation

    DEFF Research Database (Denmark)

    Li, Yanguang; Pastori, Daniele; Lip, Gregory YH

    2018-01-01

    Atrial fibrillation (AF) is the most prevalent arrhythmia and is associated with an increased risk of ischemic stroke (IS) and systemic embolism (SE). Stroke prevention is a key element for the overall management of AF patients. The non-vitamin K antagonist oral anticoagulants (NOACs......), such as dabigatran, rivaroxaban, apixaban and edoxaban, are at least as effective as warfarin in reducing IS/SE with a lower rate of major bleeding. Various analyses from the large Phase III randomised trials demonstrated different efficacy and safety of NOACs in specific subgroups of patients. The randomised trials...... are supplemented by effectiveness and safety data from real world observational cohorts following the availability of these drugs for use in everyday clinical practice. Given the clinical heterogeneity of AF patients, the available data from trials and real-world studies allow us to fit the right NOAC...

  7. The vitamin K-dependent carboxylation system in human osteosarcoma U2-OS cells. Antidotal effect of vitamin K1 and a novel mechanism for the action of warfarin.

    Science.gov (United States)

    Wallin, R; Rossi, F; Loeser, R; Key, L L

    1990-01-01

    An osteoblast-like human osteosarcoma cell line (U2-OS) has been shown to possess a vitamin K-dependent carboxylation system which is similar to the system in human HepG2 cells and in liver and lung from the rat. In an 'in vitro' system prepared from these cells, vitamin K1 was shown to overcome warfarin inhibition of gamma-carboxylation carried out by the vitamin K-dependent carboxylase. The data suggest that osteoblasts, the cells involved in synthesis of vitamin K-dependent proteins in bone, can use vitamin K1 as an antidote to warfarin poisoning if enough vitamin K1 can accumulate in the tissue. Five precursors of vitamin K-dependent proteins were identified in osteosarcoma and HepG2 cells respectively. In microsomes (microsomal fractions) from the osteosarcoma cells these precursors revealed apparent molecular masses of 85, 78, 56, 35 and 31 kDa. When osteosarcoma cells were cultured in the presence of warfarin, vitamin K-dependent 14C-labelling of the 78 kDa precursor was enhanced. Selective 14C-labelling of one precursor was also demonstrated in microsomes from HepG2 cells and from rat lung after warfarin treatment. In HepG2 cells this precursor was identified as the precursor of (clotting) Factor X. This unique 14C-labelling pattern of precursors of vitamin K-dependent proteins in microsomes from different cells and tissues reflects a new mechanism underlying the action of warfarin. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:2386486

  8. Contributions of procoagulants and anticoagulants to the international normalized ratio and thrombin generation assay in patients treated with warfarin: potential role of protein Z as a powerful determinant of coagulation assays.

    Science.gov (United States)

    Choi, Qute; Kim, Ji-Eun; Hyun, Jungwon; Han, Kyou-Sup; Kim, Hyun Kyung

    2013-07-01

    The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them. The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured. The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0-3.0 was 290.1-494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro. The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. VKORC1-1639G>A, CYP2C9, EPHX1691A>G genotype, body weight, and age are important predictors for warfarin maintenance doses in patients with mechanical heart valve prostheses in southwest China.

    Science.gov (United States)

    Gu, Qiang; Kong, Yan; Schneede, Jörn; Xiao, Ying-Bin; Chen, Lin; Zhong, Qian-Jin; Wang, Xue-Feng; Hao, Jia; Chen, Bai-Cheng; Chen, Jing-Jin

    2010-12-01

    To investigate the contribution of genetic polymorphisms of vitamin K epoxide reductase complex subunit 1 gene VKORC1-1639G>A, cytochrome P450 2C9 gene (CYP2C9), EPHXI, and clinical factors to warfarin sensitivity in southwest Chinese Han patients with mechanical heart valve prostheses. A total of 127 patients with mechanical heart valve prostheses who have been followed up at our department during the past 23 years were enrolled in this study and compared to a control group that consisted of 133 randomly selected healthy blood donors. These Chinese patients met stable warfarin dosage requirements and had reached the target international normalized ratio (INR) of 1.5-2.0. PCR and direct sequencing were carried out to identify the polymorphisms of VKORC1-1639G>A (rs9923231), CYP2C9*3 (rs1057910), CYP2C9 IVS3-65G>C (rs9332127), and EPHX1691A>G (rs4653436). In addition, total and free (non-protein-bound) warfarin concentrations were analyzed. There were great interindividual differences in warfarin maintenance dosage (ranging from 0.6 to 8.4 mg/day) among the 127 patients with mechanical heart valve prostheses. VKORC1-1639G>A, CYP2C9, EPHX1691A>G polymorphism, body weight, and age were found to affect the dose demands. Multiple linear regression models incorporating genetic polymorphisms of VKORC1, CYP2C9, EPHX1691A>G, and the nongenetic factors of age and body weight were developed, and explained up to 76.8% of the total variation (adjusted R (2) of 0.743) in warfarin maintenance doses in southwest Chinese patients with mechanical heart valve prostheses.

  10. No Effect of Omega-3 Carboxylic Acids on Pharmacokinetics/Pharmacodynamics of Warfarin or on Platelet Function When Co-administered with Acetylsalicylic Acid: Results of Two Phase I Studies in Healthy Volunteers.

    Science.gov (United States)

    Offman, Elliot; Davidson, Michael; Nilsson, Catarina

    2017-06-01

    Omega-3 carboxylic acids (OM3-CA) can lower triglyceride levels. Our objective was to assess the effects of OM3-CA on warfarin pharmacokinetics and pharmacodynamics and on acetylsalicylic acid (ASA)-dependent and independent platelet activation when co-administered with ASA in two phase I studies. In ECLIPSE II (NCT01431690), 26 participants received warfarin 25 mg on days 1 and 22 and OM3-CA 4 g once daily from day 8 to day 28. In OM-EPA-007 (NCT01486433), 52 participants received simvastatin 40 mg plus ASA 81 mg once daily for 14 days, with or without OM3-CA 4 g. Lack of a drug-drug interaction was indicated when 90% confidence intervals (CIs) fell entirely within the range 80-125% for least-squares mean (LSM) ratios of area under the concentration-time curve (AUC), maximum observed plasma concentration (C max ), international normalized ratio (INR) AUC to 168 h and maximum INR. In ECLIPSE II, 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for AUC and C max of S- and R-warfarin enantiomers. The 90% CIs for LSM ratios of with:without OM3-CA fell within 80-125% for INR AUC to 168 h after dosing and for maximum INR of warfarin. In OM-EPA-007, no significant effect of OM3-CA was observed on ASA-dependent or ASA-independent platelet activation. No deaths or serious adverse events occurred in either study. OM3-CA did not affect the pharmacokinetics or pharmacodynamics of warfarin or the pharmacodynamic effects of ASA. OM3-CA did not affect platelet function when co-administered with ASA.

  11. Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy: Endoscopic findings, clinical management and outcome

    Science.gov (United States)

    Thomopoulos, Konstantinos C; Mimidis, Konstantinos P; Theocharis, George J; Gatopoulou, Anthie G; Kartalis, Georgios N; Nikolopoulou, Vassiliki N

    2005-01-01

    AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P = 0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied. PMID:15761977

  12. Radiation induced oral mucositis

    Directory of Open Access Journals (Sweden)

    P S Satheesh Kumar

    2009-01-01

    Full Text Available Patients receiving radiotherapy or chemotherapy will receive some degree of oral mucositis The incidence of oral mucositis was especially high in patients: (i With primary tumors in the oral cavity, oropharynx, or nasopharynx; (ii who also received concomitant chemotherapy; (iii who received a total dose over 5,000 cGy; and (iv who were treated with altered fractionation radiation schedules. Radiation-induced oral mucositis affects the quality of life of the patients and the family concerned. The present day management of oral mucositis is mostly palliative and or supportive care. The newer guidelines are suggesting Palifermin, which is the first active mucositis drug as well as Amifostine, for radiation protection and cryotherapy. The current management should focus more on palliative measures, such as pain management, nutritional support, and maintenance, of good oral hygiene

  13. Utilization of Oral Anticoagulation in a Teaching Hospital in Nigeria

    African Journals Online (AJOL)

    : Anticoagulation, Barriers, Nigeria, .... Cardiovascular disease (thromboembolic stroke). 2/26 (7.7). Heart valve replacement. 2/26 (7.7) ... accounts for approximately 2% of the reported hemorrhagic complications of warfarin therapy and is ...

  14. African Journal of Oral Health Sciences

    African Journals Online (AJOL)

    The African Journal of Oral Health Sciences is devoted to research into oral diseases and encourages a multidisciplinary approach. Emphasis is on oral pathology, oral microbiology, oral medicine, oral physiology and biochemistry and related clinical sciences.

  15. Towards understanding oral health.

    Science.gov (United States)

    Zaura, Egija; ten Cate, Jacob M

    2015-01-01

    During the last century, dental research has focused on unraveling the mechanisms behind various oral pathologies, while oral health was typically described as the mere absence of oral diseases. The term 'oral microbial homeostasis' is used to describe the capacity of the oral ecosystem to maintain microbial community stability in health. However, the oral ecosystem itself is not stable: throughout life an individual undergoes multiple physiological changes while progressing through infancy, childhood, adolescence, adulthood and old age. Recent discussions on the definition of general health have led to the proposal that health is the ability of the individual to adapt to physiological changes, a condition known as allostasis. In this paper the allostasis principle is applied to the oral ecosystem. The multidimensionality of the host factors contributing to allostasis in the oral cavity is illustrated with an example on changes occurring in puberty. The complex phenomenon of oral health and the processes that prevent the ecosystem from collapsing during allostatic changes in the entire body are far from being understood. As yet individual components (e.g. hard tissues, microbiome, saliva, host response) have been investigated, while only by consolidating these and assessing their multidimensional interactions should we be able to obtain a comprehensive understanding of the ecosystem, which in turn could serve to develop rational schemes to maintain health. Adapting such a 'system approach' comes with major practical challenges for the entire research field and will require vast resources and large-scale multidisciplinary collaborations. 2015 S. Karger AG, Basel

  16. Global Oral Health Inequalities

    Science.gov (United States)

    Garcia, I.; Tabak, L.A.

    2011-01-01

    Despite impressive worldwide improvements in oral health, inequalities in oral health status among and within countries remain a daunting public health challenge. Oral health inequalities arise from a complex web of health determinants, including social, behavioral, economic, genetic, environmental, and health system factors. Eliminating these inequalities cannot be accomplished in isolation of oral health from overall health, or without recognizing that oral health is influenced at multiple individual, family, community, and health systems levels. For several reasons, this is an opportune time for global efforts targeted at reducing oral health inequalities. Global health is increasingly viewed not just as a humanitarian obligation, but also as a vehicle for health diplomacy and part of the broader mission to reduce poverty, build stronger economies, and strengthen global security. Despite the global economic recession, there are trends that portend well for support of global health efforts: increased globalization of research and development, growing investment from private philanthropy, an absolute growth of spending in research and innovation, and an enhanced interest in global health among young people. More systematic and far-reaching efforts will be required to address oral health inequalities through the engagement of oral health funders and sponsors of research, with partners from multiple public and private sectors. The oral health community must be “at the table” with other health disciplines and create opportunities for eliminating inequalities through collaborations that can harness both the intellectual and financial resources of multiple sectors and institutions. PMID:21490232

  17. Taking warfarin (Coumadin)

    Science.gov (United States)

    ... PA: Elsevier Saunders; 2014:chap 35. Kager L, Evans WE. Pharmacogenomics and hematologic diseases. In: Hoffman R, ... A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. is among ...

  18. Oral Microbiology and Immunology

    DEFF Research Database (Denmark)

    Dahlén, Gunnar; Fiehn, Nils-Erik; Olsen, Ingar

    , dental assistants and trainees may find it a useful source of reference. The contents are based on general microbiology and immunology. Oral microbiology is given particular attention, with examples relevant to oral infectious diseases. Each chapter opens with a relatively short pre-reading section...

  19. Shared Oral Care

    DEFF Research Database (Denmark)

    Hede, Børge; Elmelund Poulsen,, Johan; Christophersen, Rasmus

    2014-01-01

    Shared Oral Care - Forebyggelse af orale sygdomme på plejecentre Introduktion og formål: Mangelfuld mundhygiejne hos plejekrævende ældre er et alment og veldokumenteret sundhedsproblem, der kan føre til massiv udvikling af tandsygdomme, og som yderligere kan være medvirkende årsag til alvorlige...

  20. Prodrug for bioreductive activation-independent delivery of menahydroquinone-4: human liver enzymatic activation and its action in warfarin-poisoned human liver.

    Science.gov (United States)

    Takata, J; Karube, Y; Hanada, M; Matsunaga, K; Iwasaki, H

    1999-02-01

    The N,N-dimethylglycine esters of menahydroquinone-4 (1-mono, 1; 4-mono, 2; 1,4-bis, 3) were established in previous reports as prodrugs that could achieve the systemic bioreductive activation-independent delivery of menahydroquinone-4 (MKH), the active form of menaquinone-4 (MK-4), in rat. The present study was undertaken to investigate if the prodrugs could undergo cleavage to parent drug (MKH) by a human tissues enzyme catalyzed hydrolytic pathway, the mechanism of the prodrugs for vitamin K-dependent carboxylation in human liver and their action in the warfarin poisoned human liver. The hydrolysis of the esters was shown to be catalyzed by esterases located in human liver but not in human plasma. The susceptibility of the esters to undergo human liver esterase hydrolysis was affected by the esterified position: 1>2>3. By using a human liver microsomal test system, the stimulation of vitamin K-dependent carboxylation with the prodrugs was determined. The prodrug could stimulate the carboxylation activity in the absence of dithiothreitol, an artificial activator of the reductive activation pathway of MK-4. The carboxylation activity of the prodrug was strongly inhibited in the presence of eserine, an esterase inhibitor. The prodrug could also stimulate the carboxylase under warfarin-poisoned conditions, where the vitamin K cycle was strongly inhibited. The results confirmed that the prodrug could generate MKH in human liver (active site), and that the resultant MKH could act as a cofactor for the carboxylase without reductive activation processes of MK-4 to MKH. Such bioreductive activation-independent vitamin K-dependent carboxylation characteristic of the prodrug leads to enhanced pharmacological efficacy in the treatment of hypoprothrombinaemia induced in patients with coumarin and cephalosporin therapies.

  1. Evaluation of a pharmacogenetic-based warfarin dosing algorithm in patients with low time in therapeutic range - study protocol for a randomized controlled trial.

    Science.gov (United States)

    Marcatto, Leiliane Rodrigues; Sacilotto, Luciana; Bueno, Carolina Tosin; Facin, Mirella; Strunz, Celia Maria Cassaro; Darrieux, Francisco Carlos Costa; Scanavacca, Maurício Ibrahim; Krieger, Jose Eduardo; Pereira, Alexandre Costa; Santos, Paulo Caleb Junior Lima

    2016-11-17

    Time in therapeutic range (TTR) is a measurement of quality of warfarin therapy and lower TTR values (algorithm specifically calibrated for a Brazilian patient sample. The aims of this study are: to evaluate the impact of a genetic-based algorithm, compared to traditional anticoagulation, in the time to achieve the therapeutic target and in TTR percentage; and to assess the cost-effectiveness of genotype-guided warfarin dosing in a specific cohort of patients with low TTR (algorithm will be used. At the second, third, fourth and fifth consultations (with an interval of 7 days each) INR will be measured and, if necessary, the dose will be adjusted based on guidelines. Afterwards, patients who are INR stable will begin measuring their INR in 30 day intervals; if the patient's INR is not stable, the patient will return in 7 days for a new measurement of the INR. Outcomes measures will include the time to achieve the therapeutic target and the percentage of TTR at 4 and 12 weeks. In addition, as a secondary end-point, pharmacoeconomic analysis will be carried out. Ethical approval was granted by the Ethics Committee for Medical Research on Human Beings of the Clinical Hospital of the University of São Paulo Medical School. This randomized study will include patients with low TTR and it will evaluate whether a population-specific genetic algorithm might be more effective than traditional anticoagulation for a selected group of poorly anticoagulated patients. ClinicalTrials.gov, NCT02592980 . Registered on 29 October 2015.

  2. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Oral Surgeries Facial Cosmetic Surgery Facial Injury / Trauma Surgery Obstructive Sleep Apnea (OSA) Oral, Head and Neck Pathology TMJ and Facial Pain Wisdom Teeth Management Procedures Anesthesia Anesthesia Oral and maxillofacial surgeons are ...

  3. Head, Neck, and Oral Cancer

    Medline Plus

    Full Text Available ... Other Oral Surgeries Facial Cosmetic Surgery Facial Injury / Trauma Surgery Obstructive Sleep Apnea (OSA) Oral, Head and Neck Pathology TMJ and Facial Pain Wisdom Teeth Management Procedures Anesthesia Anesthesia Oral and maxillofacial surgeons ...

  4. What Is an Oral Piercing?

    Science.gov (United States)

    ... to your desktop! more... What Is an Oral Piercing? Article Chapters What Is an Oral Piercing? print full article print this chapter email this article Oral piercing can cause pain, swelling, infection, drooling, taste loss, ...

  5. American Academy of Oral Medicine

    Science.gov (United States)

    ... Statements Newsletters AAOM: Representing the Discipline of Oral Medicine Oral Medicine is the discipline of dentistry concerned with the ... offers credentialing, resources and professional community for oral medicine practitioners. Our membership provides care to thousands. We ...

  6. Literatura Oral Hispanica (Hispanic Oral Literature).

    Science.gov (United States)

    McAlpine, Dave

    As part of a class in Hispanic Oral Literature, students collected pieces of folklore from various Hispanic residents in the region known as "Siouxland" in Iowa. Consisting of some of the folklore recorded from the residents, this paper includes 18 "cuentos y leyendas" (tales and legends), 48 "refranes" (proverbs), 17…

  7. Randomized controlled trial of supervised patient self-testing of warfarin therapy using an internet-based expert system.

    LENUS (Irish Health Repository)

    Ryan, F

    2009-08-01

    Increased frequency of prothrombin time testing, facilitated by patient self-testing (PST) of the International Normalized Ratio (INR) can improve the clinical outcomes of oral anticoagulation therapy (OAT). However, oversight of this type of management is often difficult and time-consuming for healthcare professionals. This study reports the first randomized controlled trial of an automated direct-to-patient expert system, enabling remote and effective management of patients on OAT.

  8. Examining the association between oral health and oral HPV infection.

    Science.gov (United States)

    Bui, Thanh Cong; Markham, Christine M; Ross, Michael Wallis; Mullen, Patricia Dolan

    2013-09-01

    Oral human papillomavirus (HPV) infection is the cause of 40% to 80% of oropharyngeal cancers; yet, no published study has examined the role of oral health in oral HPV infection, either independently or in conjunction with other risk factors. This study examined the relation between oral health and oral HPV infection and the interactive effects of oral health, smoking, and oral sex on oral HPV infection. Our analyses comprised 3,439 participants ages 30 to 69 years for whom data on oral HPV and oral health were available from the nationally representative 2009-2010 National Health and Nutrition Examination Survey. Results showed that higher unadjusted prevalence of oral HPV infection was associated with four measures of oral health, including self-rated oral health as poor-to-fair [prevalence ratio (PR) = 1.56; 95% confidence interval (CI), 1.25-1.95], indicated the possibility of gum disease (PR = 1.51; 95% CI, 1.13-2.01), reported use of mouthwash to treat dental problems in the past week (PR = 1.28; 95% CI, 1.07-1.52), and higher number of teeth lost (Ptrend = 0.035). In multivariable logistic regression models, oral HPV infection had a statistically significant association with self-rated overall oral health (OR = 1.55; 95% CI, 1.15-2.09), independent of smoking and oral sex. In conclusion, poor oral health was an independent risk factor of oral HPV infection, irrespective of smoking and oral sex practices. Public health interventions may aim to promote oral hygiene and oral health as an additional measure to prevent HPV-related oral cancers.

  9. Prevention of gingival trauma : Oral hygiene devices and oral piercings

    NARCIS (Netherlands)

    Hoenderdos, N.L.

    2017-01-01

    Maintaining healthy teeth and soft oral tissues for life is important. Oral hygiene devices and oral piercings can damage the soft oral tissues. This thesis investigates the safety of manual toothbrushes, interdental brushes and rubber bristles interdental cleaners by analysing the gingival abrasion

  10. Association between CYP4F2 genotype and circulating plasma vitamin K concentration in children on chronic warfarin therapy: Possible long-term implications for bone development and vascular health.

    Science.gov (United States)

    Kampouraki, Emmanouela; Avery, Peter J; Biss, Tina; Kamali, Farhad

    2017-12-01

    Vitamin K is essential, for the activation of clotting proteins, as well as the biosynthesis of osteocalcin in bones and the activation of matrix-Gla protein needed in maintaining vasculature health. Cytochrome p450 4F2 (CYP4F2) enzyme is involved in vitamin K catabolism. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability. We show that children on chronic warfarin therapy have low levels of vitamin K and vitamin K levels are linked to CYP4F2 genotype. Long-term low levels of vitamin K, influenced by CYP4F2 genotype, might affect bone development and vascular health in children on chronic warfarin therapy. © 2017 Wiley Periodicals, Inc.

  11. Amiloidosis oral nodular Oral nodular amyloidosis

    Directory of Open Access Journals (Sweden)

    P. Martos Díaz

    2008-02-01

    Full Text Available Introducción. La amiloidosis constituye una entidad marcada por el depósito de amiloide en diferentes tejidos. En la cavidad oral se manifiesta habitualmente en forma de macroglosia, y más raramente, como nódulos dispuestos en la superficie. Caso clínico. Varón afecto de Mieloma Múltiple, que comienza con lesiones nodulares en labio inferior y lengua. A raíz de estas lesiones, mediante estudio histológico, es diagnosticado de Amiloidosis Sistémica. Discusión. Los nódulos amiloideos en la cavidad oral, constituyen una manifestación rara de la amiloidosis sistémica. Su aparición conlleva la necesidad de realizar un diagnostico diferencial con otras entidades y el diagnostico de certeza se obtiene mediante el análisis histológico.Introduction. Amyloidosis is a condition characterized by the deposit of amyloid in different tissues. In the oral cavity it is usually manifested as macroglossia and, more rarely, as nodules on the surface. Clinical case. A man had multiple myeloma that began with nodular lesions of the lower lip and tongue. As a result of these lesions, the patient was diagnosed of systemic amyloidosis by histological study. Discussion. Amyloid nodules in the oral cavity are a rare manifestation of systemic amyloidosis. Its appearance entails the necessity to make I diagnose differential with other organizations and I diagnose of certainty is obtained by means of the histological analysis.

  12. Oral Cancer Exam

    Medline Plus

    Full Text Available ... to NIDCR Contact Us Home Health Info Health Information The Oral Cancer Exam See a step-by- ... National Institutes of Health in Bethesda, Md. This information is not copyrighted. Make as many copies as ...

  13. Ipratropium Oral Inhalation

    Science.gov (United States)

    Ipratropium oral inhalation is used to prevent wheezing, shortness of breath, coughing, and chest tightness in people with chronic obstructive pulmonary disease (COPD; a group of diseases that affect the lungs and airways) such as chronic bronchitis (swelling of ...

  14. Oral Appliances Therapy

    Science.gov (United States)

    ... is an effective treatment option for snoring and obstructive sleep apnea (OSA). A custom-fit oral sleep appliance can improve your sleep, restore your alertness and revitalize your health. Here is a guide to help you get ...

  15. [Oral precancer and cancer].

    Science.gov (United States)

    López-López, José; Omaña-Cepeda, Carlos; Jané-Salas, Enric

    2015-11-06

    We reviewed the concept of oral precancerous lesions, oral cancer, and the possibility of early diagnosis. With the keywords: premalignant oral lesions prevention, a search was performed over the past 10 years. Also clinical trials are searched from January 2011 until today with the keywords: oral cancer prevention AND dentistry. It is emphasized that there can be no significant changes related to the concept of precancerous lesions and cancer, and those relating to the early diagnosis. Despite the numerous described methods of screening, biopsy remains the most useful test, and therefore it is essential, mainly if we consider the new possibilities of molecular studies. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. Cromolyn Oral Inhalation

    Science.gov (United States)

    ... your doctor.Cromolyn oral inhalation helps to prevent asthma attacks (sudden episodes of shortness of breath, wheezing, and coughing) but will not stop an asthma attack that has already started. Your doctor will prescribe ...

  17. Fostering oral presentation performance

    NARCIS (Netherlands)

    Ginkel, van Stan; Gulikers, Judith; Biemans, Harm; Mulder, Martin

    2017-01-01

    Previous research revealed significant differences in the effectiveness of various feedback sources for encouraging students’ oral presentation performance. While former studies emphasised the superiority of teacher feedback, it remains unclear whether the quality of feedback actually differs

  18. Oral Cancer Foundation

    Science.gov (United States)

    ... 14T22:05:33+00:00 October, 2016 | This last weekend the OCF 3rd Annual Southern California Oral Cancer Walk for Awareness took place in Fountain Valley at Mile Square Park. The walk is a little different ...

  19. Intravenous versus oral etoposide

    DEFF Research Database (Denmark)

    Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.

    2018-01-01

    High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

  20. Oral vs. salivary diagnostics

    Science.gov (United States)

    Marques, Joana; Corby, Patricia M.; Barber, Cheryl A.; Abrams, William R.; Malamud, Daniel

    2015-05-01

    The field of "salivary diagnostics" includes studies utilizing samples obtained from a variety of sources within the oral cavity. These samples include; whole unstimulated saliva, stimulated whole saliva, duct saliva collected directly from the parotid, submandibular/sublingual glands or minor salivary glands, swabs of the buccal mucosa, tongue or tonsils, and gingival crevicular fluid. Many publications state "we collected saliva from subjects" without fully describing the process or source of the oral fluid. Factors that need to be documented in any study include the time of day of the collection, the method used to stimulate and collect the fluid, and how much fluid is being collected and for how long. The handling of the oral fluid during and post-collection is also critical and may include addition of protease or nuclease inhibitors, centrifugation, and cold or frozen storage prior to assay. In an effort to create a standard protocol for determining a biomarker's origin we carried out a pilot study collecting oral fluid from 5 different sites in the mouth and monitoring the concentrations of pro- and anti-inflammatory cytokines detected using MesoScaleDiscovery (MSD) electrochemiluminesence assays. Our data suggested that 3 of the cytokines are primarily derived from the submandibular gland, while 7 of the cytokines come from a source other than the major salivary glands such as the minor salivary glands or cells in the oral mucosae. Here we review the literature on monitoring biomarkers in oral samples and stress the need for determining the blood/saliva ratio when a quantitative determination is needed and suggest that the term oral diagnostic be used if the source of an analyte in the oral cavity is unknown.

  1. Immunologically mediated oral diseases

    OpenAIRE

    Jimson, Sudha; Balachader, N.; Anita, N.; Babu, R.

    2015-01-01

    Immune mediated diseases of oral cavity are uncommon. The lesions may be self-limiting and undergo remission spontaneously. Among the immune mediated oral lesions the most important are lichen planus, pemphigus, erythema multiformi, epidermolysis bullosa, systemic lupus erythematosis. Cellular and humoral mediated immunity play a major role directed against epithelial and connective tissue in chronic and recurrent patterns. Confirmatory diagnosis can be made by biopsy, direct and indirect imm...

  2. ON ORAL CANCER

    Directory of Open Access Journals (Sweden)

    P. V. Svetitsky

    2012-01-01

    Full Text Available The paper analyzes a rise in the incidence of oral cancer in the Rostov Region since the 1990s. The study has indicated that this rise is associated with regional population growth due to the forced migrants after the collapse of the USSR. Financial problems, unbalanced nutrition, poor oral hygiene, and depression in this group of patients have contributed to the higher incidence of precancers and cancers.

  3. Diabetes and oral health

    OpenAIRE

    Kjersti Skjold Rønningen; Morten Enersen

    2012-01-01

    Background: Diabetes describes a group of disorders characterized by elevated levels of glucose in the blood and abnormalities of carbohydrate, fat and protein metabolism. A number of oral diseases and disorders have been associated with diabetes, and periodontitis has been identified as a possible risk factor for poor metabolic control in subjects with diabetes.Methods: This paper reviews the scientific literature to identify oral conditions that have been proposed and are known to be affect...

  4. Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes.

    Science.gov (United States)

    Hylek, Elaine M; Held, Claes; Alexander, John H; Lopes, Renato D; De Caterina, Raffaele; Wojdyla, Daniel M; Huber, Kurt; Jansky, Petr; Steg, Philippe Gabriel; Hanna, Michael; Thomas, Laine; Wallentin, Lars; Granger, Christopher B

    2014-05-27

    This study sought to characterize major bleeding on the basis of the components of the major bleeding definition, to explore major bleeding by location, to define 30-day mortality after a major bleeding event, and to identify factors associated with major bleeding. Apixaban was shown to reduce the risk of major hemorrhage among patients with atrial fibrillation in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. All patients who received at least 1 dose of a study drug were included. Major bleeding was defined according to the criteria of the International Society on Thrombosis and Haemostasis. Factors associated with major hemorrhage were identified using a multivariable Cox model. The on-treatment safety population included 18,140 patients. The rate of major hemorrhage among patients in the apixaban group was 2.13% per year compared with 3.09% per year in the warfarin group (hazard ratio [HR] 0.69, 95% confidence interval [CI]: 0.60 to 0.80; p < 0.001). Compared with warfarin, major extracranial hemorrhage associated with apixaban led to reduced hospitalization, medical or surgical intervention, transfusion, or change in antithrombotic therapy. Major hemorrhage followed by mortality within 30 days occurred half as often in apixaban-treated patients than in those receiving warfarin (HR 0.50, 95% CI: 0.33 to 0.74; p < 0.001). Older age, prior hemorrhage, prior stroke or transient ischemic attack, diabetes, lower creatinine clearance, decreased hematocrit, aspirin therapy, and nonsteroidal anti-inflammatory drugs were independently associated with an increased risk. Apixaban, compared with warfarin, was associated with fewer intracranial hemorrhages, less adverse consequences following extracranial hemorrhage, and a 50% reduction in fatal consequences at 30 days in cases of major hemorrhage. Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  5. Oral sex and oral health: An enigma in itself

    OpenAIRE

    Kumar, Tarun; Puri, Gagan; Aravinda, Konidena; Arora, Neha; Patil, Deepa; Gupta, Rajesh

    2015-01-01

    Oral sex is commonly practiced by sexually active couples of various age groups, including male-female and same-gender adolescents. The various type of oral sex practices are fellatio, cunnilingus, and analingus. Oral sex can transmit oral, respiratory, and genital infections from one site in body to the other. Oral health has a direct correlation on the transmission of infection; a cut in the mouth, bleeding gums, lip sores or broken skin increases chances of life-threatening infections. Alt...

  6. Oral microbiome and oral and gastrointestinal cancer risk

    OpenAIRE

    Ahn, Jiyoung; Chen, Calvin Y.; Hayes, Richard B.

    2012-01-01

    A growing body of evidence implicates human oral bacteria in the etiology of oral and gastrointestinal cancers. Epidemiological studies consistently report increased risks of these cancers in men and women with periodontal disease or tooth loss, conditions caused by oral bacteria. More than 700 bacterial species inhabit the oral cavity, including at least 11 bacterial phyla and 70 genera. Oral bacteria may activate alcohol and smoking-related carcinogens locally or act systemically, through c...

  7. Prevention of gingival trauma: Oral hygiene devices and oral piercings

    OpenAIRE

    Hoenderdos, N.L.

    2017-01-01

    Maintaining healthy teeth and soft oral tissues for life is important. Oral hygiene devices and oral piercings can damage the soft oral tissues. This thesis investigates the safety of manual toothbrushes, interdental brushes and rubber bristles interdental cleaners by analysing the gingival abrasion score. The efficacy of the various oral hygiene devices is measured by the use of dental plaque scores and gingivitis scores. In addition, the prevalence, the short- and long-term effects and the ...

  8. Determinants of Oral Health: Does Oral Health Literacy Matter?

    OpenAIRE

    Naghibi Sistani, Mohammad Mehdi; Yazdani, Reza; Virtanen, Jorma; Pakdaman, Afsaneh; Murtomaa, Heikki

    2013-01-01

    Objective. To evaluate oral health literacy, independent of other oral health determinants, as a risk indicator for self-reported oral health. Methods. A cross-sectional population-based survey conducted in Tehran, Iran. Multiple logistic regression analysis served to estimate the predictive effect of oral health literacy on self-reported oral health status (good versus poor) controlling for socioeconomic and demographic factors and tooth-brushing behavior. Results. In all, among 1031 partici...

  9. Refugee child oral health.

    Science.gov (United States)

    Riggs, E; Rajan, S; Casey, S; Kilpatrick, N

    2017-04-01

    The number of people forced to flee their homes and move around the world is increasing rapidly. Such refugee populations are not only more likely to have poor physical, mental and social health outcomes but also to experience difficulties accessing health services in their new country. In particular, children from refugee backgrounds are at increased risk of poor oral health which in time is associated with poor adult oral health and impacts on child health (e.g. growth and development) and well-being. To date, there is little evidence about the nature and extent of their oral health problems nor interventions to improve their oral health status. This article summarises the evidence surrounding the oral health status of children from refugee backgrounds. In addition, a systematic review of the international literature over the past 10 years is presented which identifies interventions to improve the oral health of these vulnerable paediatric populations. Based on this evidence, potential strategies available to dental service providers to optimise provision of responsive dental care are discussed. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Strengthening of oral health systems

    DEFF Research Database (Denmark)

    Petersen, Poul Erik

    2014-01-01

    Around the globe many people are suffering from oral pain and other problems of the mouth or teeth. This public health problem is growing rapidly in developing countries where oral health services are limited. Significant proportions of people are underserved; insufficient oral health care...... is either due to low availability and accessibility of oral health care or because oral health care is costly. In all countries, the poor and disadvantaged population groups are heavily affected by a high burden of oral disease compared to well-off people. Promotion of oral health and prevention of oral...... diseases must be provided through financially fair primary health care and public health intervention. Integrated approaches are the most cost-effective and realistic way to close the gap in oral health between rich and poor. The World Health Organization (WHO) Oral Health Programme will work...

  11. Graphite oral tattoo: case report

    OpenAIRE

    Moraes, Renata Mendonça; Gouvêa Lima, Gabriela de Morais; Guilhermino, Marinaldo; Vieira, Mayana Soares; Carvalho, Yasmin Rodarte; Anbinder, Ana Lia

    2015-01-01

    Pigmented oral lesions compose a large number of pathological entities, including exogenous pigmentat oral tattoos, such as amalgam and graphite tattoos. We report a rare case of a graphite tattoo on the palate of a 62-year-old patient with a history of pencil injury, compare it with amalgam tattoos, and determine the prevalence of oral tattoos in our Oral Pathology Service. We also compare the clinical and histological findings of grafite and amalgam tattoos. Oral tattoos affect women more f...

  12. Two monitoring methods of oral anticoagulant therapy in patients with mechanical heart valve prothesis: a meta-analysis.

    Science.gov (United States)

    Xu, Zhe; Wang, Zhiping; Ou, Jingsong; Xu, Yingqi; Yang, Song; Zhang, Xi

    2012-01-01

    Oral a