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  1. Genetically Guided Statin Therapy

    Science.gov (United States)

    2017-03-01

    number of new statin prescriptions, and (4) patient reported quality of life, physical activity, perceptions regarding statin therapy , and pain as...outcomes known to be prevented by statin therapy , we examined hospitalizations for three diagnoses: acute myocardial infarction (MI), stroke, and...cholesterol. However, the ultimate goal of statin therapy is to decrease incidence of CAD, acute myocardial infarction and perhaps stroke. However, there is a

  2. Viewpoint: Personalizing Statin Therapy

    Directory of Open Access Journals (Sweden)

    Shlomo Keidar

    2013-04-01

    Full Text Available Cardiovascular disease (CVD, associated with vascular atherosclerosis, is the major cause of death in Western societies. Current risk estimation tools, such as Framingham Risk Score (FRS, based on evaluation of multiple standard risk factors, are limited in assessment of individual risk. The majority (about 70% of the general population is classified as low FRS where the individual risk for CVD is often underestimated but, on the other hand, cholesterol lowering with statin is often excessively administered. Adverse effects of statin therapy, such as muscle pain, affect a large proportion of the treated patients and have a significant influence on their quality of life. Coronary artery calcification (CAC, as assessed by computed tomography, carotid artery intima-media thickness (CIMT, and especially presence of plaques as assessed by B-mode ultrasound are directly correlated with increased risk for cardiovascular events and provide accurate and relevant information for individual risk assessment. Absence of vascular pathology as assessed by these imaging methods has a very high negative predictive value and therefore could be used as a method to reduce significantly the number of subjects who, in our opinion, would not benefit from statins and only suffer from their side-effects. In summary, we suggest that in very-low-risk subjects, with the exception of subjects with low FRS with a family history of coronary artery disease (CAD at young age, if vascular imaging shows no CAC or normal CIMT without plaques, statin treatment need not be administered.

  3. Statin therapy for the octogenarian?

    African Journals Online (AJOL)

    2011-04-23

    Apr 23, 2011 ... placebo groups.41 A recent Cochrane meta-analysis identified three randomised trials of statin therapy in patients with established Alzheimer-type dementia. Statin therapy was not associated with improved cognition or functioning, although the results of one large randomised trial were still outstanding.42.

  4. Successful reintroduction of statin therapy after statin-associated rhabdomyolysis.

    Science.gov (United States)

    Simons, Janet E; Holbrook, Anne M; Don-Wauchope, Andrew C

    2015-01-01

    The case report demonstrates the successful use of an alternative statin after a statin-related episode of rhabdomyolysis. Statin-associated rhabdomyolysis is a serious adverse event with a very low incidence and is considered the most severe of the muscle-related side effects of the statins. Rechallenge with statins is not a recommended practice after rhabdomyolysis. The patient experienced a myocardial infarct 1 y after the episode of rhabdomyolysis. He used alternative lipid-lowering therapy for 2 y. His low-density lipoprotein cholesterol was not meeting typical secondary prevention targets. An alternative statin was introduced and the patient has been followed for 4 years without recurrence of the rhabdomyolysis. This case suggests it may be time to reconsider the accepted practice of permanently avoiding statin therapy after rhabdomyolysis. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  5. Statin Therapy: Review of Safety and Potential Side Effects.

    Science.gov (United States)

    Ramkumar, Satish; Raghunath, Ajay; Raghunath, Sudhakshini

    2016-11-01

    Hydroxymethyl glutaryl coenzyme A reductase inhibitors, commonly called statins, are some of the most commonly prescribed medications worldwide. Evidence suggests that statin therapy has significant mortality and morbidity benefit for both primary and secondary prevention from cardiovascular disease. Nonetheless, concern has been expressed regarding the adverse effects of long term statin use. The purpose of this article was to review the current medical literature regarding the safety of statins. Major trials and review articles on the safety of statins were identified in a search of the MEDLINE database from 1980 to 2016, which was limited to English articles. Myalgia is the most common side effect of statin use, with documented rates from 1-10%. Rhabdomyolysis is the most serious adverse effect from statin use, though it occurs quite rarely (less than 0.1%). The most common risk factors for statin-related myopathy include hypothyroidism, polypharmacy and alcohol abuse. Derangement in liver function tests is common, affecting up to 1% of patients; however, the clinical significance of this is unknown. Some statin drugs are potentially diabetogenic and the risk appears to increase in those patients on higher doses. Pitavastatin has not been associated with increased risk of diabetes. Statins have not been proven to increase the risk of malignancy, dementia, mood disorders or acute interstitial nephritis. However, statins do have multiple drug interactions, primarily those which interact with the cytochrome p450 enzyme group. Overall, statin drugs appear to be safe for use in the vast majority of patients. However, patients with multiple medical co-morbidities are at increased risk of adverse effects from long-term statin use.

  6. Comprehensive efforts to increase adherence to statin therapy

    DEFF Research Database (Denmark)

    Vonbank, Alexander; Agewall, Stefan; Kjeldsen, Keld Per

    2017-01-01

    There is compelling evidence that statin therapy improves cardiovascular morbidity and mortality. Unfortunately, statin adherence is far from optimal regarding initiation, execution and persistence of treatment over time.26 Poor adherence to statin therapy is associated with a significantly incre...

  7. Statins in primary biliary cirrhosis: are they safe?

    Science.gov (United States)

    Abu Rajab, Murad; Kaplan, Marshall M

    2010-07-01

    Although cholesterol levels are elevated in patients with primary biliary cirrhosis (PBC), most PBC patients are not at increased risk of dying from atherosclerotic heart disease. There is, however, a subgroup, approximately 10%, who have additional disorders of lipid metabolism. They might benefit from a cholesterol-lowering agent. However, there is concern about using statins in patients with pre-existing liver disease. We therefore reviewed our experience with statins in a large cohort of PBC patients who were seen at Tufts Medical Center during the past decade. From January 1, 1996, until June 30, 2006, 603 patients with PBC were seen by one of us (M.M.K.). Fifty-eight were on statins and five were on ezetimibe. The mean duration of usage was 41 months (range 3-125 months). Alanine aminotransferase (ALT) levels were measured at 3-month intervals. Statins were well tolerated. No patient complained of muscle pain or weakness. There was no increase in ALT levels. ALT levels were slightly elevated at the time that statins were begun (41.7 +/- 25.1 U/l), and were normal at the last time these patients were seen (39.0 +/- 21.0 U/l) (P Statins are safe in PBC patients who might benefit from their use.

  8. Statin-associated muscle symptoms: impact on statin therapy

    DEFF Research Database (Denmark)

    Stroes, Erik S; Thompson, Paul D; Corsini, Alberto

    2015-01-01

    degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal......Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin......-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms...

  9. Non-response to (statin) therapy

    DEFF Research Database (Denmark)

    Trompet, S; Postmus, I; Slagboom, P E

    2016-01-01

    PURPOSE: In pharmacogenetic research, genetic variation in non-responders and high responders is compared with the aim to identify the genetic loci responsible for this variation in response. However, an important question is whether the non-responders are truly biologically non-responsive......-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p levels (p ... that non-adherence is investigated instead of non-responsiveness....

  10. The case for statin therapy in chronic heart failure

    NARCIS (Netherlands)

    van der Harst, Pim; Boehm, Michael; van Gilst, Wiek H.; van Veldhuisen, Dirk J.

    Both primary and secondary prevention studies have provided a wealth of evidence that statin therapy effectively reduces cardiovascular events. However, this general statement on the efficacy and safety of statin treatment has not been validated in patients with chronic heart failure (CHF).

  11. Generic atorvastatin, the Belgian statin market and the cost-effectiveness of statin therapy.

    Science.gov (United States)

    Simoens, Steven; Sinnaeve, Peter R

    2013-02-01

    This study examines how the market entry of generic atorvastatin influences the Belgian statin market and the cost-effectiveness of statin therapy. Using IMS Health data, the Belgian 2000-2011 statin market was analyzed in terms of total expenditure, annual price of statin treatment, and patient numbers. A simulation analysis projected statin market shares from 2012 to 2015 following market entry of generic atorvastatin. This analysis was based on three scenarios regarding the number of patients taking specific statins. Savings associated with an atorvastatin price reduction of 50-70 % were calculated. A literature review of economic evaluations assessed the cost-effectiveness of generic atorvastatin. Statin expenditure increased from €113 million in 2000 to €285 million in 2011 due to higher expenditure on atorvastatin and rosuvastatin. Although the number of patients treated with simvastatin increased by nearly 800 %, the resulting increase in expenditure was partially offset by price reductions. Atorvastatin is projected to become the dominant product in the Belgian statin market (market share of 47-66 % by 2015). Annual savings would attain €108.6-€153.7 million for a 50 % reduction in the atorvastatin price and €152.0-€215.2 million for a 70 % price reduction. The literature suggests that generic atorvastatin is cost-effective as compared to simvastatin. The limited evidence about the cost-effectiveness of rosuvastatin as compared with generic atorvastatin is inconclusive. Generic atorvastatin is cost-effective as compared to simvastatin, is projected to become the dominant product in the Belgian statin market and is expected to generate substantial savings to health care payers.

  12. Statins Decrease Oxidative Stress and ICD Therapies

    Directory of Open Access Journals (Sweden)

    Heather L. Bloom

    2010-01-01

    Full Text Available Recent studies demonstrate that statins decrease ventricular arrhythmias in internal cardioverter defibrillator (ICD patients. The mechanism is unknown, but evidence links increased inflammatory and oxidative states with increased arrhythmias. We hypothesized that statin use decreases oxidation. Methods. 304 subjects with ICDs were surveyed for ventricular arrhythmia. Blood was analyzed for derivatives of reactive oxygen species (DROMs and interleukin-6 (IL-6. Results. Subjects included 252 (83% men, 58% on statins, 20% had ventricular arrhythmias. Average age was 63 years and ejection fraction (EF 20%. ICD implant duration was 29 ± 27 months. Use of statins correlated with lower ICD events (r=0.12, P=.02. Subjects on statins had lower hsCRP (5.2 versus 6.3; P=.05 and DROM levels (373 versus 397; P=.03. Other factors, including IL-6 and EF did not differ between statin and nonstatin use, nor did beta-blocker or antiarrhythmic use. Multivariate cross-correlation analysis demonstrated that DROMs, statins, IL-6 and EF were strongly associated with ICD events. Multivariate regression shows DROMs to be the dominant predictor. Conclusion. ICD event rate correlates with DROMs, a measure of lipid peroxides. Use of statins is associated with reduced DROMs and fewer ICD events, suggesting that statins exert their effect through reducing oxidation.

  13. Continuation of Statin Therapy and Vasopressor Use in Septic Shock.

    Science.gov (United States)

    Zechmeister, Carrie; Hurren, Jeff; McNorton, Kelly

    2015-07-01

    Studies have evaluated the use of statins in sepsis; however, no human studies have explored their effect on vasopressor requirements in septic shock. The primary objective was to determine the effect of prehospital statin continuation on duration of vasopressor therapy in patients with septic shock. Secondary objectives included maximum and average vasopressor dose and in-hospital mortality. This was a retrospective, institutional board-approved, observational cohort study in a community teaching hospital; 119 adult intensive care unit (ICU) patients with an ICD-9 code for septic shock and prehospital statin therapy were evaluated. Multivariate analyses were performed to address confounders. Of the 1229 patients screened, 119 (10%) met inclusion criteria; 73 patients (61%) had a statin continued within 24 hours of ICU admission. Crude analysis demonstrated no difference in vasopressor duration in the statin versus no statin group (3.3 vs 4.8 days; P = 0.21). There was no difference in either maximum (17.9 ± 16.1 vs 23.8 ± 21.7 µg/min norepinephrine equivalents [NEQs]; P = 0.1) or average vasopressor dose (9.5 ± 8.4 vs 12.1 ± 11.5 µg/min NEQ; P = 0.17). There was a decrease in mortality in the statin patients (43% vs 67 %; P = 0.05). On adjustment for potential confounders, there was no difference in any outcome, with a persistent trend toward lower mortality in the statin group. Continuation of prehospital statin therapy decreased neither duration nor dose of vasopressors in patients with septic shock but yielded a trend toward decreased mortality. © The Author(s) 2015.

  14. Somatic symptoms of anxiety and nonadherence to statin therapy.

    Science.gov (United States)

    Korhonen, Maarit Jaana; Pentti, Jaana; Hartikainen, Juha; Kivimäki, Mika; Vahtera, Jussi

    2016-07-01

    The association between anxiety and nonadherence to preventive therapies remains unclear. We investigated whether somatic symptoms of anxiety predict statin nonadherence. This is a prospective cohort study of 1924 individuals who responded to a questionnaire survey on health status and initiated statin therapy after the survey during 2008-2010. We followed the cohort for nonadherence, defined as the proportion of days covered pain upon anger or emotion, sweating without exercise, flushing, tremor of hands or voice, muscle twitching) before the statin initiation, and 16% had experienced at least one symptom on average weekly to daily. 49% of respondents were nonadherent. Weekly to daily occurrence of these symptoms predicted a 33% increase in the risk of nonadherence (risk ratio [RR] 1.33, 95% confidence interval, CI, 1.13-1.57) compared to no symptoms when adjusted for sociodemographics, lifestyle risks, cardiovascular comorbidities, and depression. Particularly, chest pain upon anger or emotion (RR 1.21, 95% CI 1.01-1.46) and muscle twitching (RR 1.24, 95% CI 1.08-1.42) predicted an increased risk of nonadherence to statin therapy. Psychological symptoms of anxiety were not associated with nonadherence when adjusted for somatic symptoms. Somatic anxiety-related symptoms predicted nonadherence to statin therapy. Information on pre-existing somatic symptoms may help identifying patients at increased risk of statin nonadherence. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Genetically Guided Statin Therapy on Statin Perceptions, Adherence, and Cholesterol Lowering: A Pilot Implementation Study in Primary Care Patients

    Directory of Open Access Journals (Sweden)

    Josephine H. Li

    2014-03-01

    Full Text Available Statin adherence is often limited by side effects. The SLCO1B1*5 variant is a risk factor for statin side effects and exhibits statin-specific effects: highest with simvastatin/atorvastatin and lowest with pravastatin/rosuvastatin. The effects of SLCO1B1*5 genotype guided statin therapy (GGST are unknown. Primary care patients (n = 58 who were nonadherent to statins and their providers received SLCO1B1*5 genotyping and guided recommendations via the electronic medical record (EMR. The primary outcome was the change in Beliefs about Medications Questionnaire, which measured patients’ perceived needs for statins and concerns about adverse effects, measured before and after SLCO1B1*5 results. Concurrent controls (n = 59 were identified through the EMR to compare secondary outcomes: new statin prescriptions, statin utilization, and change in LDL-cholesterol (LDL-c. GGST patients had trends (p = 0.2 towards improved statin necessity and concerns. The largest changes were the “need for statin to prevent sickness” (p < 0.001 and “concern for statin to disrupt life” (p = 0.006. GGST patients had more statin prescriptions (p < 0.001, higher statin use (p < 0.001, and greater decrease in LDL-c (p = 0.059 during follow-up. EMR delivery of SLCO1B1*5 results and recommendations is feasible in the primary care setting. This novel intervention may improve patients’ perceptions of statins and physician behaviors that promote higher statin adherence and lower LDL-c.

  16. Relation of statin therapy to psychological functioning in patients with an implantable cardioverter defibrillator

    DEFF Research Database (Denmark)

    Hoogwegt, Madelein T; Theuns, Dominic A M J; Kupper, Nina

    2013-01-01

    Statin therapy is an important secondary prevention measure in cardiovascular disease. However, the side effects associated with statin use could potentially affect patients' quality of life. Little is known about the influence of statin therapy on the well-being and health status of cardiac...... patients, in general, and patients with an implantable cardioverter defibrillator (ICD), in particular. We investigated the association between statin therapy and symptoms of anxiety and depression and patients' health status during the 12 months after implantation, reckoning with statin type and dosage...... of statin type, dosage, and other potential confounders. The associations between statin therapy and depression (p = 0.06) and statin therapy and physical functioning (p = 0.05) were borderline significant, and no association was found with anxiety (p >0.05). In conclusion, statin therapy was associated...

  17. Statins and protein prenylation in cancer cell biology and therapy.

    Science.gov (United States)

    Garcia-Ruiz, Carmen; Morales, Albert; Fernandez-Checa, Jose C

    2012-05-01

    The use of statins has scaled up to become one of the most prescribed medicines in the world and have been very useful in the manegement of cardiovascular diseases and related mortality. The disclosure of their chemical structure similar to that of hydroxy methyl glutaryl-CoA (HMG-CoA) revealed their ability to compete with and inhibit the rate-limiting enzyme HMG-CoA reductase that catalyzes the synthesis of mevalonate, which then serves as the precursor for isoprenoids and cholesterol in the mevalonate pathway. While most of the effects of statins are associated with the lowering of cellular cholesterol levels, it is clear that they also blunt the non-sterol branch of the mevalonate pathway, decreasing formation of isoprenoids and altering protein-prenylation, a critical event in the posttranslational modulation of proteins involved in the regulation of cell cycle progression, proliferation and signaling pathways. Randomized controlled trials for the prevention of cardiovascular diseases indicated that statins elicited provocative and unexpected benefits for reducing a number of different types of cancers, including colorectal carcinoma, melanoma, prostate and hepatocellular carcinoma, although in other cancer types the preclinical expectations of statins were dissapointing. In this review, we will describe the evidence and mechanisms underlying the potential beneficial use of statins and the role of protein prenylation in cancer prevention. Of relevance, the combination of statins with other anti cancer drugs may be a significant asset in malignancies resistant to current therapy.

  18. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes

    NARCIS (Netherlands)

    Cannon, Christopher P.; Blazing, Michael A.; Giugliano, Robert P.; McCagg, Amy; White, Jennifer A.; Theroux, Pierre; Darius, Harald; Lewis, Basil S.; Oude Ophuis, Ton; Jukema, J. Wouter; de Ferrari, Gaetano M.; Ruzyllo, Witold; de Lucca, Paul; Im, KyungAh; Bohula, Erin A.; Reist, Craig; Wiviott, Stephen D.; Tershakovec, Andrew M.; Musliner, Thomas A.; Braunwald, Eugene; Califf, Robert M.; Musliner, Thomas; Tershakovec, Andrew; Gurfinkel, Enrique; Aylward, Philip; Tonkin, Andrew; Maurer, Gerald; van de Werf, Frans; Nicolau, Jose C.; Genest, Jacques; Armstrong, Paul; Corbalan, Ramon; Isaza, Daniel; Spinar, Jindrich; Grande, Peer; Voitk, Juri; Kesaniemi, Antero; Bassand, Jean-Pierre; Farnier, Michel; Keltai, Matyas; Mathur, Atul; Mittal, Sanjay; Reddy, Krishna; Lewis, Basil; White, Harvey; Pedersen, Terje; Britto, Frank; Carrageta, Manuel; Duris, Tibor; Nijmeijer, R.

    2015-01-01

    BACKGROUND Statin therapy reduces low-density lipoprotein (LDL) cholesterol levels and the risk of cardiovascular events, but whether the addition of ezetimibe, a nonstatin drug that reduces intestinal cholesterol absorption, can reduce the rate of cardiovascular events further is not known. METHODS

  19. Relation of statin therapy to psychological functioning in patients with an implantable cardioverter defibrillator

    NARCIS (Netherlands)

    Hoogwegt, M.T.; Theuns, D.A.M.J.; Kupper, N.; Jordaens, L.; Pedersen, S.S.

    2013-01-01

    Statin therapy is an important secondary prevention measure in cardiovascular disease. However, the side effects associated with statin use could potentially affect patients' quality of life. Little is known about the influence of statin therapy on the well-being and health status of cardiac

  20. Underutilization of high-intensity statin therapy after hospitalization for coronary heart disease.

    Science.gov (United States)

    Rosenson, Robert S; Kent, Shia T; Brown, Todd M; Farkouh, Michael E; Levitan, Emily B; Yun, Huifeng; Sharma, Pradeep; Safford, Monika M; Kilgore, Meredith; Muntner, Paul; Bittner, Vera

    2015-01-27

    National guidelines recommend use of high-intensity statins after hospitalization for coronary heart disease (CHD) events. This study sought to estimate the proportion of Medicare beneficiaries filling prescriptions for high-intensity statins after hospital discharge for a CHD event and to analyze whether statin intensity before hospitalization is associated with statin intensity after discharge. We conducted a retrospective cohort study using a 5% random sample of Medicare beneficiaries between 65 and 74 years old. Beneficiaries were included in the analysis if they filled a statin prescription after a CHD event (myocardial infarction or coronary revascularization) in 2007, 2008, or 2009. High-intensity statins included atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg, and simvastatin 80 mg. Among 8,762 Medicare beneficiaries filling a statin prescription after a CHD event, 27% of first post-discharge fills were for a high-intensity statin. The percent filling a high-intensity statin post-discharge was 23.1%, 9.4%, and 80.7%, for beneficiaries not taking statins pre-hospitalization, taking low/moderate-intensity statins, and taking high-intensity statins before their CHD event, respectively. Compared with beneficiaries not on statin therapy pre-hospitalization, multivariable adjusted risk ratios for filling a high-intensity statin were 4.01 (3.58-4.49) and 0.45 (0.40-0.52) for participants taking high-intensity and low/moderate-intensity statins before their CHD event, respectively. Only 11.5% of beneficiaries whose first post-discharge statin fill was for a low/moderate-intensity statin filled a high-intensity statin within 365 days of discharge. The majority of Medicare beneficiaries do not fill high-intensity statins after hospitalization for CHD. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  1. Combined statin-fibrate therapy-induced rhabdomyolysis: Case report

    Directory of Open Access Journals (Sweden)

    Jozić Tanja L.

    2014-01-01

    Full Text Available Introduction Rhabdomyolysis is a rare, but serious and potentially fatal adverse reaction of the statin application that may be developed in any time of therapy. It is characterized by massive destruction of muscles associated with the large increase of creatine kinase (CK leading to myoglobinuria and potential acute renal failure. Combined statin-fibrate therapy increases the risk of rhabdomyolysis, especially in elderly and diabetic patients. Case report An 81-year-old male was admitted to Coronary Care Unit of the Emergency Center, Clinical Center of Serbia (CCS with the clinical picture and electrocardiogram of the acute anterior wall myocardial infarction complicated with pulmonary edema. Laboratory tests on admission showed higher elevated values of serum creatinine 179 μmol/L and BUN 9.2 mmol/L (eGFR 32 mL/min/1.73m2, CK 309 U/L (on day 2: 3476 U/L and mixed hyperlipidemia (total cholesterol 10.3 mmol/L, HDL 2.26 mmol/L, TG 4.85 mmol/L. The patient was treated with thrombolysis medication therapy (Alteplase, anticoagulant and dual antiplatelet therapy, diuretics, organic nitrates, angiotensin-converting enzyme (ACE inhibitors, antibiotics, and proton pump inhibitors. During seven days, his therapy included combined pravastatin 20 mg and fenofibrate (160 mg, which was discontinued due to pains and weakness of muscles and significantly elevated CC to 7080 U/L (upper limit 200 U/L, but no significant deterioration of renal function was observed. Discontinuation of therapy resulted in CC level normalization and improvement of clinical condition. Conclusion Combined statin and fibrate therapy requires strict clinical control and monitoring of CK i transaminases. Four-time or higher increase of CK requires discontinuation of therapy. In addition, patients are advised to report immediately any pains in muscles, sensibility, weakness or cramps.

  2. Neuromuscular Effects of Rocuronium Bromide in Patients in Statin Therapy for at least Three Months.

    Science.gov (United States)

    Ren, Hongwei; Lv, Huangwei

    2016-12-01

    Statins cause skeletal muscle myopathy. However, the neuromuscular effects of non-depolarizing neuromuscular-blocking agent in patients in long-term statin therapy remain unclear. Hence, we investigated the neuromuscular effects of rocuronium and muscle injury in patients in long-term statin therapy. Eighteen statin users using statins for at least 3 months were included in the statin group and 18 non-statin users were included in the non-statin group. General anaesthesia was induced with intravenous midazolam, etomidate, sufentanil and rocuronium 0.9 mg/kg (3ED 95 ) for intubation. Anaesthesia was maintained with 1% propofol and remifentanil. The onset time and duration 10% T 1 and 25% T 1 of rocuronium were recorded. Blood samples were obtained before induction and 5 min., 1 hr, 2 hr, 4 hr, 12 hr and 24 hr after rocuronium administration to measure creatine kinase (CK), myoglobin and potassium. Myalgia was determined at 2 and 24 hr after surgery. There were no significant differences in the basic clinical characteristics between the two groups. The onset time of the statin group was significantly shorter than that of the non-statin group (p = 0.02), while the duration 10% T 1 and duration 25% T 1 of the statin group were significantly longer than those of the non-statin group (p = 0.006; p = 0.045). The myoglobin and CK concentrations increased after rocuronium administration as compared to baseline in both groups. CK concentration in the statin group was significantly higher than in the non-statin group just at 24 hr (p = 0.000003). However, myoglobin showed no significant difference between the two groups. The onset time of rocuronium decreases and its duration time increases in patients in long-term statin therapy. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  3. Efficacy and safety of statins and exercise combination therapy compared to statin monotherapy in patients with dyslipidaemia: A systematic review and meta-analysis.

    Science.gov (United States)

    Gui, Ya-Jun; Liao, Cai-Xiu; Liu, Qiong; Guo, Yuan; Yang, Tao; Chen, Jing-Yuan; Wang, Ya-Ting; Hu, Jia-Hui; Xu, Dan-Yan

    2017-06-01

    Background Statin treatment in association with physical exercise can substantially reduce mortality in dyslipidaemic individuals. However, the available data to compare the efficacy and safety of statins and exercise combination therapy with statin monotherapy are limited. Design Systematic review and meta-analysis. Methods We systematically searched PubMed, Embase and the Cochrane Library from database inception until December 2016. We included randomised and non-randomised studies that compared the efficacy and safety of statins and exercise combination therapy with statin monotherapy in patients with dyslipidaemia. Standardised mean differences were calculated and pooled by means of fixed effects models. The risk of bias and heterogeneity among trials was also assessed. Seven articles were assessed in terms of the efficacy of therapy and 13 from the viewpoint of therapeutic safety. Results In terms of efficacy, statins and exercise combination decreased the incidence of diabetes mellitus, improved insulin sensitivity and inflammation, but caused no change in lipid profile compared to statins alone. In terms of safety, statins and exercise combination increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced myopathy, chronic exercise training prior to statin treatment could counteract statin-induced adverse effects in skeletal muscle. Conclusion Statins and exercise combination therapy is more effective than statin monotherapy in terms of insulin sensitivity, inflammation and exercise capacity. The small number of studies warrants the need for more randomised controlled trials evaluating the efficacy and safety of combination therapy.

  4. NEW POSSIBILITIES OF STATIN THERAPY IN ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    E. M. Khurs

    2010-01-01

    Full Text Available Background. Effects of statins on cardiovascular end points are well-known. To study the impact of statins on structural and functional heart remodeling in patients with arterial hypertension (HT seemsto be topical.Aim. To study the effect of statins on cardiac remodeling in patients with HT.Materials and methods. 120 patients with HT of 1 degree were included into the study: 56 men, 64 women, aged 52.4±10.23. Patients were randomized into 4 treatment groups: Group A1 (angiotensin converting enzyme (ACE inhibitors + diet, group A2 (ACE inhibitor + fluvastatin, group B1 (angiotensin II receptor antagonist (ARA II + diet, group B2 (ARAII + fluvastatin. Transthoracic echocardiography with calculation of standard left ventricle (LV remodeling indices was performed.Results. The most important prognostic markers of LV remodeling were revealed. They were a basis for definition of 3 types of early LV remodeling: type 1 — compensated, type 2 — adaptive, 3 type — maladaptive. After 6 months of treatment a number of patients in group A1 with type 2 and type 3 of LV remodeling reduced less (2%, p=0.02 and 4%, p=0.04, respectively than this in group A2 (14%, p=0.04 and 4%, p=0.04, respectively. A number of patients with type 1 (compensated of LV remodeling increased by 18% (p<0.001 in group A2, and by 6%, (p=0.03 in group A1. After the treatment a number of patients with type 3 and type 2 of LV remodeling decreased (p<0.001 and p=0.04, respectively in groups B1 and B2 while a number of patients with type 1 of LV remodeling increased (p<0,001. A number of patients with type 1 of LV remodeling increased and this with type 3 of LV remodeling decreased in group B2 more prominently in comparison with group A2 (p=0.03; p=0.01, respectively.Conclusion. Statins in patients with HT have cardioprotective effect that does not depend on basic antihypertensive therapy and total cholesterol level. In these patients combination of statins with ARA II has better

  5. Statin therapy and the risk for diabetes among adult women: do the benefits outweigh the risk?

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    Ma, Yunsheng; Culver, Annie; Rossouw, Jacques; Olendzki, Barbara; Merriam, Philip; Lian, Bill; Ockene, Ira

    2013-02-01

    The purpose of this review was to examine statin therapy and the risk for diabetes among adult women using a selective review. The literature contains reports of new-onset diabetes associated with statin use. While many studies do not report sex-specific results, there is evidence indicating the risk to benefit ratio may vary by gender. However, the absolute effects are not clear because women have historically been under-represented in clinical trials. A review of the literature indicates that the cardiovascular benefits of statins appear to outweigh the risk for statin-related diabetes. However, the effect may depend upon baseline diabetes risk, dose, and statin potency. Rigorous, long-term studies focused on the risks and benefits of statins in women are unavailable to sort for gender-specific differences. Until this changes, individualized attention to risk assessment, and strong prevention with lifestyle changes must prevail.

  6. A Pharmaceutical Care Program to Improve Adherence to Statin Therapy : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Eussen, Simone R. B. M.; van der Elst, Menno E.; Klungel, Olaf H.; Rompelberg, Cathy J. M.; Garssen, Johan; Oosterveld, Marco H.; de Boer, Anthonius; de Gier, Johan J.; Bouvy, Marcel L.

    2010-01-01

    BACKGROUND: Despite the well-known beneficial effects of statins, many patients do not adhere to chronic medication regimens. OBJECTIVE: To implement and assess the effectiveness of a community pharmacy based pharmaceutical care program developed to improve patients' adherence to statin therapy.

  7. Association between acute statin therapy, survival, and improved functional outcome after ischemic stroke: the North Dublin Population Stroke Study.

    LENUS (Irish Health Repository)

    2011-04-01

    Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study.

  8. Gonadal steroids, gonadotropins and DHEAS in young adults with familial hypercholesterolemia who had initiated statin therapy in childhood

    NARCIS (Netherlands)

    Braamskamp, Marjet J. A. M.; Kusters, D. Meeike; Wiegman, Albert; Avis, Hans J.; Wijburg, Frits A.; Kastelein, John J. P.; van Trotsenburg, A. S. Paul; Hutten, Barbara A.

    2015-01-01

    Statins are currently the preferred pharmacological therapy in children with familial hypercholesterolemia (FH) with the aim to prevent premature cardiovascular disease (CVD). However, concerns have been raised that lowering cholesterol levels with statins could interfere with hormone production. In

  9. APPLIED ASPECTS OF SLCO1B1 PHARMACOGENETIC TESTING FOR PREDICTING OF STATIN-INDUCED MYOPATHY AND PERSONALIZATION OF STATINS THERAPY

    Directory of Open Access Journals (Sweden)

    D. A. Sychev

    2015-09-01

    Full Text Available The clinical significance of the SLCO1B1 gene polymorphism (encoding an organic anion transport polipeptide in the development of statin induced myopathy is considered. Possible tactics of statin dose determination on the basis of pharmacogenetic testing is discussed. Indications for the use of this approach in clinical practice that should increase the efficacy and safety of the statin therapy are also considered.

  10. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management.

    Science.gov (United States)

    Stroes, Erik S; Thompson, Paul D; Corsini, Alberto; Vladutiu, Georgirene D; Raal, Frederick J; Ray, Kausik K; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G; Bruckert, Eric; De Backer, Guy; Krauss, Ronald M; Laufs, Ulrich; Santos, Raul D; Hegele, Robert A; Hovingh, G Kees; Leiter, Lawrence A; Mach, Francois; März, Winfried; Newman, Connie B; Wiklund, Olov; Jacobson, Terry A; Catapano, Alberico L; Chapman, M John; Ginsberg, Henry N

    2015-05-01

    Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7-29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology.

  11. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, Thomas P; Lash, Timothy L; Damkier, Per

    2014-01-01

    Much preclinical and epidemiological evidence supports the anticancer effects of statins. Epidemiological evidence does not suggest an association between statin use and reduced incidence of breast cancer, but does support a protective effect of statins-especially simvastatin-on breast cancer...... recurrence. Here, we argue that the existing evidence base is sufficient to justify a clinical trial of breast cancer adjuvant therapy with statins and we advocate for such a trial to be initiated without delay. If a protective effect of statins on breast cancer recurrence is supported by trial evidence......, then the indications for a safe, well tolerated, and inexpensive treatment can be expanded to improve outcomes for breast cancer survivors. We discuss several trial design opportunities-including candidate predictive biomarkers of statin safety and efficacy-and off er solutions to the key challenges involved...

  12. Statin Therapy as Primary Prevention in Exercising Adults: Best Evidence for Avoiding Myalgia.

    Science.gov (United States)

    Bosomworth, N John

    This review aims to determine whether active adults who begin statins and develop myalgia reduce or stop activity to become less symptomatic. If this occurs, strategies to mitigate symptoms are explored. Should these strategies fail, the question of whether exercise is an adequate alternative to statin therapy is addressed. PubMed, Google Scholar, and the Cochrane Database were searched with keywords designed to retrieve information on statin myopathy in exercising adults. Statins are well tolerated by most people who exercise; however, caution is warranted in those who exercise at high levels, in the elderly, and in those receiving high-dose therapy. Several strategies improve statin tolerance while maintaining exercise levels, based on low-quality evidence. If statins are not tolerated, a continuing physical activity program can provide equivalent or superior cardiometabolic protection. Statins may occasionally present a barrier to physical activity. A number of strategies exist that can reduce the risk of myopathy. If a choice between exercise and statins becomes necessary, exercise provides equal benefit in terms of cardiovascular protection and superior mortality reduction, with improved quality of life. © Copyright 2016 by the American Board of Family Medicine.

  13. Patients' perspectives on statin therapy for treatment of hypercholesterolaemia: a qualitative study.

    Science.gov (United States)

    Tolmie, Elizabeth P; Lindsay, Grace M; Kerr, Susan M; Brown, Malcom R; Ford, Ian; Gaw, Allan

    2003-07-01

    Health Care Practitioners' attempts to implement secondary prevention targets for coronary heart disease (CHD) may be restricted by low rates of persistence with statin therapy. There is a need to understand why some patients, despite having established CHD and elevated cholesterol, do not comply with their prescribed statin regimen. To explore patients' perspectives on compliance with statin therapy. Primary care, West of Scotland. The research approach was qualitative. Thirty-three patients prescribed statin therapy and identified as having different patterns of compliance (poor moderate and good) were interviewed. The in-depth interviews were conducted on a one to one basis. Patients prescribed statin therapy for less than three months were excluded. Data were analysed thematically with the assistance of QSR Nudist. From analysis of the narrative data, two broad categories, i.e. 'Patient-health care provider communication' and 'Health beliefs' were identified. These categories encompassed six main themes: 'Initiation of therapy'; 'Subsequent feedback'; 'Sources of misconceptions'; 'Unconditional acceptance'; 'Conditional acceptance'; 'Deferment and Rejection'. Acceptance of and compliance with statin therapy appeared to be associated with the provision, interpretation and feedback of information during patient-practitioner consultations, and patients' beliefs about personal health status, cholesterol, and recommended cholesterol-lowering strategies. Patients' beliefs and understanding about cholesterol, and the role of cholesterol modifying strategies should be determined prior to the initiation of therapy and at appropriate intervals thereafter.

  14. Benefits of statin therapy and compliance in high risk cardiovascular patients

    Directory of Open Access Journals (Sweden)

    Joel A Lardizabal

    2010-09-01

    Full Text Available Joel A Lardizabal1, Prakash C Deedwania21Division of Cardiology, Department of Medicine, University of California in San Francisco (Fresno-MEP, Fresno, CA, USA; 2University of California in San Francisco, Chief of Cardiology, Veterans Affairs Central California System, Fresno, CA, USAAbstract: Cardiovascular disease (CVD remains the top cause of global mortality. There is considerable evidence that supports the mortality and morbidity benefit of statin therapy in coronary heart disease (CHD and stroke, both in primary and secondary prevention settings. Data also exist pointing to the advantage of statin treatment in other high-risk CVD conditions, such as diabetes, CKD, CHF, and PVD. National and international clinical guidelines in the management of these CVD conditions all advocate for the utilization of statin therapy in appropriate patients. However, overall compliance to statin therapy remains suboptimal. Patient-, physician-, and economic-related factors all play a role. These factors need to be considered in devising approaches to enhance adherence to guideline-based therapies. To fully reap the benefits of statin therapy, interventions which improve long-term treatment compliance in real-world settings should be encouraged.Keywords: cardiovascular disease, statin therapy, coronary heart disease, long-term treatment compliance

  15. Statin therapy in lower limb peripheral arterial disease: Systematic review and meta-analysis.

    Science.gov (United States)

    Antoniou, George A; Fisher, Robert K; Georgiadis, George S; Antoniou, Stavros A; Torella, Francesco

    2014-11-01

    To investigate and analyse the existing evidence supporting statin therapy in patients with lower limb atherosclerotic arterial disease. A systematic search of electronic information sources was undertaken to identify studies comparing cardiovascular outcomes in patients with lower limb peripheral arterial disease treated with a statin and those not receiving a statin. Estimates were combined applying fixed- or random-effects models. Twelve observational cohort studies and two randomised trials reporting 19,368 patients were selected. Statin therapy was associated with reduced all-cause mortality (odds ratio 0.60, 95% confidence interval 0.46-0.78) and incidence of stroke (odds ratio 0.77, 95% confidence interval 0.67-0.89). A trend towards improved cardiovascular mortality (odds ratio 0.62, 95% confidence interval 0.35-1.11), myocardial infarction (odds ratio 0.62, 95% confidence interval 0.38-1.01), and the composite of death/myocardial infarction/stroke (odds ratio 0.91, 95% confidence interval 0.81-1.03), was identified. Meta-analyses of studies performing adjustments showed decreased all-cause mortality in statin users (hazard ratio 0.77, 95% confidence interval 0.68-0.86). Evidence supporting statins' protective role in patients with lower limb peripheral arterial disease is insufficient. Statin therapy seems to be effective in reducing all-cause mortality and the incidence cerebrovascular events in patients diagnosed with peripheral arterial disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Statin therapy and mortality in HIV-infected individuals; a Danish nationwide population-based cohort study

    DEFF Research Database (Denmark)

    Rasmussen, Line; Kronborg, Gitte; Larsen, Carsten S

    2013-01-01

    Recent studies have suggested that statins possess diverse immune modulatory and anti-inflammatory properties. As statins might attenuate inflammation, statin therapy has been hypothesized to reduce mortality in HIV-infected individuals. We therefore used a Danish nationwide cohort of HIV......-infected individuals to estimate the impact of statin use on mortality before and after a diagnosis of cardiovascular disease, chronic kidney disease or diabetes....

  17. High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease.

    Science.gov (United States)

    Foley, T Raymond; Singh, Gagan D; Kokkinidis, Damianos G; Choy, Ho-Hin K; Pham, Thai; Amsterdam, Ezra A; Rutledge, John C; Waldo, Stephen W; Armstrong, Ehrin J; Laird, John R

    2017-07-15

    The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P =0.14). Demographics including age (68±12 versus 67±10 years, P =0.25), smoking history (76% versus 80%, P =0.42), diabetes mellitus (54% versus 48%, P =0.17), and hypertension (88% versus 89%, P =0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P =0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P =0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P =0.02). In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  18. Adherence to statin therapy in patients with type 2 diabetes: An important dilemma

    Directory of Open Access Journals (Sweden)

    Shadi Farsaei

    2015-01-01

    Full Text Available Background: Despite the importance of patients′ adherence to their drug treatments for achieving desired therapeutic goals and the proven role 3-hydroxy-3-methylglutaryl coenzyme A inhibitors (statins for the health status of patients with cardiovascular diseases, there is not enough information regarding diabetic patients′ adherence to statin therapy in developing countries. In this clinical study we aimed to assess the adherence of diabetes type 2 patients to statin therapy in a research based community clinic in Iran. Materials and Methods: In this prospective clinical study which was done at Isfahan Endocrinology and Metabolism Research Center, 204 diabetic type 2 patients under treatment with statin were interviewed twice and their demographic data (age, gender, body mass index, education, statin information (type, dose and their serum lipid profile were recorded. Three months after the initial visits, patients were assessed using pill counting method and according to patients′ self-reporting and also assessed low-density lipoprotein (LDL cholesterol goal attainment <100 mg/dl. Results: Adherence rate was 79.7% and 69% according to pill counting and self-reporting among study population. Moreover, 68.4% of patients achieved their LDL cholesterol goal of <100 mg/dl and adherent patients reached therapeutic goal significantly more than those who were considered non-adherence to statin therapy (P < 0.01. Conclusion: Adherence to statin therapy, as reflected by pill count method, is significantly related to LDL cholesterol goal achievement in patients with diabetes and dyslipidemia. Pill count method can be used to identify patients who are nonadherent to statin therapy and at high risk for failure to attain LDL cholesterol goals.

  19. Correlation of compliance to statin therapy with lipid profile and serum HMGCoA reductase levels in dyslipidemic patients.

    Science.gov (United States)

    Grover, Abhinav; Rehan, Harmeet Singh; Gupta, Lalit Kumar; Yadav, Madhur

    The efficacy of statin therapy may be lost or vary with reduction in compliance and intensity of statin therapy. To study and correlate the quantitative effect of compliance on lipid profile and 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMGCoA-R) levels in dyslipidemic patients. Compliance to different intensity of statin therapy assessed by pill count was correlated with serum levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (TG), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB) and HMGCoA-R. Out of 200 patients, 160 received moderate intensity statin therapy whereas 40 were on high intensity statin therapy. The overall mean compliance of patients was 56.7%. The compliance of patients on moderate intensity statin therapy was higher (56.8%) than those on high intensity (56.4%) (p=0.92). There was significant inverse correlation (pstatin therapy was increased above 60%. It is appropriate to improve the compliance to existing statin therapy than switching over to higher intensity statin therapy. Estimation of HMGCoA-R levels may be explored as a surrogate marker to monitor and assess the compliance of patients to statin therapy. Copyright © 2016. Published by Elsevier B.V.

  20. Efficacy and safety of statin and fibrate combination therapy in lipid management.

    Science.gov (United States)

    Kota, Sunil Kumar; Meher, Lalit Kumar; Rao, Epari Sanjeeva; Jammula, Sruti; Modi, Kirtikumar D

    2012-01-01

    Adequate control of hyperlipidemia is of paramount importance for prevention of vascular events. Statins and fibrates are well established treatments for hyperlipidemia. Combination therapy with a statin and fibrate offers significant therapeutic advantage for the treatment of severe or refractory mixed hyperlipidemia. Although such a combination does increase the risk of myopathy, with an incidence of approximately 0.12%, this small risk of myopathy rarely outweighs the established morbidity and mortality benefits of achieving lipid goals. Nevertheless, a higher incidence of myopathy has been reported with statin monotherapy. Statin+fibrate therapy should be considered if monotherapy or adding other drugs (e.g. cholesterol absorption inhibitors, omega-3 fatty acids or nicotinic acid) did not achieve lipid targets or is impractical. The current article focuses on recent studies highlighting the beneficial effects of this combination. Copyright © 2012 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  1. Statin dose reduction with complementary diet therapy: A pilot study of personalized medicine

    Directory of Open Access Journals (Sweden)

    Bianca Scolaro

    2018-05-01

    Full Text Available Objective: Statin intolerance, whether real or perceived, is a growing issue in clinical practice. Our aim was to evaluate the effects of reduced-dose statin therapy complemented with nutraceuticals. Methods: First phase: Initially, 53 type 2 diabetic statin-treated patients received a supplementation with fish oil (1.7 g EPA + DHA/day, chocolate containing plant sterols (2.2 g/day, and green tea (two sachets/day for 6 weeks. Second phase: “Good responders” to supplementation were identified after multivariate analysis (n = 10, and recruited for a pilot protocol of statin dose reduction. “Good responders” were then provided with supplementation for 12 weeks: standard statin therapy was kept during the first 6 weeks and reduced by 50% from weeks 6–12. Results: First phase: After 6 weeks of supplementation, plasma LDL-C (−13.7% ± 3.7, P = .002 and C-reactive protein (−35.5% ± 5.9, P = .03 were reduced. Analysis of lathosterol and campesterol in plasma suggested that intensity of LDL-C reduction was influenced by cholesterol absorption rate rather than its synthesis. Second phase: no difference was observed for plasma lipids, inflammation, cholesterol efflux capacity, or HDL particles after statin dose reduction when compared to standard therapy. Conclusions: Although limited by the small sample size, our study demonstrates the potential for a new therapeutic approach combining lower statin dose and specific dietary compounds. Further studies should elucidate “good responders” profile as a tool for personalized medicine. This may be particularly helpful in the many patients with or at risk for CVD who cannot tolerate high dose statin therapy. Trial registration: ClinicalTrials.gov, NCT02732223. Keywords: Atherosclerosis, Omega-3 fatty acids, Plant sterols, Polyphenols, Responders

  2. Cardiorespiratory Fitness and Incidence of Type 2 Diabetes in United States Veterans on Statin Therapy.

    Science.gov (United States)

    Kokkinos, Peter; Faselis, Charles; Narayan, Puneet; Myers, Jonathan; Nylen, Eric; Sui, Xuemei; Zhang, Jiajia; Lavie, Carl J

    2017-10-01

    Impact of cardiorespiratory fitness on statin-related incidence of type 2 diabetes has not been assessed. We assessed the cardiorespiratory fitness and diabetes incidence association in dyslipidemic patients on statins. We identified dyslipidemic patients with a normal exercise test performed during 1986 and 2014 at the Veterans Affairs Medical Centers in Washington, DC or Palo Alto, Calif. The statin-treated patients (n = 4092; age = 58.8 ± 10.9 years) consisted of 2701 Blacks and 1391 Whites. None had evidence of type 2 diabetes prior to statin therapy. We formed 4 fitness categories based on age and peak metabolic equivalents achieved: Least-fit (n = 954), Low-fit (n = 1201), Moderate-fit (n = 1242), and High-fit (n = 695). The non-statin-treated cohort (n = 3001; age = 57.2 ± 11.2 years) with no evidence of type 2 diabetes prior to the exercise test served as controls. Diabetes incidence was 24% higher in statin-treated compared with non-statin-treated patients (P fit, adjusted risk decreased progressively with increasing fitness and was 34% lower for High-fit patients (hazard ratio [HR] 0.66; 95% confidence interval [CI], 0.53-0.82; P fit (HR 1.50; 95% CI, 1.30-1.73; P fit patients (HR 1.22; 95% CI, 1.06-1.41; P = .006). Risk of diabetes in statin-treated dyslipidemic patients was inversely and independently associated with cardiorespiratory fitness. The increased risk was evident only in relatively low-fitness patients. Improving fitness may modulate the potential diabetogenic effects of statins. Published by Elsevier Inc.

  3. The host response in critically ill sepsis patients on statin therapy: a prospective observational study.

    Science.gov (United States)

    Wiewel, Maryse A; Scicluna, Brendon P; van Vught, Lonneke A; Hoogendijk, Arie J; Zwinderman, Aeilko H; Lutter, René; Horn, Janneke; Cremer, Olaf L; Bonten, Marc J; Schultz, Marcus J; van der Poll, Tom

    2018-01-18

    Statins can exert pleiotropic anti-inflammatory, vascular protective and anticoagulant effects, which in theory could improve the dysregulated host response during sepsis. We aimed to determine the association between prior statin use and host response characteristics in critically ill patients with sepsis. We performed a prospective observational study in 1060 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013. Of these, 351 patients (33%) were on statin therapy before admission. The host response was evaluated by measuring 23 biomarkers providing insight into key pathways implicated in sepsis pathogenesis and by analyzing whole-blood leukocyte transcriptomes in samples obtained within 24 h after ICU admission. To account for indication bias, a propensity score-matched cohort was created (N = 194 in both groups for protein biomarkers and N = 95 in both groups for gene expression analysis). Prior statin use was not associated with an altered mortality up to 90 days after admission (38.0 vs. 39.7% in the non-statin users in the propensity-matched analysis). Statin use did not modify systemic inflammatory responses, activation of the vascular endothelium or the coagulation system. The blood leukocyte genomic response, characterized by over-expression of genes involved in inflammatory and innate immune signaling pathways as well as under-expression of genes associated to T cell function, was not different between patients with and without prior statin use. Statin therapy is not associated with a modified host response in sepsis patients on admission to the ICU.

  4. The association of statin therapy with the risk of recurrent venous thrombosis.

    Science.gov (United States)

    Smith, N L; Harrington, L B; Blondon, M; Wiggins, K L; Floyd, J S; Sitlani, C M; McKnight, B; Larson, E B; Rosendaal, F R; Heckbert, S R; Psaty, B M

    2016-07-01

    Essentials A lowered risk of recurrent venous thrombosis (VT) with statin treatment is controversial. Among observational inception cohort of 2,798 adults with incident VT, 457 had recurrent VT. Time-to-event models with time-varying statin use and adjustment for potential confounders was used for analysis. Compared to nonuse, current statin use was associated with 26% lower risk of recurrent VT. Click to hear Prof. Büller's perspective on Anticoagulant Therapy in the Treatment of Venous Thromboembolism Background Meta-analyses of randomized controlled trials suggest that treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lowers the risk of incident venous thrombosis (VT), particularly among those without prevalent clinical cardiovascular disease (CVD). Whether this is true for the prevention of recurrent VT is debated. We used an observational inception cohort to estimate the association of current statin use with the risk of recurrent VT. Methods and Results The study setting was a large healthcare organization with detailed medical record and pharmacy information at cohort entry and throughout follow-up. We followed 2798 subjects 18-89 years of age who experienced a validated incident VT between January 1, 2002, and December 31, 2010, for a first recurrent VT, validated by medical record review. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT: hazard ratio 0.74, 95% confidence interval 0.59-0.94. Among cohort members free of CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT: hazard ratio 0.62, 95% confidence interval 0.45-0.85. We found similar results when restricting to new users of statins and in subgroups of different statin types and doses. Conclusions In a population-based cohort of subjects who had

  5. Impact of statins and beta-blocker therapy on mortality after coronary artery bypass graft surgery

    Science.gov (United States)

    Blackstone, Eugene; Kapadia, Samir R.

    2015-01-01

    Background We conducted a retrospective cohort study of patients after first-time isolated coronary artery bypass graft surgery (CABG) and assessed the impact of a discharge regimen including beta-blockers and statin therapy and their relationship to long-term all cause mortality and major adverse cardiovascular events (MACE). Methods We identified patients age >18 years, undergoing first time isolated CABG from 1993 to 2005. Patients were identified using the Cardiovascular Information Registry (CVIR). We collected follow-up information at 30, 60, 90 days and yearly follow-up. The registry is approved for use in research by the institutional review broad. Results We identified 5,205 patients who underwent single isolated CABG between January 1993 and December 2005. The mean age was 64.5±9.7 years and over 70% were male. There was a significant difference in the low density lipoproteins (LDL) concentration between those with or without statin medications (134±41.9 mg/dL) (no statin) vs. 126±44.8 mg/dL (with statin), P=0.001. A discharge regimen with statin therapy was associated with and overall reduction in 30 day, 1 year and long-term mortality. In addition, overall the triple ischemic endpoint of death, myocardial infarction (MI) and stroke was also significantly lower in the statin vs. no-statin group. In addition, statin and beta-blockers exerted synergistic effect on overall mortality outcomes short-term and in the long-term. We note that the predictors of overall death include no therapy with statin therapy and age [hazard ratios (HR) 1.1, 95% CI: 1.04-1.078, P<0.001] and presence of renal failure (HR 2.0, P=0.005). The estimated 11-year Kaplan Meier curves for mortality between the two groups starts to diverge immediately post discharge after single isolated CABG and continue to diverge through out the follow-up period. Conclusions A post-discharge regimen of statins independently reduces overall and 1 year mortality. These results confirm those of

  6. Statin therapy and clinical outcomes in myocardial infarction patients complicated by acute heart failure : insights from the EPHESUS trial

    NARCIS (Netherlands)

    Dobre, Daniela; Rossignol, Patrick; Murin, Jan; Parkhomenko, Alexander; Lamiral, Zohra; Krum, Henry; van Veldhuisen, Dirk J.; Pitt, Bertram; Zannad, Faiez

    Several clinical trials have shown that in patients with acute myocardial infarction (MI), statin therapy improves cardiovascular (CV) outcomes, but in these trials patients with acute heart failure (HF) were excluded or only a few were included. In patients with chronic HF, statin therapy does not

  7. Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia.

    Science.gov (United States)

    Maxwell, Whitney D; Ramsey, Laura B; Johnson, Samuel G; Moore, Kate G; Shtutman, Michael; Schoonover, John H; Kawaguchi-Suzuki, Marina

    2017-09-01

    Interindividual variability in response to 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, with regard to both efficacy and safety is an obvious target for pharmacogenetic research. Many genes have been identified as possible contributors to variability in statin response and safety. Genetic polymorphisms may alter the structure or expression of coded proteins, with potential impacts on lipid and statin absorption, distribution, metabolism, and elimination as well as response pathways related to the pharmacologic effect. Many studies have explored the variation in statins' pharmacokinetic and pharmacodynamic parameters; however, to our knowledge, few have established definitive relationships between the genetic polymorphisms and patient outcomes, such as cardiovascular events. In this review article, we provide a statin-based summary of available evidence describing pharmacogenetic associations that may be of clinical relevance in the future. Although currently available studies are often small or retrospective, and may have conflicting results, they may be useful in providing direction for future confirmatory studies and may point to associations that could be confirmed in the future when more patient outcomes-based studies are available. We also summarize the clinically relevant evidence currently available to assist clinicians with providing personalized pharmacotherapy for patients requiring statin therapy. © 2017 Pharmacotherapy Publications, Inc.

  8. Case report of exercise and statin-fibrate combination therapy-caused myopathy in a patient with metabolic syndrome: contradictions between the two main therapeutic pathways.

    Science.gov (United States)

    László, Andrea; Kalabay, László; Nemcsik, János

    2013-02-06

    Lifestyle modifications including exercise are beneficial and fundamentally part of the therapy of metabolic syndrome, although in most of the cases medical interventions are also required to reach the target values in the laboratory parameters. Statin and fibrate combination therapy is considered to be safe and effective in dyslipidaemia and metabolic syndrome. However, increased physical activity can enhance the statin and fibrate-associated myopathy. Myositis and the rare but life-threatening rhabdomyolysis are causing a conflict between exercise and statin-fibrate therapy, which is yet to be resolved. We present a case of a 43-year-old Caucasian man with metabolic syndrome who had the side-effect of exercise and drug-associated myositis. The patient had only transient moderate complaints and rhabdomyolysis could be avoided with the one-month creatine kinase control, a test which is not recommended routinely by the new guidelines. We would like to turn the spotlight on the possible complications of statin-fibrate therapy and exercise, when strict follow-up is recommended. In this condition high number of patients can be affected and the responsibility of general practitioners is accentuated.

  9. Associations between statin use and progression in men with prostate cancer treated with primary androgen deprivation therapy

    DEFF Research Database (Denmark)

    Mikkelsen, Marta Kramer; Thomsen, Frederik Birkebæk; Berg, Kasper Drimer

    2017-01-01

    between statin use and risk of progression, HR 0.98 (95% CI: 0.72-1.32). In competing risk analyses the 5-year cumulative incidence of progression was 55% (95% CI: 46-64%) for statin users and 62% (95% CI: 57-67%) for non-statin users, p = 0.11. CONCLUSION: In the current study, statin use at time of PCa......INTRODUCTION: In several observational studies, statin use has been associated with reduced risk of progression and mortality in men with prostate cancer (PCa). The study aim was to investigate the association between statin use at time of PCa diagnosis and time to PCa progression in men...... with advanced or metastatic PCa receiving androgen deprivation therapy (ADT) as primary treatment. PATIENTS AND METHODS: The study population consisted of all men receiving ADT as primary therapy at two Danish Urological Departments in 2007-2013. The primary outcome was time to progression defined as castration...

  10. Personalized Prediction of Lifetime Benefits with Statin Therapy for Asymptomatic Individuals: A Modeling Study

    NARCIS (Netherlands)

    B.S. Ferket (Bart); B.J.H. van Kempen (Bob); J. Heeringa (Jan); S. Spronk (Sandra); K.E. Fleischmann (Kirsten); R.L. Nijhuis (Rogier); A. Hofman (Albert); E.W. Steyerberg (Ewout); M.G.M. Hunink (Myriam)

    2012-01-01

    textabstractBackground: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes.

  11. Lipophilic versus hydrophilic statin therapy for heart failure: a protocol for an adjusted indirect comparison meta-analysis

    Science.gov (United States)

    2013-01-01

    Background Statins are known to reduce cardiovascular morbidity and mortality in primary and secondary prevention studies. Subsequently, a number of nonrandomised studies have shown statins improve clinical outcomes in patients with heart failure (HF). Small randomised controlled trials (RCT) also show improved cardiac function, reduced inflammation and mortality with statins in HF. However, the findings of two large RCTs do not support the evidence provided by previous studies and suggest statins lack beneficial effects in HF. Two meta-analyses have shown statins do not improve survival, whereas two others showed improved cardiac function and reduced inflammation in HF. It appears lipophilic statins produce better survival and other outcome benefits compared to hydrophilic statins. But the two types have not been compared in direct comparison trials in HF. Methods/design We will conduct a systematic review and meta-analysis of lipophilic and hydrophilic statin therapy in patients with HF. Our objectives are: 1. To determine the effects of lipophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation. 2. To determine the effects of hydrophilic statins on (1) mortality, (2) hospitalisation for worsening HF, (3) cardiac function and (4) inflammation. 3. To compare the efficacy of lipophilic and hydrophilic statins on HF outcomes with an adjusted indirect comparison meta-analysis. We will conduct an electronic search of databases for RCTs that evaluate statins in patients with HF. The reference lists of all identified studies will be reviewed. Two independent reviewers will conduct the search. The inclusion criteria include: 1. RCTs comparing statins with placebo or no statin in patients with symptomatic HF. 2. RCTs that employed the intention-to-treat (ITT) principle in data analysis. 3. Symptomatic HF patients of all aetiologies and on standard treatment. 4. Statin of any dose as intervention. 5. Placebo or no

  12. Randomized Controlled Trial of Early Versus Delayed Statin Therapy in Patients With Acute Ischemic Stroke: ASSORT Trial (Administration of Statin on Acute Ischemic Stroke Patient).

    Science.gov (United States)

    Yoshimura, Shinichi; Uchida, Kazutaka; Daimon, Takashi; Takashima, Ryuzo; Kimura, Kazuhiro; Morimoto, Takeshi

    2017-11-01

    Several studies suggested that statins during hospitalization were associated with better disability outcomes in patients with acute ischemic stroke, but only 1 small randomized trial is available. We conducted a multicenter, open-label, randomized controlled trial in patients with acute ischemic strokes in 11 hospitals in Japan. Patients with acute ischemic stroke and dyslipidemia randomly received statins within 24 hours after admission in the early group or on the seventh day in the delayed group, in a 1:1 ratio. Statins were administered for 12 weeks. The primary outcome was patient disability assessed by modified Rankin Scale at 90 days. A total of 257 patients were randomized and analyzed (early 131, delayed 126). At 90 days, modified Rankin Scale score distribution did not differ between groups ( P =0.68), and the adjusted common odds ratio of the early statin group was 0.84 (95% confidence interval, 0.53-1.3; P =0.46) compared with the delayed statin group. There were 3 deaths at 90 days (2 in the early group, 1 in the delayed group) because of malignancy. Ischemic stroke recurred in 9 patients (6.9%) in the early group and 5 patients (4.0%) in the delayed group. The safety profile was similar between groups. Our randomized trial involving patients with acute ischemic stroke and dyslipidemia did not show any superiority of early statin therapy within 24 hours of admission compared with delayed statin therapy 7 days after admission to alleviate the degree of disability at 90 days after onset. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02549846. © 2017 American Heart Association, Inc.

  13. Risk factors associated with atherogenic dyslipidemia in the presence of optimal statin therapy.

    Science.gov (United States)

    Zhao, Wang; Zheng, Xi-Long; Jiang, Ze-Nan; Liao, Xiao-Bo; Zhao, Shui-Ping

    2017-12-01

    This study investigated the prevalence of atherogenic dyslipidemia (AD) in Chinese outpatients whose low-density lipoprotein cholesterol (LDL-C) levels reached the goals with statin monotherapy and evaluated the characteristics of these patients. An analysis of the Dyslipidemia International Survey-China study that was carried out at 122 hospitals in China. Among patients reaching their LDL-C goals, the presence of AD was defined as triglyceride levels ≥1.7mmol/L and/or low levels of high-density lipoprotein cholesterol (men: dyslipidemia, 13,551 patients reached LDL-C goals, and 7719 patients of them had AD. Age, male gender, BMI, sedentary lifestyle, coronary heart disease, serum uric acid levels, and fasting plasma glucose (all P<0.05) were independently associated with AD. The intensity of statin therapy did not affect the prevalence of AD. There was a high prevalence of AD in Chinese patients with optimal statin treatment. Some risk factors associated with AD were identified, but these factors were slightly different according to two criteria/guidelines. The intensity of statin therapy did not reduce the prevalence of AD. A combination lipid therapy may be more suitable for Chinese patients. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  14. Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with Myocardial Infarction and Abnormal Glucose Tolerance

    DEFF Research Database (Denmark)

    Auscher, Søren; Løgstrup, Brian Bridal; Møller, Jacob Eifer

    2017-01-01

    OBJECTIVES: Abnormal glucose tolerance in patients with acute myocardial infarction (AMI) is associated with greater mortality and adverse cardiovascular effects. As statins possess a range of beneficial pleiotropic effects on the cardiovascular system, we sought to assess the cardioprotective...... effects of statins on left ventricular function in patients with AMI in relation to glycometabolic state. METHODS: In a prospective, randomized trial, 140 patients with AMI were randomized to intensive statin therapy receiving statin loading with 80 mg of rosuvastatin followed by 40 mg daily or standard...... statin therapy. Patients were assessed with an oral glucose tolerance test and their left ventricular (LV) function was assessed with speckle-tracking echocardiography measuring regional longitudinal systolic strain (RLSS) in the infarct area. RESULTS: Overall RLSS in the infarct area improved by a mean...

  15. Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study.

    Directory of Open Access Journals (Sweden)

    Bart S Ferket

    Full Text Available BACKGROUND: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD. However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks. METHODS AND FINDINGS: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1 a web-based calculator for gains in total and CVD-free life expectancy and (2 color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE charts. In 2,428 participants (mean age 67.7 y, 35.5% men, statin therapy increased total life expectancy by 0.3 y (SD 0.2 and CVD-free life expectancy by 0.7 y (SD 0.4. Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk. CONCLUSIONS: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the

  16. Fat-Free Mass and Fasting Glucose Values in Patients with and without Statin Therapy Assigned to Age Groups between 75 Years

    Directory of Open Access Journals (Sweden)

    Alexander Dzien

    2013-02-01

    Full Text Available Objective: The aging-associated changes in body composition result in an increased cardiometabolic risk. A tremendous reduction of cardiovascular morbidity and mortality can be obtained by statin therapy. Statins are well tolerated, with myopathy as the most serious negative side effect. Some recently published studies indicate that the incidence of type 2 diabetes might be increased during intensified statin therapy. The aim of our study was to investigate whether statin therapy has an influence on the aging-associated changes in fat-free mass (FFM. Methods: A total of 3,280 persons attending a medical outdoor center between January 2005 and July 2011 were assigned to 3 age groups from 75 years. Clinical data, body mass index (BMI, and body composition were evaluated in the different age groups in patients with and without statin therapy. To analyze the impact of statin use on FFM, we regressed a patient's FFM on an interaction term between statin use and age and other control variables. Results: Aging was associated with a decrease in BMI and FFM, while fat mass continuously increased up to the age of >75 years. This was paralleled by a continuous increase in fasting glucose levels in patients with and without statin therapy. The loss of FFM between the age group 75 years was more pronounced in statin-treated patients (10.88% than in non-statin users (8.47%. Creatine phosphokinase values revealed a decrease of 7.77 U/l between the age groups 75 years in non-statin users and of 14.75 U/l in statin users. Statistical analysis indicated that the effect of statin therapy on FFM is more pronounced in younger than in older patients. Conclusions: Patients under statin therapy seem to be more vulnerable to the aging-associated lowering of FFM. Diagnostic procedures and interventions to prevent a loss of muscle mass might be of particular advantage in elderly patients under statin therapy.

  17. Synergistic effect of statins and postmenopausal hormone therapy in the prevention of skeletal fractures in elderly women.

    Science.gov (United States)

    Bakhireva, Ludmila N; Shainline, Michael R; Carter, Shelley; Robinson, Scott; Beaton, Sarah J; Nawarskas, James J; Gunter, Margaret J

    2010-09-01

    To examine the role of concurrent 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) use and postmenopausal hormone therapy on osteoporosis-related fractures. Case-control study. Data Source. Large integrated health plan in New Mexico. Patients. Case patients were 1001 women with incident fractures of the hip, wrist, forearm, or spine that occurred between January 1, 2000, and December 31, 2005, and controls were 2607 women without fractures during the same time frame; both groups were selected from the same population of women aged 50 years or older who utilized health plan services during the study time frame. Postmenopausal hormone therapy use was classified as "current" (12 mo before index date) or "never or past." The risk of fractures was ascertained among continuous (> or = 80% medication possession ratio during 12 mo before the index date) and current (3 mo before index date) statin users relative to patients without hyperlipidemia who did not use lipid-lowering drugs. The interaction between statins and hormone therapy was examined in multivariable logistic regression. The association between statin use and fractures was examined separately among current and never or past hormone therapy users after controlling for other risk factors. Nineteen percent of the study participants were current hormone therapy users; 9.5% were current and 4.8% were continuous statin users. No association between continuous statin use and fractures was observed among never or past hormone therapy users (odds ratio [OR] 0.80, 95% confidence interval [CI] 0.53-1.22). In contrast, a strong protective effect (OR 0.19, 95% CI 0.04-0.87) was observed among women who concurrently used statins and hormone therapy for 1 year, independent of age; corticosteroid, bisphosphonate, thiazide diuretic, calcitonin, methotrexate, or antiepileptic drug use; chronic kidney disease; and Charlson comorbidity index. Concurrent statin use and hormone therapy may have a synergistic

  18. Effect of high-intensity statin therapy on atherosclerosis in non-infarct-related coronary arteries (IBIS-4)

    DEFF Research Database (Denmark)

    Räber, Lorenz; Taniwaki, Masanori; Zaugg, Serge

    2015-01-01

    AIM: The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition, and phen......AIM: The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition......-infarct-related epicardial coronary arteries (non-IRA) after successful primary PCI. Patients were treated with high-intensity rosuvastatin (40 mg/day) throughout 13 months and serial intracoronary imaging with the analysis of matched segments was available for 82 patients with 146 non-IRA. The primary IVUS end...

  19. [Statins and muscle pain].

    Science.gov (United States)

    Yosef, Yoni; Schurr, Daniel; Constantini, Naama

    2014-07-01

    Statins are used for the prevention and treatment of cardiovascular disease. The treatment is quite safe but not free of side effects, particularly muscle pain. Fear of pain may prevent patients from carrying out exercise or diminish their motivation to return and engage in it, even though both the statins and the exercise have a proven benefit in both treatment and prevention, and a synergistic effect enhances this benefit. Prevalence of muscular pain ranges from 1-30%. Pain usually appears at the beginning of treatment, but can occur even after months and under any of the existing agents. The creatine phosphokinase (CPK) enzyme level may rise, but not necessarily. Increases to exceptional values (10 times the upper normal level) are relatively rare and rhabdomyolysis is extremely rare. The risk increases with age, co-morbidities and especially when taken concurrently with drugs that are metabolized in a similar pathway. Pain usually passes within a month after discontinuing treatment, but may persist for six months or more. Studies have examined the effect of statin therapy on the ability to perform physical activity, but results are inconsistent. The increased rise of CPK was observed under statin therapy, a tendency that increased with age. However, it was not accompanied by an increased incidence of muscle pain or rhabdomyolysis. Considering the above we recommend encouraging patients to exercise. However, patients should be instructed to report new or worsening muscular pains. Discontinuation, lowering dose or replacement should be considered when pain is suspected to be related with treatment.

  20. Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zaorsky, Nicholas G. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Buyyounouski, Mark K., E-mail: mark.buyyounouski@fccc.edu [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Li, Tianyu [Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Horwitz, Eric M. [Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States)

    2012-09-01

    Purpose: To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT). Methods and Materials: Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which has been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the {chi}{sup 2} test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression. Results: The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months. Conclusions: In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative

  1. Aspirin and Statin Nonuse Associated With Early Biochemical Failure After Prostate Radiation Therapy

    International Nuclear Information System (INIS)

    Zaorsky, Nicholas G.; Buyyounouski, Mark K.; Li, Tianyu; Horwitz, Eric M.

    2012-01-01

    Purpose: To present the largest retrospective series investigating the effect of aspirin and statins, which are hypothesized to have antineoplastic properties, on biochemical failure (nadir plus 2 ng/mL) after prostate radiation therapy (RT). Methods and Materials: Between 1989 and 2006, 2051 men with clinically localized prostate cancer received definitive RT alone (median dose, 76 Gy). The rates of aspirin use and statin use (defined as any use at the time of RT or during follow-up) were 36% and 34%, respectively. The primary endpoint of the study was an interval to biochemical failure (IBF) of less than 18 months, which has been shown to be the single strongest predictor of distant metastasis, prostate cancer survival, and overall survival after RT. Patient demographic characteristics and tumor staging factors were assessed with regard to associations with the endpoint. Univariate analysis was performed with the χ 2 test for categorical variables and the Wilcoxon test for continuous variables. Multivariable analysis was performed with a multiple logistic regression. Results: The median follow-up was 75 months. Univariate analysis showed that an IBF of less than 18 months was associated with aspirin nonuse (P<.0001), statin nonuse (P<.0001), anticoagulant nonuse (P=.0006), cardiovascular disease (P=.0008), and prostate-specific antigen (continuous) (P=.008) but not with Gleason score, age, RT dose, or T stage. On multivariate analysis, only aspirin nonuse (P=.0012; odds ratio, 2.052 [95% confidence interval, 1.328-3.172]) and statin nonuse (P=.0002; odds ratio, 2.465 [95% confidence interval, 1.529-3.974]) were associated with an IBF of less than 18 months. Conclusions: In patients who received RT for prostate cancer, aspirin or statin nonuse was associated with early biochemical failure, a harbinger of distant metastasis and death. Further study is needed to confirm these findings and to determine the optimal dosing and schedule, as well as the relative

  2. The preventive effect of statin therapy on new-onset and recurrent atrial fibrillation in patients not undergoing invasive cardiac interventions ☆

    DEFF Research Database (Denmark)

    Bang, Casper Niels Furbo; Greve, Anders M; Abdulla, Jawdat

    2013-01-01

    BACKGROUND: Previous meta-analyses suggest that pre-procedural use of statin therapy may reduce atrial fibrillation (AF) following invasive cardiac interventions (coronary artery by-pass grafting and percutaneous coronary intervention). However, the current evidence on the benefit of statins...... unrelated to invasive cardiac interventions has not been clarified systematically. METHODS: Through a systematic literature search, trials examining the effect of statin therapy on AF were selected. Trials using statins before any percutaneous or surgical cardiac interventions were excluded. RESULTS......: The search identified 11 randomized and 16 observational eligible studies, totaling 106,640 patients receiving statin therapy and 129,305 serving as controls. Fourteen studies investigated the effect of statins on new-onset AF, 13 studies investigated the effect of statins on recurrent AF and one in both new...

  3. Ultrasound Assessment of Carotid Plaque Echogenicity Response to Statin Therapy: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Ibrahimi, Pranvera; Jashari, Fisnik; Bajraktari, Gani; Wester, Per; Henein, Michael Y.

    2015-01-01

    Objective: To evaluate in a systematic review and meta-analysis model the effect of statin therapy on carotid plaque echogenicity assessed by ultrasound. Methods: We have systematically searched electronic databases (PubMed, MEDLINE, EMBASE and Cochrane Center Register) up to April, 2015, for studies evaluating the effect of statins on plaque echogenicity. Two researchers independently determined the eligibility of studies evaluating the effect of statin therapy on carotid plaque echogenicity that used ultrasound and grey scale median (GSM) or integrated back scatter (IBS). Results: Nine out of 580 identified studies including 566 patients’ carotid artery data were meta-analyzed for a mean follow up of 7.2 months. A consistent increase in the echogenicity of carotid artery plaques, after statin therapy, was reported. Pooled weighted mean difference % (WMD) on plaque echogenicity after statin therapy was 29% (95% CI 22%–36%), p < 0.001, I2 = 92.1%. In a meta-regression analysis using % mean changes of LDL, HDL and hsCRP as moderators, it was shown that the effects of statins on plaque echogenicity were related to changes in hsCRP, but not to LDL and HDL changes from the baseline. The effect of statins on the plaque was progressive; it showed significance after the first month of treatment, and the echogenicity continued to increase in the following six and 12 months. Conclusions: Statin therapy is associated with a favorable increase of carotid plaque echogenicity. This effect seems to be dependent on the period of treatment and hsCRP change from the baseline, independent of changes in LDL and HDL. PMID:25984600

  4. Statin therapy and plasma vitamin E concentrations: A systematic review and meta-analysis of randomized placebo-controlled trials.

    Science.gov (United States)

    Sahebkar, Amirhossein; Simental-Mendía, Luis E; Ferretti, Gianna; Bacchetti, Tiziana; Golledge, Jonathan

    2015-12-01

    Vitamin E is one of the most important natural antioxidants, and its plasma levels are inversely associated with the progression of atherosclerosis. There have been reports suggesting a potential negative effect of statin therapy on plasma vitamin E levels. The aim of this meta-analysis was to determine the impact of statin therapy on plasma vitamin E concentrations. PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched to identify randomized placebo-controlled trials evaluating the impact of statins on plasma vitamin E concentrations from inception to February 27, 2015. A systematic assessment of bias in the included studies was performed using the Cochrane criteria. A random-effects model (using DerSimonian-Laird method) and the generic inverse variance method were used to examine the effect of statins on plasma vitamin E concentrations. Heterogeneity was quantitatively assessed using the I(2) index. Sensitivity analysis was conducted using the leave-one-out method. A meta-analysis of data from 8 randomized treatment arms including 504 participants indicated a significant reduction in plasma vitamin E concentrations following statin treatment (WMD: -16.30%, 95% CI: -16.93, -15.98, p statin therapy (WMD: 29.35%, 95% CI: 24.98, 33.72, p Statin therapy was not associated with any significant alteration in LDL vitamin E content (SMD: 0.003, 95% CI: -0.90, 0.90, p = 0.995). Findings of the present study suggest that statin therapy has no negative impact on plasma vitamin E concentrations or LDL vitamin E content. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Safety of statins

    Directory of Open Access Journals (Sweden)

    Debasish Maji

    2013-01-01

    Full Text Available Statins are an established class of drugs with proven efficacy in cardiovascular risk reduction. The concern over statin safety was first raised with the revelation of myopathy and rhabdomyolysis with the use of now withdrawn cerivastatin. Enhanced understanding of the mechanisms behind adverse effects of statins including an insight into the pharmacokinetic properties have minimised fear of statin use among clinicians. Studies reveal that occurrence of myopathy and rhabdomyolysis are rare 1/100000 patient-years. The risk of myopathy/rhabdomyolysis varies between statins due to varying pharmacokinetic profiles. This explains the differing abilities of statins to adverse effects and drug interaction potentials that precipitate adverse effects. Higher dose of rosuvastatin (80 mg/day was associated with proteinuria and hematuria while lower doses were devoid of such effects. Awareness of drugs interacting with statins and knowledge of certain combinations such as statin and fibrates together with monitoring of altered creatine kinase activity may greatly minimise associated adverse effects. Statins also asymptomatically raise levels of hepatic transaminases but are not correlated with hepatotoxicity. Statins are safe and well tolerated including more recent potent statins such as, rosuvastatin. The benefits of intensive statin use in cardiovascular risk reduction greatly outweigh risks. The present review discusses underlying causes of statin-associated adverse effects including management in high risk groups.

  6. Statin Intolerance: the Clinician's Perspective.

    Science.gov (United States)

    Stulc, Tomáš; Ceška, Richard; Gotto, Antonio M

    2015-12-01

    Muscle problems and other adverse symptoms associated with statin use are frequent reasons for non-adherence and discontinuation of statin therapy, which results in inadequate control of hyperlipidemia and increased cardiovascular risk. However, most patients who experience adverse symptoms during statin use are able to tolerate at least some degree of statin therapy. Given the profound cardiovascular benefits derived from statins, an adequate practical approach to statin intolerance is, therefore, of great clinical importance. Statin intolerance can be defined as the occurrence of myalgia or other adverse symptoms that are attributed to statin therapy and that lead to its discontinuation. In reality, these symptoms are actually unrelated to statin use in many patients, especially in those with atypical presentations following long periods of treatment. Thus, the first step in approaching patients with adverse symptoms during the course of statin therapy is identification of those patients for whom true statin intolerance is unlikely, since most of these patients would probably be capable of tolerating adequate statin therapy. In patients with statin intolerance, an altered dosing regimen of very low doses of statins should be attempted and, if tolerated, should gradually be increased to achieve the highest tolerable doses. In addition, other lipid-lowering drugs may be needed, either in combination with statins, or alone, if statins are not tolerated at all. Stringent control of other risk factors can aid in reducing cardiovascular risk if attaining lipid treatment goals proves difficult.

  7. [Consensus for pharmacologic treatment of atherogenic dyslipidemia with statin-fenofibrate combined therapy].

    Science.gov (United States)

    2016-01-01

    LDLc levels are associated with increase of cardiovascular risk, and statins are currently used for their control. Nevertheless, a despite of LDLc levels at goal, a residual risk is persistent, commonly associated with persistent lipids modifications (high triglycerides and low HDLc). So, it is necessary to evaluate triglycerides and HDL to assessment cardiovascular risk. Clinical data are consistent with efficacy and safety of combination therapy with statin and other lipid lowering drugs, for instance fenofibrate. Patients with hipertriglyceridemia and low HDLc are the group with most potential improve. In that patients with atherogenic dyslipidemia, the target for therapeutic objectives related with non-HDL-cholesterol is a priority, because non-HDL-cholesterol is considered as a more accuracy measure to assessment cardiovascular risk. Copyright © 2015. Published by Elsevier España.

  8. Clinical Effectiveness of Statin Therapy After Ischemic Stroke: Primary Results From the Statin Therapeutic Area of the Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) Study.

    Science.gov (United States)

    O'Brien, Emily C; Greiner, Melissa A; Xian, Ying; Fonarow, Gregg C; Olson, DaiWai M; Schwamm, Lee H; Bhatt, Deepak L; Smith, Eric E; Maisch, Lesley; Hannah, Deidre; Lindholm, Brianna; Peterson, Eric D; Pencina, Michael J; Hernandez, Adrian F

    2015-10-13

    In patients with ischemic stroke, data on the real-world effectiveness of statin therapy for clinical and patient-centered outcomes are needed to better inform shared decision making. Patient-Centered Research Into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) is a Patient-Centered Outcomes Research Institute-funded research program designed with stroke survivors to evaluate the effectiveness of poststroke therapies. We linked data on patients ≥65 years of age enrolled in the Get With The Guidelines-Stroke Registry to Medicare claims. Two-year to postdischarge outcomes of those discharged on a statin versus not on a statin were adjusted through inverse probability weighting. Our coprimary outcomes were major adverse cardiovascular events and home time (days alive and out of a hospital or skilled nursing facility). Secondary outcomes included all-cause mortality, all-cause readmission, cardiovascular readmission, and hemorrhagic stroke. From 2007 to 2011, 77 468 patients who were not taking statins at the time of admission were hospitalized with ischemic stroke; of these, 71% were discharged on statin therapy. After adjustment, statin therapy at discharge was associated with a lower hazard of major adverse cardiovascular events (hazard ratio, 0.91; 95% confidence interval, 0.87-0.94), 28 more home-time days after discharge (PStatin therapy at discharge was not associated with increased risk of hemorrhagic stroke (hazard ratio, 0.94; 95% confidence interval, 0.72-1.23). Among statin-treated patients, 31% received a high-intensity dose; after risk adjustment, these patients had outcomes similar to those of recipients of moderate-intensity statin. In older ischemic stroke patients who were not taking statins at the time of admission, discharge statin therapy was associated with lower risk of major adverse cardiovascular events and nearly 1 month more home time during the 2-year period after hospitalization. © 2015 American Heart Association

  9. Statin Therapy and Outcome After Ischemic Stroke: Systematic Review and Meta-Analysis of Observational Studies and Randomized Trials.

    LENUS (Irish Health Repository)

    2013-01-03

    Background-Although experimental data suggest that statin therapy may improve neurological outcome after acute cerebral ischemia, the results from clinical studies are conflicting. We performed a systematic review and meta-analysis investigating the relationship between statin therapy and outcome after ischemic stroke. METHODS: The primary analysis investigated statin therapy at stroke onset (prestroke statin use) and good functional outcome (modified Rankin score 0 to 2) and death. Secondary analyses included the following: (1) acute poststroke statin therapy (≤72 hours after stroke), and (2) thrombolysis-treated patients. RESULTS: The primary analysis included 113 148 subjects (27 studies). Among observational studies, statin treatment at stroke onset was associated with good functional outcome at 90 days (pooled odds ratio [OR], 1.41; 95% confidence interval [CI], 1.29-1.56; P<0.001), but not 1 year (OR, 1.12; 95% CI, 0.9-1.4; P=0.31), and with reduced fatality at 90 days (pooled OR, 0.71; 95% CI, 0.62-0.82; P<0.001) and 1 year (OR, 0.80; 95% CI, 0.67-0.95; P=0.01). In the single randomized controlled trial reporting 90-day functional outcome, statin treatment was associated with good outcome (OR, 1.5; 95% CI, 1.0-2.24; P=0.05). No reduction in fatality was observed on meta-analysis of data from 3 randomized controlled trials (P=0.9). In studies of thrombolysis-treated patients, an association between statins and increased fatality at 90 days was observed (pooled OR, 1.25; 95% CI, 1.02-1.52; P=0.03, 3 studies, 4339 patients). However, this association was no longer present after adjusting for age and stroke severity in the largest study (adjusted OR, 1.14; 95% CI, 0.90-1.44; 4012 patients). CONCLUSIONS: In the largest meta-analysis to date, statin therapy at stroke onset was associated with improved outcome, a finding not observed in studies restricted to thrombolysis-treated patients. Randomized trials of statin therapy in acute ischemic stroke are needed.

  10. The spectrum of statin therapy in hyperlipidemic children

    NARCIS (Netherlands)

    Rodenburg, J.; Vissers, M. N.; Trip, M. D.; Wiegman, A.; Bakker, H. D.; Kastelein, J. J. P.

    2004-01-01

    The recommended therapy of hypercholesterolemia in children consists of dietary modification and bile acid-binding resins. Unfortunately, the lipid-lowering efficacy of bile acid-binding resins is modest, and moreover, long-term compliance is poor because of side effects. In contrast,

  11. Hip circumference is associated with high density lipoprotein cholesterol response following statin therapy in hypertensive subjects.

    Science.gov (United States)

    Pio-Magalhães, J A; Ferreira-Sae, M C; Souza, F A; Grespan-Magossi, A M; Schreiber, R; Velloso, L A; Geloneze, B; Franchini, K G; Nadruz, W

    2011-10-01

    This report investigated the relationship between anthropometric measurements of body fat distribution and lipid response to statins in hypercholesterolemic hypertensive patients. We prospectively examined 129 subjects who used either simvastatin 20 mg/day (no.=83) or atorvastatin 10 mg/day (no.=46) for 3 months. Anthropometry included evaluation of body mass index, waist and hip circumferences, and waist-to-hip-ratio. Significant decreases in LDL (pcorrelation between waist circumference and HDLcholesterol levels was detected (r=-0.18; p=0.04). Conversely, a direct relationship between hip circumference and HDLcholesterol response to statins was found in the whole sample (r=0.24; p=0.006), while no other anthropometric measurement displayed significant correlation with lipid changes. The association between HDL-cholesterol response and hip circumference was further confirmed by stepwise regression analysis adjusted for baseline HDL-cholesterol levels, metabolic syndrome, body mass index, and waist circumference. Hip circumference, a surrogate marker of peripheral adiposity, is associated with HDL-cholesterol changes following statin therapy in hypertensive patients.

  12. MYOPATHY AS A SIDE EFFECT OF STATIN THERAPY: MECHANISMS OF DEVELOPMENT AND PROSPECTS FOR TREATMENT

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2015-01-01

    Full Text Available Statins are lipid-lowering drugs with proven efficacy that reduce cardiovascular risk and are well tolerated by most patients. Myopathy as a side effect of statin therapy is one of the most common reasons for their withdrawal. Its severity can range from asymptomatic increase of serum CPK to life-threatening rhabdomyolysis. Therefore it is necessary to remember about the possibility of its occurrence.The exact molecular mechanisms of muscle damage by statins are still unknown. Various hypotheses are suggested in this respect: fatty acid oxidation disorders, mitochondrial dysfunction, increased protein degradation in myocytes due to changes in atrogin-1 and ubiquitin activity, activation of autoimmune processes, intracellular depletion of essential metabolites, destabilization of cell membranes, impaired expression of genes involved in apoptosis and protein degradation. The theory that the reduction of intramuscular CoQ10 level is the cause of myopathy prevails. Additional intake of CoQ10 seems promising, but is not evidence-based.

  13. MYOPATHY AS A SIDE EFFECT OF STATIN THERAPY: MECHANISMS OF DEVELOPMENT AND PROSPECTS FOR TREATMENT

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2015-09-01

    Full Text Available Statins are lipid-lowering drugs with proven efficacy that reduce cardiovascular risk and are well tolerated by most patients. Myopathy as a side effect of statin therapy is one of the most common reasons for their withdrawal. Its severity can range from asymptomatic increase of serum CPK to life-threatening rhabdomyolysis. Therefore it is necessary to remember about the possibility of its occurrence.The exact molecular mechanisms of muscle damage by statins are still unknown. Various hypotheses are suggested in this respect: fatty acid oxidation disorders, mitochondrial dysfunction, increased protein degradation in myocytes due to changes in atrogin-1 and ubiquitin activity, activation of autoimmune processes, intracellular depletion of essential metabolites, destabilization of cell membranes, impaired expression of genes involved in apoptosis and protein degradation. The theory that the reduction of intramuscular CoQ10 level is the cause of myopathy prevails. Additional intake of CoQ10 seems promising, but is not evidence-based.

  14. Influence of Peripheral Artery Disease and Statin Therapy on Apolipoprotein Profiles

    Directory of Open Access Journals (Sweden)

    Andrew W. Gardner

    2013-01-01

    Full Text Available Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n=17 or untreated (n=12 with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P<0.05 and lower values of Lp-A-I:A-II (P<0.05 than controls. The PAD group taking statins had lower age-adjusted values for apoB (P<0.05, Lp-A-II:B:C:D:E (P<0.05, Lp-B:E + Lp-B:C:E (P<0.05, Lp-B:C (P<0.05, and Lp-A-I (P<0.05 than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.gov NCT00618670.

  15. Impact of Statin Therapy on the Blood Pressure-Lowering Efficacy of a Single-Pill Perindopril/Amlodipine Combination in Hypertensive Patients with Hypercholesterolemia.

    Science.gov (United States)

    Sirenko, Yuriy; Radchenko, Ganna

    2017-03-01

    Several lines of research indicate that statins can lower blood pressure (BP) independently of their lipid-lowering effects when used as monotherapy and in combination with antihypertensive agents. This short-term, open-label study examined whether statin therapy had a synergistic effect on the BP-lowering efficacy of perindopril/amlodipine in a subgroup of patients in the PERSPECTIVA study with concomitant hypertension and hypercholesterolemia, with or without statin at baseline. The PERSPECTIVA study recruited 732 adults with untreated or uncontrolled hypertension. This subgroup analysis of PERSPECTIVA included 587 patients with concomitant hypertension and hypercholesterolemia (mean age 56.7 years) of whom 226 were receiving a statin at baseline (statin [+] group) and 361 were not (statin [-] group). All patients received treatment with single-pill combination perindopril/amlodipine at a dose of 5/5, 10/5 or 10/10 mg/day. The study duration was 60 days with follow-up visits for BP monitoring at 7, 15, 30 and 60 days. At day 60, BP control (statin [+] vs statin [-] group: 73 vs 64% respectively (+14%, P statin [+] group, the single-pill perindopril/amlodipine combination significantly reduced BP in patients previously untreated (n = 18), or treated with monotherapy (n = 97), dual therapy (n = 93), or triple therapy (n = 18): -38.8/-20.0, -39.1/-20.1, -38.0/-19.4, -39.9/-18.3 mmHg respectively (P statin [+] group (0.9%) vs the statin [-] group (2.5%). BP control rates in patients with uncontrolled hypertension and concomitant hypercholesterolemia are significantly improved with a treatment regimen that combines perindopril/amlodipine with statin therapy, regardless of previous antihypertensive therapy. This subanalysis of the PERSPECTIVA study supports the synergistic BP-lowering effect of statins and perindopril/amlodipine.

  16. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes

    DEFF Research Database (Denmark)

    Cannon, Christopher P; Blazing, Michael A; Giugliano, Robert P

    2015-01-01

    . METHODS: We conducted a double-blind, randomized trial involving 18,144 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and had LDL cholesterol levels of 50 to 100 mg per deciliter (1.3 to 2.6 mmol per liter) if they were receiving lipid-lowering therapy...... was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalization, coronary revascularization (≥30 days after randomization), or nonfatal stroke. The median follow-up was 6 years. RESULTS: The median time-weighted average LDL cholesterol level during the study...

  17. Long-term statin therapy in patients with systolic heart failure and normal cholesterol: effects on elevated serum markers of collagen turnover, inflammation, and B-type natriuretic peptide.

    LENUS (Irish Health Repository)

    Abulhul, Esam

    2012-01-01

    The role of statin therapy in heart failure (HF) is unclear. The amino-terminal propeptide of procollagen type III (PIIINP) predicts outcome in HF, and yet there are conflicting reports of statin therapy effects on PIIINP.

  18. [The lipid-regulating effect and safety of combined statin and bezafibrate therapy in acute coronary syndrome patients complicating with dyslipidemia].

    Science.gov (United States)

    Li, Xiang-ping; Gong, Hai-rong; Zhao, Shui-ping; Huang, Wen-yu

    2013-12-01

    To investigate the lipid-regulating effect and safety of combined statin and bezafibrate therapy in acute coronary syndrome(ACS) patients complicating with dyslipedemia. One hundred and four hospitalized patients with established ACS and increased serum triglycerides (TG) levels and/or low serum levels of high density lipoprotein cholesterol (HDL-C) were selected. Except for conventional therapy, the patients were randomly divided into 2 groups: control group (n = 52), treated with atorvastatin 20 mg qn or other statin equivalent to 20 mg atorvastatin; treatment group (n = 52), treated with the same dose statin plus bezafibrate 200 mg bid. The serum levels of total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C) and HDL-C were assessed before and after 6 and 12 weeks treatment, side effects and adverse events were recorded. After 6 weeks treatment, the serum levels of TC, TG and LDL-C in two groups were significantly reduced compared to baseline (all P 0.05). After 12 weeks, the rates reaching to target goals of LDL-C, TG, HDL-C, and non-HDL-C levels in the treatment group (69.2%, 88.5%, 92.3%, 46.2% and 65.4%, respectively) were significantly higher than those in the control group (34.6%, 65.4%, 46.2%, 7.7% and 42.3%, respectively, all P < 0.05). No serious side effects were observed in the two groups during the treatment period. The combined statin and bezafibrate treatment is safe and could increase the ratios of reaching target lipid levels in ACS patients complicating with increased TG and (or) decreased HDL-C.

  19. Statin Intolerance: A Literature Review and Management Strategies.

    Science.gov (United States)

    Saxon, David R; Eckel, Robert H

    Statin intolerance is a commonly encountered clinical problem for which useful management strategies exist. Although many patients report statin-related muscle symptoms, studies indicate that the majority of these patients can tolerate a statin upon re-challenge. Alternative statin dosing strategies are an effective way to modify and reintroduce statin therapy for patients reporting adverse symptoms. Correction of vitamin D deficiency and hypothyroidism may improve statin tolerability in some patients. CoQ10 supplementation has been found to be of no benefit for statin-related muscle symptoms in most recent clinical trials. PCSK9 inhibitors are a new therapeutic option that if confirmed as safe and effective by outcomes trials may be of substantial benefit to select patients at high ASCVD risk who are unable to achieve adequate low-density lipoprotein cholesterol (LDL-C) lowering on maximally tolerated statin therapy. Other available medications to lower LDL-C in statin intolerant patients include ezetimibe, bile acid sequestrants, niacin, and fibrates. Published by Elsevier Inc.

  20. Understanding Patient Adherence and Concerns with STatins and MedicatION Discussions with Physicians (ACTION): A Survey on the Patient Perspective of Dialogue with Healthcare Providers Regarding Statin Therapy.

    Science.gov (United States)

    Brinton, Eliot A

    2018-05-10

    Statin therapy is used first-line for cholesterol lowering and prevention of atherosclerotic cardiovascular disease (CVD), but side effects and the potential for drug-drug interactions may complicate its use. Provider-patient communication is essential for shared decision-making, which, in turn, is recommended by guidelines to reduce or overcome these challenges. Unfortunately, relatively little is known about provider-patient communication surrounding statin use. We conducted an online survey of 5,014 patients, U.S. residents over age 45 years, who had been prescribed a statin for hypercholesterolemia, to learn their perspectives on their disease state, medication use, side effects and, most importantly, recall of communication with their provider, especially at the time they were first diagnosed with hypercholesterolemia. Results were weighted to reflect the racial/ethnic composition of the general U.S. Ninety-four percent of patients said they were currently taking a statin and 6% said they had stopped. Past users vs current users were more likely to be female (64% vs 47%), younger than age 65 (57% vs 49%), and to have fewer CVD-related comorbidities (hypertension 58% vs 69%, Type 2 diabetes 17% vs 27%, and coronary heart disease 4% vs 9%, respectively; all pright statin," but 73% and 76%, respectively, said the choice of their statin was made with little or no input from them. Further, among current users, only 45% said that they communicate "openly" with their provider about statin-related challenges, and 39% said they usually don't ask questions about their statin. Forty-three percent of current users had switched a statin at least once and 47% of past statin users had switched statins at least once before stopping. Current users were more likely than past users to switch due to "it was recommended" (27% vs 8%), medication costs (14 vs 7%), lack of insurance coverage (10% vs 2%), desire for a generic statin (14 vs 2%), lack of cholesterol efficacy (13% vs 6

  1. The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials

    NARCIS (Netherlands)

    Sahebkar, Amirhossein; Serban, Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P.; Undas, Anetta; Lip, Gregory Y. H.; Bittner, Vera; Ray, Kausik; Watts, Gerald F.; Hovingh, G. Kees; Rysz, Jacek; Kastelein, John J. P.; Banach, Maciej

    2016-01-01

    Increased plasma levels of von Willebrand factor antigen (vWF:Ag) are associated with high risk of coronary artery disease. The effect of statin therapy on vWF:Ag levels remains uncertain. Therefore the aim of this meta-analysis was to evaluate the effect of statin therapy on vWF:Ag Levels. A

  2. The impact of statin therapy on long-term cardiovascular outcomes in an outpatient cardiology practice

    Science.gov (United States)

    Lai, Hoang M.; Aronow, Wilbert S.; Mercando, Anthony D.; Kalen, Phoenix; Desai, Harit V.; Gandhi, Kaushang; Sharma, Mala; Amin, Harshad; Lai, Trung M.

    2011-01-01

    Summary Background Statins reduce coronary events in patients with coronary artery disease. Material/Methods Chart reviews were performed in 305 patients (217 men and 88 women, mean age 74 years) not treated with statins during the first year of being seen in an outpatient cardiology practice but subsequently treated with statins. Based on the starting date of statins use, the long-term outcomes of myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft surgery (CABGS) before and after statin use were compared. Results Mean follow-up was 65 months before statins use and 66 months after statins use. MI occurred in 31 of 305 patients (10%) before statins, and in 13 of 305 patients (4%) after statins (pcardiology practice reduces the incidence of MI, PCI, and CABGS. PMID:22129898

  3. Current treatment of dyslipidaemia: PCSK9 inhibitors and statin intolerance.

    Science.gov (United States)

    Koskinas, Konstantinos; Wilhelm, Matthias; Windecker, Stephan

    2016-01-01

    Statins are the cornerstone of the management of dyslipidaemias and prevention of cardiovascular disease. Although statins are, overall, safe and well tolerated, adverse events can occur and constitute an important barrier to maintaining long-term adherence to statin treatment. In patients who cannot tolerate statins, alternative treatments include switch to another statin, intermittent-dosage regimens and non-statin lipid-lowering medications. Nonetheless, a high proportion of statin-intolerant patients are unable to achieve recommended low-density lipoprotein (LDL) cholesterol goals, thereby resulting in substantial residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protease implicated in LDL receptor degradation and plays a central role in cholesterol metabolism. In recent studies, PCSK9 inhibition by means of monoclonal antibodies achieved LDL cholesterol reductions of 50% to 70% across various patient populations and background lipid-lowering therapies, while maintaining a favourable safety profile. The efficacy and safety of the monoclonal antibodies alirocumab and evolocumab were confirmed in statin-intolerant patients, indicating that PCSK9 inhibitors represent an attractive treatment option in this challenging clinical setting. PCSK9 inhibitors recently received regulatory approval for clinical use and may be considered in properly selected patients according to current consensus documents, including patients with statin intolerance. In this review we summarise current evidence regarding diagnostic evaluation of statin-related adverse events, particularly statin-associated muscle symptoms, and we discuss current recommendations on the management of statin-intolerant patients. In view of emerging evidence of the efficacy and safety of PCSK9 inhibitors, we further discuss the role of monoclonal PCSK9 antibodies in the management of statin-intolerant hypercholesterolaemic patients.

  4. NASH Therapy: omega 3 supplementation, vitamin E, insulin sensitizers and statin drugs

    Directory of Open Access Journals (Sweden)

    Stephen Caldwell

    2017-06-01

    Full Text Available Non-alcoholic steatohepatitis (NASH is the more aggressive form of non-alcoholic fatty liver disease (NAFLD. NASH can progress to hepatic fibrosis, cirrhosis, portal hypertension and primary liver cancer. Therapy is evolving with a substantial number of trials of promising new agents now in progress. In this article however, we will examine data for several older forms of therapy which have been fairly extensively studied over the years: Polyunsaturated Fatty Acid (PUFA supplements, vitamin E, insulin sensitizing agents with a focus on pioglitazone and statin agents. Early interest in PUFA derived from their potential benefit in cardio-metabolic disease and the close association of NAFLD/NASH with Metabolic Syndrome. Results have been variable although most studies show reduction of liver fat without other major effects and their effects are influenced by concomitant weight loss and underlying genetic factors. Vitamin E has had some efficacy in pediatric NASH but questionable efficacy in even mild NASH among adults. Pioglitazone has shown significant histological benefit in a number of trials but concern over side-effects (especially weight gain have dampened enthusiasm. A newer insulin sensitizer, liraglutide, has also shown promise in a small randomized, controlled trial. Very limited data exists regarding the histological effects of the statins in NASH and these agents appear to be fairly neutral with neither clear cut benefit nor detriment. Their use is best guided by cardiovascular risks rather than liver histology.

  5. Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia.

    Science.gov (United States)

    Tóth, Štefan; Šajty, Matej; Pekárová, Tímea; Mughees, Adil; Štefanič, Peter; Katz, Matan; Spišáková, Katarína; Pella, Jozef; Pella, Daniel

    2017-07-26

    Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects. In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Zennix fa Pleuran) and omega-3 PUFA 2.52 g+CoQ10 200 mg/day (Pharma Nord ApS) were added, res//. At the end of the 3-month period (±1 week), all patients were evaluated. Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10. The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

  6. Implications of the US Cholesterol Guidelines on Eligibility for Statin Therapy in the Community

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Enserro, Danielle; Larson, Martin G

    2015-01-01

    BACKGROUND: Concerns have been raised that the 2013 atherosclerotic cardiovascular disease (ASCVD) risk estimator overpredicts risk in contemporary cohorts. Whether suboptimal calibration will lead to overtreatment with statins is unknown. We investigated the numbers of people eligible for statin...

  7. Perioperative Statin Therapy Is Not Associated With Reduced Risk of Anastomotic Leakage After Colorectal Resection

    DEFF Research Database (Denmark)

    Bisgård, Anne Sofie; Noack, Morten Westergaard; Klein, Mads

    2013-01-01

    Anastomotic leakage is a serious complication of colorectal surgery. Several studies have demonstrated the beneficial pleiotropic effects of statins, and preliminary studies have suggested that perioperative statin treatment may be associated with reduced risk of anastomotic leakage....

  8. Pharmacogenetics of statin therapy and the endothelial function parameters in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Nadezhda O. Lebedeva

    2016-04-01

    Full Text Available Aim. To investigate the association of variation in lipid-lowering response and endothelial function (EF parameters after atorvastatin therapy in patients with type 2 diabetes mellitus (T2DM with genetic markers of atherosclerosis. Methods. We included 97 patients with T2DM who were prescribed atorvastatin. Fasting lipid profiles and EF parameters were assessed before and after 12 months of statin therapy. For EF evaluation, we performed pulse-wave analysis during reactive hyperaemia. The genotypes for polymorphic markers were identified by real-time polymerase chain reaction with TaqMan probes. The statistical analysis included Wilcoxon, Mann–Whitney and Kruskal–Wallis tests. P-values <0.05 were considered statistically significant. Results. With statin therapy, PPARG2Pro/Pro patients had significantly lower TC and LDL-C levels than PPARG2 Pro/Ala and PPARG2 Ala/Ala patients (TC: 20.74% vs. 4.6% and 5.61%; p = 0.04 and LDL-C: 26.00% vs. 6.11% and 7.32%; p = 0.029. Patients with АРОЕЕ4/Е4 had significantly lower TC and TG levels than other АРОЕ patients (TC: -46.25% for Е4/Е4 vs. +33.33% for Е4/Е2, +5.73% for Е3/Е2, +11.80% for Е3/Е4, -10.92% for Е3/Е3, р = 0,01; TG: -56.52% for Е4/Е4 vs. +24.43% for Е4/Е2, +19.63% for Е3/Е2, +8.05% for Е3/Е4, -20.00% for Е3/Е3, р = 0.04. The patients with GG for TNFα G(238A and GA for TNFα G(308A had significantly greater amplitude of post-occlusive wave increase (Apw than patients with GA for TNFα G(238A and GG for TNFα G(308A (+8.16 % vs. -0.93%, р = 0,04; +44% vs. -4.4%, p = 0.004, respectively. Conclusion. PPARG2Pro12Ala and АРОЕE2/Е3/Е4 polymorphism contributed to the between-patient variability in the response to statin therapy in patients with T2DM. Significant associations of the TNFαgene polymorphism with EF in patients with T2DM suggest an important role of inflammation in the pathogenesis of MVD.

  9. Associations between patients' adherence and GPs' attitudes towards risk, statin therapy and management of non-adherence

    DEFF Research Database (Denmark)

    Barfoed, Benedicte L; Paulsen, Maja S; Christensen, Palle M

    2016-01-01

    BACKGROUND: Previous studies suggest that doctors' personal lifestyle, risk taking personality and beliefs about risk reducing therapies may affect their clinical decision-making. Whether such factors are further associated with patients' adherence with medication is largely unknown. OBJECTIVE...... statin treatment as important, how they managed non-adherence and whether non-adherence annoyed them. The Jackson Personality Inventory-revised was used to measure risk attitude. The GPs' responses were linked to register data on their patients' redeemed statin prescriptions. Mixed effect logistic...

  10. Comparison of different statin therapy to change low-density lipoprotein cholesterol and high-density lipoprotein cholesterol level in Korean patients with and without diabetes.

    Science.gov (United States)

    Khang, Ah Reum; Song, Young Shin; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Jang, Hak Chul; Choi, Sung Hee

    2016-01-01

    It is difficult to apply the proper intensity of statin for new treatment guidelines in clinical settings because of few data about the statin efficacy in Asians. We conducted a retrospective, observational study to estimate the percentage changes in lipid parameters and glucose induced by different statins. We analyzed 3854 patients including those with nondiabetes and diabetes treated at the outpatient clinic between 2003 and 2013 who were statin-naïve and maintained fixed-dose of statin for at least 18 months. Moderate- and low-intensity statin therapy was effective in reducing low-density lipoprotein cholesterol (LDL-C) to statin group. The effects of statins in elevating high-density lipoprotein cholesterol were similar in each statin groups, except the ezetimibe-simvastatin group (4.5 ± 2.1%) and high-dose atorvastatin groups (9.7 ± 3.3% and 8.7 ± 2.4% for 40 mg and 80 mg of atorvastatin/day, respectively). High-density lipoprotein cholesterol increased less and LDL-C decreased more in diabetes than in nondiabetes. There were no significant changes of fasting glucose after statin use in nondiabetic patients. Moderate- or low-intensity statin was effective enough in reaching National Cholesterol Education Program Adult Treatment Panel III LDL-C target goals in Koreans. Low-intensity statin showed around 30% LDL-C reduction from the baseline level in Koreans, which is comparable to moderate-intensity statin in new guideline. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  11. Statin therapy reduces the likelihood of suboptimal blood pressure control among Ugandan adult diabetic patients

    Directory of Open Access Journals (Sweden)

    Lumu W

    2017-02-01

    Full Text Available William Lumu,1 Leaticia Kampiire,2 George Patrick Akabwai,3 Daniel Ssekikubo Kiggundu,4 Davis Kibirige5 1Department of Medicine and Diabetes/Endocrine Unit, Mengo Hospital, 2Infectious Disease Research Collaboration, 3Baylor College of Medicine Children’s Foundation, 4Nephrology Unit, Mulago National Referral and Teaching Hospital, 5Department of Medicine, Uganda Martyrs Hospital Lubaga, Kampala, Uganda Background: Hypertension is one of the recognized risk factors of cardiovascular diseases in adult diabetic patients. High prevalence of suboptimal blood pressure (BP control has been well documented in the majority of studies assessing BP control in diabetic patients in sub-Saharan Africa. In Uganda, there is a dearth of similar studies. This study evaluated the prevalence and correlates of suboptimal BP control in an adult diabetic population in Uganda.Patients and methods: This was a cross-sectional study that enrolled 425 eligible ambulatory adult diabetic patients attending three urban diabetic outpatient clinics over 11 months. Data about their sociodemographic characteristics and clinical history were collected using pre-tested questionnaires. Suboptimal BP control was defined according to the 2015 American Diabetes Association standards of diabetes care guideline as BP levels ≥140/90 mmHg.Results: The mean age of the study participants was 52.2±14.4 years, with the majority being females (283, 66.9%. Suboptimal BP control was documented in 192 (45.3% study participants and was independently associated with the study site (private hospitals; odds ratio 2.01, 95% confidence interval 1.18–3.43, P=0.01 and use of statin therapy (odds ratio 0.5, 95% confidence interval 0.26–0.96, P=0.037.Conclusion: Suboptimal BP control was highly prevalent in this study population. Strategies to improve optimal BP control, especially in the private hospitals, and the use of statin therapy should be encouraged in adult diabetic patients

  12. High-dose statin therapy in patients with stable coronary artery disease: treating the right patients based on individualized prediction of treatment effect

    NARCIS (Netherlands)

    Dorresteijn, Johannes A. N.; Boekholdt, S. Matthijs; van der Graaf, Yolanda; Kastelein, John J. P.; LaRosa, John C.; Pedersen, Terje R.; Demicco, David A.; Ridker, Paul M.; Cook, Nancy R.; Visseren, Frank L. J.

    2013-01-01

    Clinicians need to identify coronary artery disease patients for whom the benefits of high-dose versus usual-dose statin therapy outweigh potential harm. We therefore aimed to develop and validate a model for prediction of the incremental treatment effect of high-dose statins for individual patients

  13. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

    NARCIS (Netherlands)

    Stroes, Erik S.; Thompson, Paul D.; Corsini, Alberto; Vladutiu, Georgirene D.; Raal, Frederick J.; Ray, Kausik K.; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G.; Bruckert, Eric; de Backer, Guy; Krauss, Ronald M.; Laufs, Ulrich; Santos, Raul D.; Hegele, Robert A.; Hovingh, G. Kees; Leiter, Lawrence A.; Mach, Francois; März, Winfried; Newman, Connie B.; Wiklund, Olov; Jacobson, Terry A.; Catapano, Alberico L.; Chapman, M. John; Ginsberg, Henry N.; Leiter, Lawrence

    2015-01-01

    Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of

  14. Childhood adversity as a predictor of non-adherence to statin therapy in adulthood.

    Directory of Open Access Journals (Sweden)

    Maarit Jaana Korhonen

    Full Text Available To investigate whether adverse experiences in childhood predict non-adherence to statin therapy in adulthood.A cohort of 1378 women and 538 men who initiated statin therapy during 2008-2010 after responding to a survey on childhood adversities, was followed for non-adherence during the first treatment year. Log-binomial regression was used to estimate predictors of non-adherence, defined as the proportion of days covered by dispensed statin tablets <80%. In fully adjusted models including age, education, marital status, current smoking, heavy alcohol use, physical inactivity, obesity, presence of depression and cardiovascular comorbidity, the number of women ranged from 1172 to 1299 and that of men from 473 to 516, because of missing data on specific adversities and covariates.Two in three respondents reported at least one of the following six adversities in the family: divorce/separation of the parents, long-term financial difficulties, severe conflicts, frequent fear, severe illness, or alcohol problem of a family member. 51% of women and 44% of men were non-adherent. In men, the number of childhood adversities predicted an increased risk of non-adherence (risk ratio [RR] per adversity 1.11, 95% confidence interval [CI] 1.01-1.21], P for linear trend 0.013. Compared with those reporting no adversities, men reporting 3-6 adversities had a 1.44-fold risk of non-adherence (95% CI 1.12-1.85. Experiencing severe conflicts in the family (RR 1.27, 95% CI 1.03-1.57] and frequent fear of a family member (RR 1.27, 95% CI 1.00-1.62] in particular, predicted an increased risk of non-adherence. In women, neither the number of adversities nor any specific type of adversity predicted non-adherence.Exposure to childhood adversity may predict non-adherence to preventive cardiovascular medication in men. Usefulness of information on childhood adversities in identification of adults at high risk of non-adherence deserves further research.

  15. No modifying effect of nutritional status on statins therapy in relation to all-cause death in older patients with coronary artery disease.

    Science.gov (United States)

    Huang, Bao-Tao; Huang, Fang-Yang; Pu, Xiao-Bo; Xia, Tian-Li; Peng, Yong; Chen, Fei; Yang, Yong; Liao, Yan-Biao; Chen, Mao

    2017-12-19

    Statins therapy in the secondary prevention of coronary artery disease (CAD) is associated with a lower risk of adverse cardiovascular events. However, little is known regarding the association of elderly patients with nutritional risk on statin therapy. To investigate whether older patients with CAD who were at nutritional risk gain similar survival benefit from statins therapy as their counterparts without nutritional risk. We conducted a retrospective hospital-based cohort study among 1705 patients with CAD who were older than 65 years of age, using coronary heart disease database from 2008 to 2012. Nutritional status of included patients was gauged using the geriatric nutritional risk index. After stratification by nutritional status, the hazard of all-cause death was compared between those with or without statins therapy. Of the 1705 patients included in the study (mean age 72 years; 73% male), all-cause death occurred in 146 (9.2%) patients with statins use and in 33 (26.2%) patients without statins use. The rate of all-cause death was higher in patients not receiving statins irrespective of nutritional status. After adjustments for potential confounders, the HR with statins use was 0.33 (95% CI 0.20-0.55) in patients without nutritional risk and 0.47 (95% CI 0.22-1.00) in patients with nutritional risk. No interaction effect was detected between nutritional status and statins use in relation to all-cause death (P value for interaction effect 0.516). Despite of the patient's nutritional status, statins therapy as a secondary prevention in elderly CAD patients was associated with decreased risk of all-cause death.

  16. [Use of pharmacogenetic testing to prevent adverse drug reactions during statin therapy].

    Science.gov (United States)

    Rumyantsev, N A; Kukes, V G; Kazakov, R E; Rumyantsev, A A; Sychev, D A

    The number of patients receiving statins increases every year and due to the fact that they should take statins during their lives, the problem of their safety use comes to the forefront. The paper analyzes the safety of using the medications of this group and discusses the diagnosis of myopathies induced by statins and the occurrence of immune-mediated statin myopathies. It considers a personalized approach to prescribing statins, analyzes Russian and foreign experience in using pharmacogenetics to reduce the risk of myopathies, publishes the results of the authors' experience in clinically introducing pharmacogenetic testing at hospitals, and analyzes the long-term results of determining the polymorphism of the SLCO1B1 gene for the prediction of the risk of adverse events when using statins and estimating patient compliance to prescribed treatment.

  17. 'Muscle-sparing' statins: preclinical profiles and future clinical use.

    Science.gov (United States)

    Pfefferkorn, Jeffrey A

    2009-03-01

    Coronary heart disease (CHD) is a leading cause of death in the US, and hypercholesterolemia is a key risk factor for this disease. The current standard of care for treating hypercholesterolemia is the use of HMG-CoA reductase inhibitors, also known as statins, which block the rate-limiting step of cholesterol biosynthesis. In widespread clinical use, statins have proven safe and effective for both primary prevention of CHD and secondary prevention of coronary events. Results from several recent clinical trials have demonstrated that increasingly aggressive cholesterol-lowering therapy might offer additional protection against CHD compared with less aggressive treatment standards. While higher doses of current statin therapies are capable of achieving these more aggressive treatment goals, in certain cases statin-induced myalgia, the muscle pain or weakness that sometimes accompanies high-dose statin therapy, limits patient compliance with a treatment regimen. To address this limitation, efforts have been undertaken to develop highly hepatoselective statins that are capable of delivering best-in-class efficacy with minimized risk of dose-limiting myalgia. In this review, the preclinical and early clinical data for these next generation statins are discussed.

  18. The importance of age and statin therapy in the interpretation of Lp-PLA(2) in ACS patients, and relation to CRP.

    Science.gov (United States)

    Franeková, J; Kettner, J; Kubíček, Z; Jabor, A

    2015-01-01

    C-reactive protein (CRP) is a marker of arterial inflammation while lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is related to plaque instability. The aim of this study was to evaluate the correlation between the risk of unstable plaque presenting as acute coronary syndrome (ACS) and Lp-PLA(2), and to assess the influence of statins on interpretation of Lp-PLA(2). A total of 362 consecutive patients presenting to the emergency department (ED) with acute chest pain suggestive of ACS were evaluated by cardiologists as STEMI, NSTEMI, or unstable angina, and non-ACS. Serum biomarkers measured on admission: troponin I, C-reactive protein (Abbott), and Lp-PLA(2) (DiaDexus). Four groups were defined according to the final diagnosis and history of statin medication: ACS/statin-; ACS/statin+; non-ACS/statin-; non-ACS/statin+. Lp-PLA(2) was highest in ACS/statin- group; statins decreased Lp-PLA(2) both in ACS and non-ACS of about 20 %. Lp-PLA(2) was higher in ACS patients in comparison with non-ACS patients group without respect to statin therapy (pPLA(2) predicted worse outcome (in terms of acute coronary syndrome) effectively in patients up to 62 years; limited prediction was found in older patients. C-reactive protein (CRP) failed to discriminate four groups of patients. Statin therapy and age should be taken into consideration while interpreting Lp-PLA(2) concentrations and lower cut-off values should be used for statin-treated persons.

  19. The effect of adherence to statin therapy on cardiovascular mortality: quantification of unmeasured bias using falsification end-points

    Directory of Open Access Journals (Sweden)

    Maarten J. Bijlsma

    2016-04-01

    Full Text Available Abstract Background To determine the clinical effectiveness of statins on cardiovascular mortality in practice, observational studies are needed. Control for confounding is essential in any observational study. Falsification end-points may be useful to determine if bias is present after adjustment has taken place. Methods We followed starters on statin therapy in the Netherlands aged 46 to 100 years over the period 1996 to 2012, from initiation of statin therapy until cardiovascular mortality or censoring. Within this group (n = 49,688, up to 16 years of follow-up, we estimated the effect of adherence to statin therapy (0 = completely non-adherent, 1 = fully adherent on ischemic heart diseases and cerebrovascular disease (ICD10-codes I20-I25 and I60-I69 as well as respiratory and endocrine disease mortality (ICD10-codes J00-J99 and E00-E90 as falsification end points, controlling for demographic factors, socio-economic factors, birth cohort, adherence to other cardiovascular medications, and diabetes using time-varying Cox regression models. Results Falsification end-points indicated that a simpler model was less biased than a model with more controls. Adherence to statins appeared to be protective against cardiovascular mortality (HR: 0.70, 95 % CI 0.61 to 0.81. Conclusions Falsification end-points helped detect overadjustment bias or bias due to competing risks, and thereby proved to be a useful technique in such a complex setting.

  20. Patient adherence to generic versus brand statin therapy after acute myocardial infarction: Insights from the Can Rapid Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines Registry.

    Science.gov (United States)

    O'Brien, Emily C; McCoy, Lisa A; Thomas, Laine; Peterson, Eric D; Wang, Tracy Y

    2015-07-01

    Statins reduce mortality after acute myocardial infarction, but up to half of patients discontinue statin use within 1 year of therapy initiation. Although cost may influence medication adherence, it is unknown whether use of generic versus brand statins influences adherence. We linked detailed inhospital clinical data for 1421 non-ST-segment elevation myocardial infarction patients discharged on a statin in 2006 to Medicare Part D medication claims records to examine postdischarge medication use. One-year statin adherence was defined using the proportion of days covered with optimal adherence ≥80%. We examined the association of brand versus generic statin prescription and 1-year adherence after adjusting for demographics, clinical factors, predischarge lipid values, prior statin use, and socioeconomic status. Overall, 65.5% of statin fills were for brand-name statins. There were few baseline differences in demographics and clinical factors among generic versus brand users. Patient copay amounts were higher for brand versus generic statins (median = $25 vs $5, P brand statins (55.9%; P = .93). Statin adherence rates remained similar between generic and brand users after adjusting for demographics, clinical risk factors, lipid value, prior statin use, and socioeconomic status. In a cohort of older non-ST-segment elevation myocardial infarction patients, we found no evidence that use of generic versus brand drug was associated with higher adherence to statins at 1 year after hospital discharge. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Well Connected, a platform for safe online communication and therapy

    NARCIS (Netherlands)

    Postel, Marloes Gerda; van Regteren, B.J.

    2012-01-01

    Well Connected, a platform for safe online communication and therapy Introduction Well Connected is a flexible, safe and user friendly e-health platform with a wide range of applications. Over the last 7 years 5000 patients were treated or a variety of addiction related problems. Besides creating an

  2. The Risk of Hepatotoxicity, New Onset Diabetes and Rhabdomyolysis in the Era of High-Intensity Statin Therapy: Does Statin Type Matter?

    Science.gov (United States)

    Benes, Lane B; Bassi, Nikhil S; Davidson, Michael H

    The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management have placed greater emphasis on high-intensity statin dosing for those with known cardiovascular disease or diabetes mellitus. Differences in risk of hepatotoxicity, new onset diabetes and rhabdomyolysis specifically between the high-intensity statins and the most common moderate-intensity statin, simvastatin, were not found to a significant degree in this review. Rather, baseline characteristics and drug-drug interactions (DDIs) appear to be more important regarding the risk of these adverse effects. Pharmacogenetic differences in statin metabolism may explain individual susceptibility, however genetic testing is not felt to be cost effective at this time. More importantly, statin choice should consider concomitant use of the many prevalent CYP3A4 inhibitors or inducers, and when present, rosuvastatin selection is recommended to reduce DDIs and risk of statin-induced adverse effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Is electroconvulsive therapy during pregnancy safe?

    Science.gov (United States)

    Jiménez-Cornejo, Magdalena; Zamorano-Levi, Natalia; Jeria, Álvaro

    2016-12-07

    Therapeutic options for psychiatric conditions are limited during pregnancy because many drugs are restricted or contraindicated. Electroconvulsive therapy constitutes an alternative, however there is controversy over its safety. Using the Epistemonikos database, which is maintained by searching multiple databases, we found five systematic reviews, including 81 studies overall describing case series or individual cases. Data were extracted from the identified reviews and summary tables of the results were prepared using the GRADE method. We concluded it is not clear what are the risks associated with electroconvulsive therapy during pregnancy because the certainty of the existing evidence is very low. Likewise, existing systematic reviews and international clinical guidelines differ in their conclusions and recommendations.

  4. Impact of educational outreach intervention on enhancing health care providers' knowledge about statin therapy prescribing in Malaysian patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Elnaem, Mohamed Hassan; Nik Mohamed, Mohamad Haniki; Zaman Huri, Hasniza; Azarisman, Shah M

    2018-03-06

    Previous research reported underutilization of statin therapy among patients with type 2 diabetes mellitus. Improving health care providers' awareness and understanding of the benefits and risks of statin treatment could be of assistance in optimizing the statin prescribing process. This study aimed to assess health care providers' knowledge related to statin therapy and the impact of educational outreach intervention based on the perceived knowledge. This was a cross-sectional study based on educational outreach intervention targeting physicians and pharmacists in 1 major tertiary hospital in the state of Pahang, Malaysia. Participants responded to a 12-item, validated questionnaire both prior to and after the outreach educational program. Two sessions were conducted separately for 2 cohorts of pharmacists and physicians. The knowledge scores prior to and after the educational intervention were calculated and compared using a paired-samples t-test. The response rate to both pre-and post-educational outreach questionnaires was 91% (40/44). Prior to the intervention, around 84% (n37) of the participants decided to initiate statin therapy for both pre-assessment clinical case scenarios; however, only 27% (n12) could state the clinical benefits of statin therapy. Forty-five percent (n20) could state the drug to drug interactions, and 52.3% (n23) could identify the statin therapy that can be given at any time day/evening. The educational outreach program increased participants' knowledge scores of 1.450 (95% CI, 0.918 to 1.982) point, P health care providers' knowledge and beliefs about statin therapy. This type of intervention is considered effective for short-term knowledge enhancement. Further research is needed to test the long-term efficacy of such intervention. © 2018 John Wiley & Sons, Ltd.

  5. Benefits & risks of statin therapy for primary prevention of cardiovascular disease in Asian Indians – A population with the highest risk of premature coronary artery disease & diabetes

    Science.gov (United States)

    Enas, Enas A.; Kuruvila, Arun; Khanna, Pravien; Pitchumoni, C.S.; Mohan, Viswanathan

    2013-01-01

    Several reviews and meta-analyses have demonstrated the incontrovertible benefits of statin therapy in patients with cardiovascular disease (CVD). But the role for statins in primary prevention remained unclear. The updated 2013 Cochrane review has put to rest all lingering doubts about the overwhelming benefits of long-term statin therapy in primary prevention by conclusively demonstrating highly significant reductions in all-cause mortality, major adverse cardiovascular events (MACE) and the need for coronary artery revascularization procedures (CARPs). More importantly, these benefits of statin therapy are similar at all levels of CVD risk, including subjects at low (statins is also highly effective in delaying and avoiding expensive CARPs such as angioplasties, stents, and bypass surgeries. There is no evidence of any serious harm or threat to life caused by statin therapy, though several adverse effects that affect the quality of life, especially diabetes mellitus (DM) have been reported. Asian Indians have the highest risk of premature coronary artery disease (CAD) and diabetes. When compared with Whites, Asian Indians have double the risk of CAD and triple the risk of DM, when adjusted for traditional risk factors for these diseases. Available evidence supports the use of statin therapy for primary prevention in Asian Indians at a younger age and with lower targets for low-density lipoprotein cholesterol (LDL-C) and non-high density lipoprotein (non-HDL-C), than those currently recommended for Americans and Europeans. Early and aggressive statin therapy offers the greatest potential for reducing the continuing epidemic of CAD among Indians. PMID:24434254

  6. Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

    Directory of Open Access Journals (Sweden)

    Pyoung Ahn

    2013-12-01

    Full Text Available Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that statin-induced muscle injury was aggravated by hypothyroidism resulting in her full-blown rhabdomyolysis. Although this patient was successfully treated with continuous venovenous hemofiltration and L-thyroxin replacement, rhabdomyolysis with acute kidney injury is a potentially life-threatening disorder. Physicians must pay special attention to the possible presence of subclinical hypothyroidism when administering statins in patients with hypercholesterolemia.

  7. Rhabdomyolysis and Acute Kidney Injury Associated with Hypothyroidism and Statin Therapy

    OpenAIRE

    Ahn, Pyoung; Min, Hyun-Jun; Park, Sang-Hyun; Lee, Byoung-Mu; Choi, Myung-Jin; Yoon, Jong-Woo; Koo, Ja-Ryong

    2013-01-01

    Rhabdomyolysis is a syndrome involving the breakdown of skeletal muscle that causes myoglobin and other intracellular proteins to leak into the circulatory system, resulting in organ injury including acute kidney injury. We report a case of statin-induced rhabdomyolysis and acute kidney injury that developed in a 63-year-old woman with previously undiagnosed hypothyroidism. Untreated hypothyroidism may have caused her hypercholesterolemia requiring statin treatment, and it is postulated that ...

  8. Safety of statins.

    Science.gov (United States)

    Brown, William Virgil

    2008-12-01

    To examine the evidence for the adverse effects that have been reported during the use of statins. We now have over twenty years of prescription use and many large well controlled trials with statin therapy for hypercholesterolemia. There is only one significant and well documented adverse effect with this group of drugs, rhabdomyolysis. Significant muscle damage is very rare when statin therapy is used in patients carefully screened for concomitant use of other drugs which may interfere with statin catabolism and excretion. Patients with severely impaired liver function are also at risk due to the importance of hepatic excretion of all statins. Chronic myalgias or other pain syndromes have not been confirmed by blinded placebo controlled trials. A significant and reproducible rise in liver enzymes (alanine and aspartate aminotransferases) is observed in 1 to 3% of patients but actual liver damage may not occur at all. Benign and transient proteinuria occurs without evidence of altered renal function. Creatinine clearance is usually increased by statins. Peripheral neuropathy may be a rare adverse effect and this needs further study. Statins are very effective at reducing the incidence of myocardial infarction, stroke and other manifestations of vascular disease. The adverse event rates are very uncommon and the benefit risk ratio is extremely high.

  9. Statin-related myotoxicity.

    Science.gov (United States)

    Fernandes, Vera; Santos, Maria Joana; Pérez, Antonio

    2016-05-01

    Statin therapy has a very important role in decreasing cardiovascular risk, and treatment non-compliance may therefore be a concern in high cardiovascular risk patients. Myotoxicity is a frequent side effect of statin therapy and one of the main causes of statin discontinuation, which limits effective treatment of patients at risk of or with cardiovascular disease. Because of the high proportion of patients on statin treatment and the frequency of statin-related myotoxicity, this is a subject of concern in clinical practice. However, statin-related myotoxicity is probably underestimated because there is not a gold standard definition, and its diagnosis is challenging. Moreover, information about pathophysiology and optimal therapeutic options is scarce. Therefore, this paper reviews the knowledge about the definition, pathophysiology and predisposing conditions, diagnosis and management of statin-related myotoxicity, and provides a practical scheme for its management in clinical practice. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  10. The effect of statin therapy on oxidative stress indices in patients with arterial hypertension and type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    V. D. Nemtsova

    2018-02-01

    Full Text Available Objective: to study the effect of statin therapy on the oxidative and antioxidant systems parameters in patients with arterial hypertension (AH and concomitant type 2 diabetes mellitus (DM2T. Materials and methods. 126 patients (55 males and 71 females, average age was 57.8 ± 6.2 years with AH stage II and compensated DM2T were divided into 2 groups: the 1 group – with AH and DM2T (n = 69, who were constantly taking statins (rosuvastatin 10 mg/day or atorvastatin 20 mg/day for at least 1 year; the 2 group – patients with AH and DM2T (n = 57 who did not take statins. The control group included 20 healthy volunteers. The parameters of lipid and carbohydrate metabolism, the degree of insulin resistance (HOMA-IR, the state of the oxidant system (malonic dialdehyde level –MDA, the antioxidant system (the activity of glutathione peroxidase (GPO and the level of sulfhydryl groups -SH-groups were evaluated. The statistics was carried out using the Statistica software package, version 8.0. Results. In the 1st group only the levels of LDL cholesterol significantly differed from the control group (P 0.05. In the 1st group in comparison with the 2nd group unreliable increase in GPO and SH-groups levels on the background of the increase in MDA levels (P > 0.05 were observed. Conclusions. The use of statins in low doses in AH combined with DM2T was accompanied by a nonsignificant improvement of antioxidant protection parameters on the background of increased insulin resistance and increased activity of lipid peroxidation.

  11. Therapeutic implication of coenzyme Q10 during statin therapy: pros and cons

    Directory of Open Access Journals (Sweden)

    Mir-Jamal Hosseini

    2015-09-01

    Full Text Available Coenzyme Q10 (CoQ10 is a vitamin-like substance, and a natural intermediate of electron transport chain (ETC of mitochondria which can accepts and donates electrons from complex I and complex II. CoQ10 shares a biosynthetic pathway with cholesterol and dolichol thus it can be a potential target of the widely available lipid-lowering drugs. The lipid lowering drugs such as statins, are widely administered to individuals who have high cholesterol levels. This article reviews the a clinical benefits of CoQ10 b association between administration of statin and CoQ10 deficiency and c involvement of CoQ10 in statin-associated myopathy.

  12. The impact of pharmacist face-to-face counseling to improve medication adherence among patients initiating statin therapy

    Directory of Open Access Journals (Sweden)

    Duncan I

    2012-04-01

    Full Text Available Michael Taitel1, Jenny Jiang1, Kristi Rudkin2, Susan Ewing2, Ian Duncan 1Clinical Outcomes and Analytics, Walgreens, 2Corporate Innovation Team, Walgreens, Deerfield, Illinois, USAPurpose: To evaluate the impact of a community-based pharmacist-led face-to-face counseling program on medication adherence for patients who were new to therapy (NTT for statin medications.Patients and methods: This retrospective cohort study evaluated a program that was implemented in 76 national community pharmacies located in the midwest USA. It consisted of two face-to-face patient counseling sessions with a pharmacist that addressed patient barriers to adherence. A group of 2056 NTT statin patients was identified between September 1, 2010 and October 31, 2010, and was followed for 12 months. The intervention group consisted of 586 patients, and the comparison group comprised 516 patients. Outcomes were measured using the continuous medication possession ratio (MPR, categorical MPR, and medication persistency.Results: After adjusting for covariates, the intervention group had statistically greater MPR than the comparison group at every month measured. For example, at 12 months the intervention group had a MPR of 61.8% (CI, 54.5%–69.2% and the comparison group had a MPR of 56.9% (CI, 49.5%–64.3%; this 4.9% difference is significant (P < 0.01. The 12 month categorical MPR also showed significant differences between groups (χ2 = 6.12, P < 0.05; 40.9% of the intervention group and 33.7% of comparison group had a MPR greater than or equal to 80%. Finally, the intervention group had significantly greater persistency with their medication therapy than the comparison group at 60, 90, 120, and 365 days.Conclusion: Patients who participated in brief face-to-face counseling sessions with a community pharmacist at the beginning of statin therapy demonstrated greater medication adherence and persistency than a comparison group. This brief targeted intervention at the

  13. Utility of Nontraditional Risk Markers in Individuals Ineligible for Statin Therapy According to the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines.

    Science.gov (United States)

    Yeboah, Joseph; Polonsky, Tamar S; Young, Rebekah; McClelland, Robyn L; Delaney, Joseph C; Dawood, Farah; Blaha, Michael J; Miedema, Michael D; Sibley, Christopher T; Carr, J Jeffrey; Burke, Gregory L; Goff, David C; Psaty, Bruce M; Greenland, Philip; Herrington, David M

    2015-09-08

    In the general population, the majority of cardiovascular events occur in people at the low to moderate end of population risk distribution. The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol recommends consideration of statin therapy for adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% based on traditional risk factors. Whether use of nontraditional risk markers can improve risk assessment in those below this threshold for statin therapy is unclear. Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population sample free of clinical CVD at baseline, we calibrated the Pooled Cohort Equations (cPCE). ASCVD was defined as myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke. Adults with an initial cPCE statin eligible: low-density lipoprotein cholesterol ≥160 mg/dL; family history of ASCVD; high-sensitivity C-reactive protein ≥2 mg/dL; coronary artery calcium score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity; and ankle-brachial index statin eligible. Of 5185 participants not taking statins with complete data (age, 45-84 years), 4185 had a cPCE risk statin eligible) by at least 1 of the additional risk marker criteria. In this generally low-risk population sample, a large proportion of ASCVD events occurred among adults with a 10-year cPCE risk 7.5% who may warrant statin therapy considerations. © 2015 American Heart Association, Inc.

  14. Primary Prevention With Statins

    DEFF Research Database (Denmark)

    Mortensen, Martin B; Afzal, Shoaib; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: Guidelines recommend initiating primary prevention for atherosclerotic cardiovascular disease (ASCVD) with statins based on absolute ASCVD risk assessment. Recently, alternative trial-based and hybrid approaches were suggested for statin treatment eligibility. OBJECTIVES: This study...... the population studied, 42% were eligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) risk assessment and cholesterol treatment guidelines approach, versus 56% with the trial-based approach and 21% with the hybrid approach. Among these statin......-eligible subjects, the ASCVD event rate per 1,000 person-years was 9.8, 6.8, and 11.2, respectively. The ACC/AHA-recommended absolute risk score was well calibrated around the 7.5% 10-year ASCVD risk treatment threshold and discriminated better than the trial-based or hybrid approaches. Compared with the ACC...

  15. Statin-Associated Side Effects.

    Science.gov (United States)

    Thompson, Paul D; Panza, Gregory; Zaleski, Amanda; Taylor, Beth

    2016-05-24

    Hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors or statins are well tolerated, but associated with various statin-associated symptoms (SAS), including statin-associated muscle symptoms (SAMS), diabetes mellitus (DM), and central nervous system complaints. These are "statin-associated symptoms" because they are rare in clinical trials, making their causative relationship to statins unclear. SAS are, nevertheless, important because they prompt dose reduction or discontinuation of these life-saving mediations. SAMS is the most frequent SAS, and mild myalgia may affect 5% to 10% of statin users. Clinically important muscle symptoms, including rhabdomyolysis and statin-induced necrotizing autoimmune myopathy (SINAM), are rare. Antibodies against HMG-CoA reductase apparently provoke SINAM. Good evidence links statins to DM, but evidence linking statins to other SAS is largely anecdotal. Management of SAS requires making the possible diagnosis, altering or discontinuing the statin treatment, and using alternative lipid-lowering therapy. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. Polygenic Risk Score Identifies Subgroup With Higher Burden of Atherosclerosis and Greater Relative Benefit From Statin Therapy in the Primary Prevention Setting.

    Science.gov (United States)

    Natarajan, Pradeep; Young, Robin; Stitziel, Nathan O; Padmanabhan, Sandosh; Baber, Usman; Mehran, Roxana; Sartori, Samantha; Fuster, Valentin; Reilly, Dermot F; Butterworth, Adam; Rader, Daniel J; Ford, Ian; Sattar, Naveed; Kathiresan, Sekar

    2017-05-30

    Relative risk reduction with statin therapy has been consistent across nearly all subgroups studied to date. However, in analyses of 2 randomized controlled primary prevention trials (ASCOT [Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm] and JUPITER [Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin]), statin therapy led to a greater relative risk reduction among a subgroup at high genetic risk. Here, we aimed to confirm this observation in a third primary prevention randomized controlled trial. In addition, we assessed whether those at high genetic risk had a greater burden of subclinical coronary atherosclerosis. We studied participants from a randomized controlled trial of primary prevention with statin therapy (WOSCOPS [West of Scotland Coronary Prevention Study]; n=4910) and 2 observational cohort studies (CARDIA [Coronary Artery Risk Development in Young Adults] and BioImage; n=1154 and 4392, respectively). For each participant, we calculated a polygenic risk score derived from up to 57 common DNA sequence variants previously associated with coronary heart disease. We compared the relative efficacy of statin therapy in those at high genetic risk (top quintile of polygenic risk score) versus all others (WOSCOPS), as well as the association between the polygenic risk score and coronary artery calcification (CARDIA) and carotid artery plaque burden (BioImage). Among WOSCOPS trial participants at high genetic risk, statin therapy was associated with a relative risk reduction of 44% (95% confidence interval [CI], 22-60; P statin therapy was 3.6% (95% CI, 2.0-5.1) among those in the high genetic risk group and 1.3% (95% CI, 0.6-1.9) in all others. Each 1-SD increase in the polygenic risk score was associated with 1.32-fold (95% CI, 1.04-1.68) greater likelihood of having coronary artery calcification and 9.7% higher (95% CI, 2.2-17.8) burden of carotid plaque. Those at high genetic risk have a greater

  17. STATINS AND MYOPATHY: MOLECULAR MECHANISMS

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2012-01-01

    Full Text Available The safety of statin therapy is considered. In particular the reasons of a complication such as myopathy are discussed in detail. The molecular mechanisms of statin myopathy , as well as its risk factors are presented. The role of coenzyme Q10 in the myopathy development and coenzyme Q10 application for the prevention of this complication are considered. 

  18. Beyond statin therapy: a review of the management of residual risk in diabetes mellitus.

    LENUS (Irish Health Repository)

    Judge, Eoin P

    2010-09-01

    Total cholesterol and low-density lipoprotein (LDL) cholesterol exhibit an independent, strong, continuous correlation with cardiovascular events. The effectiveness of hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in the treatment and prevention of atherosclerosis is well-established. However, despite the lowering of LDL targets and the increased use of statins, patients with type 2 diabetes mellitus (DM) continue to experience a higher proportion of adverse coronary artery disease events. This is as a result of an atherogenic dyslipidaemia, characterized by low levels of high-density lipoprotein and elevated plasma triglyceride concentrations, often with high levels of cholesterol-rich remnant particles. This article will review dyslipidaemia and its role in DM, and will discuss available treatment modalities that address residual cardiovascular risk in this disease.

  19. Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

    Science.gov (United States)

    Kim, Jin Sug; Kim, Weon; Park, Ji Yoon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyun; Moon, Ju-Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

    2017-01-01

    Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction

  20. On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy

    DEFF Research Database (Denmark)

    Mora, Samia; Glynn, Robert J; Boekholdt, S Matthijs

    2012-01-01

    The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), tri...

  1. Impact of statin therapy on coronary plaque composition: A systematic review and meta-analysis of virtual histology intravascular ultrasound studies

    NARCIS (Netherlands)

    M. Banach (Maciej); C. Serban (Corina); A. Sahebkar (Amirhossein); D.P. Mikhailidis (Dimitri P.); S. Ursoniu (Sorin); K.K. Ray (Kausik K.); J. Rysz (Jacek); P.P. Toth (Peter); P. Muntner (Paul); S. Mosteoru (Svetlana); H.M. Garcia-Garcia (Hector); G.K. Hovingh (Kees); J.J.P. Kastelein (John); P.W.J.C. Serruys (Patrick)

    2015-01-01

    textabstractBackground: Virtual histology intravascular ultrasound (VH-IVUS) imaging is an innovative tool for the morphological evaluation of coronary atherosclerosis. Evidence for the effects of statin therapy on VH-IVUS parameters have been inconclusive. Consequently, we performed a systematic

  2. Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies

    NARCIS (Netherlands)

    Banach, Maciej; Serban, Corina; Sahebkar, Amirhossein; Mikhailidis, Dimitri P.; Ursoniu, Sorin; Ray, Kausik K.; Rysz, Jacek; Toth, Peter P.; Muntner, Paul; Mosteoru, Svetlana; García-García, Hector M.; Hovingh, G. Kees; Kastelein, John J. P.; Serruys, Patrick W.

    2015-01-01

    Virtual histology intravascular ultrasound (VH-IVUS) imaging is an innovative tool for the morphological evaluation of coronary atherosclerosis. Evidence for the effects of statin therapy on VH-IVUS parameters have been inconclusive. Consequently, we performed a systematic review and meta-analysis

  3. Online Learning of Safe Patient Transfers in Occupational Therapy Education

    Directory of Open Access Journals (Sweden)

    Cynthia L. Hayden D. H. Ed., OTR/L, CHT

    2013-02-01

    Full Text Available Online higher education is steadily increasing. For programs in allied health to be offered effectively in an elearning format, clinical psychomotor skills need to be addressed. The aim of this research was to design, implement, and evaluate an online safe patient transfers module for occupational therapy assistant (OTAstudents. The efficacy of teaching safe patient transfers in an e-learning environment was appraised using both quantitative and qualitative analysis. The applied research project was completed at a Tennessee community college. A convenience sample of eighteen students participated in the pilot study. Twenty-five studentsparticipated in the subsequent study. The instructional design of the course was based on Mager’s CriterionReferenced Instruction model. Streaming video was used as the delivery method for course material. A pretest/posttest evaluated the students’ cognitive knowledge of safe patient transfers. A behavioral transferscompetency checklist was used to rate videotapes of students’ performance of assisted stand pivot and dependent sliding board transfers. Research findings indicated students were able to learn this psychomotor clinical skill online with beginning proficiency. A paired t-test showed marked improvement of cognitive knowledge. A student learning survey revealed the majority of students preferred at least one hands-on classroom session where instructor feedback and interaction with classmates confirmed safe and effectiveclinical technique.

  4. Baseline characteristics of participants in the JUPITER trial, a randomized placebo-controlled primary prevention trial of statin therapy among individuals with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein

    NARCIS (Netherlands)

    Ridker, Paul M.; Fonseca, Francisco A. H.; Genest, Jacques; Gotto, Antonio M.; Kastelein, John J. P.; Khurmi, Nardev S.; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J.; Nordestgaard, Borge G.; Shepherd, James; Willerson, James T.; Glynn, Robert J.

    2007-01-01

    The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a randomized, double-blind, placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein (LDL) cholesterol

  5. Eligibility for statin therapy by the JUPITER trial criteria and subsequent mortality.

    Science.gov (United States)

    Cushman, Mary; McClure, Leslie A; Lakoski, Susan G; Jenny, Nancy S

    2010-01-01

    Justification for the Use of Statins in Primary Prevention: An Intervention Trial Using Rosuvastatin (JUPITER) reported reduced cardiovascular and all-cause mortality with statin treatment in patients with elevated C-reactive protein (CRP) and average cholesterol levels who were not eligible for lipid-lowering treatment on the basis of existing guidelines. The aim of this study was to determine the prevalence of eligibility and mortality in a general population sample on the basis of eligibility for statin treatment using the JUPITER criteria. The study group consisted of 30,229 participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort, an observational study of US African American and white participants aged > or =45 years, enrolled in their homes from 2003 to 2007 and followed biannually by telephone. Among 11,339 participants age eligible for JUPITER and without vascular diagnoses or using lipid-lowering treatment, 21% (n = 2,342) met JUPITER entry criteria. Compared with JUPITER participants, they had similar low-density lipoprotein cholesterol and CRP levels, were more often women, were more often black, had metabolic syndrome, and used aspirin for cardioprotection. Over 3.5 years of follow-up, the mortality rate in REGARDS participants eligible for JUPITER was 1.17 per 100 patient-years (95% confidence interval 0.94 to 1.42). Compared with those otherwise JUPITER eligible who had CRP levels or =2 mg/L had a multivariate-adjusted relative risk of 1.5 (95% confidence interval 1.1 to 2.2) for total mortality. In conclusion, 21% not otherwise eligible would be newly eligible for lipid lowering treatment on the basis of JUPITER trial eligibility.

  6. Statins-More Than Just Plaque Stabilisation

    Directory of Open Access Journals (Sweden)

    Ashish K Khanna

    2008-01-01

    Perioperative statin therapy seems to be associated with a survival benefit, with a variable effect on postoperative cardiovascular morbidity. The available evidence also suggests that, there may be a benefit from including statins in the therapy for treatment of sepsis. Larger prospective, randomized clinical trials are needed to confirm these observations and to determine the optimal timing and duration of statin therapy in the perioperative setting.

  7. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.

    LENUS (Irish Health Repository)

    Sattar, Naveed

    2010-02-27

    Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes.

  8. Serum PCSK9 Levels Distinguish Individuals Who Do Not Respond to High-Dose Statin Therapy with the Expected Reduction in LDL-C

    Directory of Open Access Journals (Sweden)

    Beth A. Taylor

    2014-01-01

    Full Text Available The purpose of the present report was to examine whether proprotein convertase subtilisin/kexin type 9 (PCSK9 levels differ in individuals who do not exhibit expected reductions in low density lipoprotein cholesterol (LDL-C with statin therapy. Eighteen nonresponder subjects treated with 80 mg atorvastatin treatment for 6 months without substantial reductions in LDL-C (ΔLDL-C: 2.6 ± 11.4% were compared to age- and gender-matched atorvastatin responders (ΔLDL-C: 50.7 ± 8.5% and placebo-treated subjects (ΔLDL-C: 9.9 ± 21.5%. Free PCSK9 was marginally higher in nonresponders at baseline (P=0.07 and significantly higher in atorvastatin responders after 6 months of treatment (P=0.04. The change in free PCSK9 over 6 months with statin treatment was higher (P<0.01 in atorvastatin responders (134.2 ± 131.5 ng/mL post- versus prestudy than in either the nonresponders (39.9 ± 87.8 ng/mL or placebo subjects (27.8 ± 97.6 ng/mL. Drug compliance was not lower in the nonresponders as assessed by pill counts and poststudy plasma atorvastatin levels. Serum PCSK9 levels, both at baseline and in response to statin therapy, may differentiate individuals who do versus those who do not respond to statin treatment.

  9. Immune-mediated statin myopathy.

    Science.gov (United States)

    Loganathan, Priyadarshini; Oddis, Chester V; Aggarwal, Rohit

    2016-01-01

    Statin-induced necrotizing autoimmune myopathy (SINAM) is associated with a unique clinical 5 phenotype of severe proximal muscle weakness during or after exposure to statins in patients with high creatine kinase (CK) levels. Electromyography (EMG) and muscle biopsy reveal features of a necrotizing myopathy and the anti-HMGCR autoantibody is frequently detected. Treatment requires a combination of statin discontinuation as well as immunomodulatory or immunosuppressive therapy. HLA typing (HLADRB1*1101) is strongly associated with anti-10 HMGCR autoantibody positivity in statin-exposed patients. It is well documented that statin triggers autoimmune disease in those with a genetic susceptibility. With the commercial availability of an accurate ELISA test, the natural history of the disease and its phenotypic features are becoming increasingly understood.

  10. Cardiorespiratory fitness attenuates risk for major adverse cardiac events in hyperlipidemic men and women independent of statin therapy: The Henry Ford ExercIse Testing Project.

    Science.gov (United States)

    Hung, Rupert K; Al-Mallah, Mouaz H; Qadi, Mohamud A; Shaya, Gabriel E; Blumenthal, Roger S; Nasir, Khurram; Brawner, Clinton A; Keteyian, Steven J; Blaha, Michael J

    2015-08-01

    We sought to evaluate the effect of cardiorespiratory fitness (CRF) in predicting mortality, myocardial infarction (MI), and revascularization in patients with hyperlipidemia after stratification by gender and statin therapy. This retrospective cohort study included 33,204 patients with hyperlipidemia (57 ± 12 years old, 56% men, 25% black) who underwent physician-referred treadmill stress testing at the Henry Ford Health System from 1991 to 2009. Patients were stratified by gender, baseline statin therapy, and estimated metabolic equivalents from stress testing. We computed hazard ratios using Cox regression models after adjusting for demographics, cardiac risk factors, comorbidities, pertinent medications, interaction terms, and indication for stress testing. There were 4,851 deaths, 1,962 MIs, and 2,686 revascularizations over a median follow-up of 10.3 years. In men and women not on statin therapy and men and women on statin therapy, each 1-metabolic equivalent increment in CRF was associated with hazard ratios of 0.86 (95% CI 0.85-0.88), 0.83 (95% CI 0.81-0.85), 0.85 (95% CI 0.83-0.87), and 0.84 (95% CI 0.81-0.87) for mortality; 0.93 (95% CI 0.90-0.96), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.86-0.92), and 0.90 (95% CI 0.86-0.95) for MI; and 0.91 (95% CI 0.88-0.93), 0.87 (95% CI 0.83-0.91), 0.89 (95% CI 0.87-0.92), and 0.90 (95% CI 0.86-0.94) for revascularization, respectively. No significant interactions were observed between CRF and statin therapy (P > .23). Higher CRF attenuated risk for mortality, MI, and revascularization independent of gender and statin therapy in patients with hyperlipidemia. These results reinforce the prognostic value of CRF and support greater promotion of CRF in this patient population. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Guidelines for safe practice of stereotactic body (ablative) radiation therapy

    International Nuclear Information System (INIS)

    Foote, Matthew; Barry, Tamara; Bailey, Michael; Smith, Leigh; Seeley, Anna; Siva, Shankar; Hegi-Johnson, Fiona; Booth, Jeremy; Ball, David; Thwaites, David

    2015-01-01

    The uptake of stereotactic ablative body radiation therapy (SABR) / stereotactic body radiation therapy (SBRT) worldwide has been rapid. The Australian and New Zealand Faculty of Radiation Oncology (FRO) assembled an expert panel of radiation oncologists, radiation oncology medical physicists and radiation therapists to establish guidelines for safe practice of SABR. Draft guidelines were reviewed by a number of international experts in the field and then distributed through the membership of the FRO. Members of the Australian Institute of Radiography and the Australasian College of Physical Scientists and Engineers in Medicine were also asked to comment on the draft. Evidence-based recommendations (where applicable) address aspects of departmental staffing, procedures and equipment, quality assurance measures, as well as organisational considerations for delivery of SABR treatments. Central to the guidelines is a set of key recommendations for departments undertaking SABR. These guidelines were developed collaboratively to provide an educational guide and reference for radiation therapy service providers to ensure appropriate care of patients receiving SABR.

  12. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge

    OpenAIRE

    Elam, Marshall B.; Majumdar, Gipsy; Mozhui, Khyobeni; Gerling, Ivan C.; Vera, Santiago R.; Fish-Trotter, Hannah; Williams, Robert W.; Childress, Richard D.; Raghow, Rajendra

    2017-01-01

    Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate change...

  13. Statins, inflammation and deep vein thrombosis: a systematic review

    Science.gov (United States)

    Rodriguez, April L.; Wojcik, Brandon M.; Wrobleski, Shirley K.; Myers, Daniel D.; Wakefield, Thomas W.

    2012-01-01

    Venous thromboembolism (VTE) includes both deep vein thrombosis (DVT) and pulmonary embolism. The 2009 JUPITER trial showed a significant decrease in DVT in non-hyperlipidemic patients, with elevated C-reactive protein (CRP) levels, treated with rosuvastatin. The effects of statins on thrombosis are unclear, prompting this literature review. A literature search was performed (1950 to February 2011) with MEDLINE, EMBASE, and PUBMED databases including the following keywords: “statins”, “hydroxymethylglutaryl-CoA reductase inhibitors”, “VTE”, “PE”, “DVT”, and either “anti-coagulation” or “inflammation”. Editorials, reviews, case reports, meta-analysis and duplicates were excluded. Inflammatory biomarkers of DVT, include interleukin (IL)-6, CRP, IL-8, and monocyte chemotactic protein 1 (MCP-1). Statin therapy reduces IL-6 expression of CRP and MCP-1, usually elevated in VTE. Reduction of IL-6 induced MCP-1 has been linked to vein wall fibrosis, promoting post thrombotic syndrome (PTS) and recurrent DVT in patients. Also, our review suggests that the anti-thrombotic effects are likely exhibited through the anti-inflammatory properties of statins. This work supports that statin therapy has the ability to decrease the incidence and recurrence of VTE and the potential to decrease PTS. This is mainly due to the anti-inflammatory effects of statins and may explain why normolipidemic patients, with elevated CRP, appear to have the greatest reduction in VTE. Given their low risk of bleeding, statins have the potential to serve as a safe adjunctive pharmacological therapy to current treatments in select patients with VTE, however further investigations into this concept are needed and essential. PMID:22278047

  14. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale.

    Science.gov (United States)

    Teramoto, Tamio; Kondo, Akira; Kiyosue, Arihiro; Harada-Shiba, Mariko; Ishigaki, Yasushi; Tobita, Kimimasa; Kawabata, Yumiko; Ozaki, Asuka; Baccara-Dinet, Marie T; Sata, Masataka

    2017-06-17

    Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone). ClinicalTrials.gov number: NCT02584504.

  15. Statin therapy reduces inappropriate shock in non-ischemic patients with mild heart failure

    DEFF Research Database (Denmark)

    Ruwald, Anne-Christine H.; Zareba, Wojciech; Jons, Christian

    2013-01-01

    tachycardia zone of 170 to 199 bpm (arm A), high-rate cutoff with a ventricular tachycardia zone ≥200 bpm (arm B), or 60-second-delayed therapy (arm C). The end points of inappropriate therapy, appropriate therapy, and death were assessed among 485 patients with and 998 without diabetes mellitus. Innovative...

  16. [Broader indication for treatment with statins; the 'heart protection study'

    NARCIS (Netherlands)

    Stalenhoef, A.F.H.; Stuyt, P.M.J.

    2002-01-01

    The introduction of statins has been a breakthrough in the treatment of hypercholesterolaemia. Statins are safe and effective in reducing the risk of coronary heart disease in the general population. The 'Heart protection study' has provided evidence for the benefit of statin treatment in much

  17. Effects of statin therapy on cerebrovascular and renal outcomes in patients with predialysis advanced chronic kidney disease and dyslipidemia.

    Science.gov (United States)

    Chung, Chang-Min; Lin, Ming-Shyan; Hsu, Jen-Te; Hsiao, Ju-Feng; Chang, Shih-Tai; Pan, Kuo-Li; Lin, Chun-Liang; Lin, Yu-Sheng

    Treatment with statin may be beneficial for patients with chronic kidney disease (CKD). However, the debate over the clinical importance of statin in patients with predialysis advanced CKD remains unresolved. The objective of the article was to evaluate the effect of statin on mortality, cerebrovascular, and renal outcomes in patients with predialysis advanced CKD and dyslipidemia. Data on predialysis advanced CKD patients were retrieved from the National Health Insurance Research Database based on the guidelines for prescribing regular erythropoietin-stimulating agent in CKD patients. Patients with dyslipidemia were further selected and divided into 2 groups by their statin use after the prescribed erythropoietin-stimulating agent. All-cause mortality and cerebrovascular and renal outcomes were analyzed after propensity score matching. There were 2016 and 14,412 patients in the statin and nonstatin groups. Their average follow-up periods were 3.7 and 3.0 years, respectively. After 1:2 propensity score matching, the annual all-cause mortality rate was higher in the nonstatin than in the statin group (143.99 vs 109.50 per 1000 person-years; P statin group (1269.45 vs 1095.00 per 1000 person-years; P = .002). Adverse events were not significant between the 2 groups. Statins may reduce the all-cause mortality and reduced the risk of dialysis in patients with predialysis advanced CKD and dyslipidemia. However, statins have no impact on ischemic-hemorrhage stroke. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  18. Statin Therapy and the Development of Cerebral Amyloid Angiopathy—A Rodent in Vivo Approach

    Directory of Open Access Journals (Sweden)

    Björn Reuter

    2016-01-01

    Full Text Available Background: Cerebral amyloid angiopathy (CAA is characterized by vascular deposition of amyloid β (Aβ with a higher incidence of cerebral microbleeds (cMBs and spontaneous hemorrhage. Since statins are known for their benefit in vascular disease we tested for the effect on CAA. Methods: APP23-transgenic mice received atorvastatin-supplemented food starting at the age of eight months (n = 13, 12 months (n = 7, and 16 months (n = 6, respectively. Controls (n = 16 received standard food only. At 24 months of age cMBs were determined with T2*-weighted 9.4T magnetic resonance imaging and graded by size. Results: Control mice displayed an average of 35 ± 18.5 cMBs (mean ± standard deviation, compared to 29.3 ± 9.8 in mice with eight months (p = 0.49, 24.9 ± 21.3 with 12 months (p = 0.26, and 27.8 ± 15.4 with 16 months of atorvastatin treatment (p = 0.27. In combined analysis treated mice showed lower absolute numbers (27.4 ± 15.6, p = 0.16 compared to controls and also after adjustment for cMB size (p = 0.13. Conclusion: Despite to a non-significant trend towards fewer cMBs our results failed to provide evidence for beneficial effects of long-term atorvastatin treatment in the APP23-transgenic mouse model of CAA. A higher risk for bleeding complications was not observed.

  19. Statin intolerance - a question of definition.

    Science.gov (United States)

    Algharably, Engi Abdel-Hady; Filler, Iris; Rosenfeld, Stephanie; Grabowski, Katja; Kreutz, Reinhold

    2017-01-01

    Statin therapy is the backbone of pharmacologic therapy for low-density lipoproteins cholesterol lowering and plays a pivotal role in cardiovascular disease prevention. Statin intolerance is understood as the inability to continue using a statin to reduce individual cardiovascular risk sufficiently, due to the development of symptoms or laboratory abnormalities attributable to the initiation or dose escalation of a statin. Muscle symptoms are the most common side effects observed. Areas covered: The main aim of this article is to present a review on published definitions of statin intolerance. In addition, a brief review on clinical aspects and risk factors of statin intolerance is provided and features for a common definition for statin intolerance are suggested. Expert opinion: A definition of statin intolerance by major drug regulatory agencies is not available. In clinical studies, different definitions are chosen and results are not comparable; different medical associations do not agree on one common definition. There is an unmet need to establish a common definition of statin intolerance to ensure an appropriate clinical use of this important drug class. Further work is required to develop a consensus definition on statin intolerance that could have significant positive impact on both research and clinical management.

  20. Hypercholesterolemia, Stroke And Statins

    Directory of Open Access Journals (Sweden)

    Prabhakar S

    2005-01-01

    Full Text Available The link between serum cholesterol levels and the incidence of stroke still remain to be established. There are conflicting reports from a series of observational cohort studies. However, clinical trials with HMG CoA reductase inhibitors (also called statins have shown that cholesterol lowering therapy used in the primary and secondary prevention of myocardial infarction significantly reduced cardiovascular events including strokes. Meta analysis of trials with statins have shown a relative risk reduction in stroke of 12 to 48% in patients with coronary heart disease after MI. It has been postulated that the clinical action of statins is the result of pleiotropic / antiatherogenic effects rather than simply a reduction in cholesterol. The putative beneficial effect of statins in stroke involve blocking of macrophage and platelet activation, improvement of endothelial cell vasomotor function, enhancement of endothelial fibrinolytic function, immunosuppressive and anti-inflammatory action, inhibition of smooth muscle cell proliferation and particularly enhancement of endothelial nitric oxide synthase (eNOS.

  1. Trends in Use of High-Intensity Statin Therapy After Myocardial Infarction, 2011 to 2014.

    Science.gov (United States)

    Rosenson, Robert S; Farkouh, Michael E; Mefford, Matthew; Bittner, Vera; Brown, Todd M; Taylor, Ben; Monda, Keri L; Zhao, Hong; Dai, Yuling; Muntner, Paul

    2017-06-06

    Data prior to 2011 suggest that a low percentage of patients hospitalized for acute coronary syndromes filled high-intensity statin prescriptions upon discharge. Black-box warnings, generic availability of atorvastatin, and updated guidelines may have resulted in a change in high-intensity statin use. The aim of this study was to examine trends and predictors of high-intensity statin use following hospital discharge for myocardial infarction (MI) between 2011 and 2014. Secular trends in high-intensity statin use following hospital discharge for MI were analyzed among patients 19 to 64 years of age with commercial health insurance in the MarketScan database (n = 42,893) and 66 to 75 years of age with U.S. government health insurance through Medicare (n = 75,096). Patients filling statin prescriptions within 30 days of discharge were included. High-intensity statins included atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg. The percentage of beneficiaries whose first statin prescriptions filled following hospital discharge for MI were for high-intensity doses increased from 33.5% in January through March 2011 to 71.7% in October through November 2014 in MarketScan and from 24.8% to 57.5% in Medicare. Increases in high-intensity statin use following hospital discharge occurred over this period among patients initiating treatment (30.6% to 72.0% in MarketScan and 21.1% to 58.8% in Medicare) and those taking low- or moderate-intensity statins prior to hospitalization (from 27.8% to 62.3% in MarketScan and from 12.6% to 45.1% in Medicare). In 2014, factors associated with filling high-intensity statin prescriptions included male sex, filling beta-blocker and antiplatelet agent prescriptions, and attending cardiac rehabilitation within 30 days following discharge. The use of high-intensity statins following hospitalization for MI increased progressively from 2011 through 2014. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier

  2. STATINS AND URSODEOXYCHOLIC ACID: COOPERATION OR NEUTRALITY?

    Directory of Open Access Journals (Sweden)

    I. N. Grigorieva

    2016-01-01

    Full Text Available Results of combined therapy of gallstone disease (GSD, non-alcoholic fatty liver disease (NAFLD, non-alcoholic steatohepatitis (NASH and hypercholesterolemia (HCE with statins and ursodeoxycholic acid (UDCA are analyzed. In GSD statin therapy was often accompanied with reduction of bile lithogenicity but did not always accelerate stone litholysis under their combination with UDCA. Statin induced liver injuries are often observed in NAFLD and NASH, adjuvant UDCA therapy shown positive effect on inflammatory and histological liver parameters in these diseases. Serum lipid levels in patients with HCE were reduced most effectively with statin combined with UDCA. Combined therapy with statin and UDCA is recommended in patient with HCE and chronic liver diseases.

  3. STATINS AND URSODEOXYCHOLIC ACID: COOPERATION OR NEUTRALITY?

    Directory of Open Access Journals (Sweden)

    I. N. Grigorieva

    2009-01-01

    Full Text Available Results of combined therapy of gallstone disease (GSD, non-alcoholic fatty liver disease (NAFLD, non-alcoholic steatohepatitis (NASH and hypercholesterolemia (HCE with statins and ursodeoxycholic acid (UDCA are analyzed. In GSD statin therapy was often accompanied with reduction of bile lithogenicity but did not always accelerate stone litholysis under their combination with UDCA. Statin induced liver injuries are often observed in NAFLD and NASH, adjuvant UDCA therapy shown positive effect on inflammatory and histological liver parameters in these diseases. Serum lipid levels in patients with HCE were reduced most effectively with statin combined with UDCA. Combined therapy with statin and UDCA is recommended in patient with HCE and chronic liver diseases.

  4. Effect of high-dose oral multivitamins and minerals in participants not treated with statins in the randomized Trial to Assess Chelation Therapy (TACT).

    Science.gov (United States)

    Issa, Omar M; Roberts, Rhonda; Mark, Daniel B; Boineau, Robin; Goertz, Christine; Rosenberg, Yves; Lewis, Eldrin F; Guarneri, Erminia; Drisko, Jeanne; Magaziner, Allan; Lee, Kerry L; Lamas, Gervasio A

    2018-01-01

    In a prespecified subgroup analysis of participants not on statin therapy at baseline in the TACT, a high-dose complex oral multivitamins and multimineral regimen was found to have a large unexpected benefit compared with placebo. The regimen tested was substantially different from any vitamin regimen tested in prior clinical trials. To explore these results, we performed detailed additional analyses of participants not on statins at enrollment in TACT. TACT was a factorial trial testing chelation treatments and a 28-component high-dose oral multivitamins and multiminerals regimen versus placebo in post-myocardial infarction (MI) patients 50 years or older. There were 460 (27%) of 1,708 TACT participants not taking statins at baseline, 224 (49%) were in the active vitamin group and 236 (51%) were in the placebo group. Patients were enrolled at 134 sites around the United States and Canada. Daily high-dose oral multivitamins and multiminerals (6 tablets, active or placebo). The primary end point of TACT was time to the first occurrence of any component of the composite end point: all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for angina. The primary end point occurred in 137 nonstatin participants (30%), of which 51 (23%) of 224 were in the active group and 86 (36%) of 236 were taking placebo (hazard ratio, 0.62; 95% confidence interval, 0.44-0.87; P=.006). Results in the key TACT secondary end point, a combination of cardiovascular mortality, stroke, or recurrent MI, was consistent in favoring the active vitamin group (hazard ratio, 0.46; 95% confidence interval, 0.28-0.75; P=.002). Multiple end point analyses were consistent with these results. High-dose oral multivitamin and multimineral supplementation seem to decrease combined cardiac events in a stable, post-MI population not taking statin therapy at baseline. These unexpected findings are being retested in the ongoing TACT2. Copyright © 2017 The Authors. Published by Elsevier

  5. Influence of statin therapy at time of stroke onset on functional outcome among patients with atrial fibrillation.

    Science.gov (United States)

    Ko, Darae; Thigpen, Jonathan L; Otis, James A; Forster, Kristen; Henault, Lori; Quinn, Emily; Tripodis, Yorghos; Berger, Peter B; Limdi, Nita; Hylek, Elaine M

    2017-01-15

    Statin pretreatment has been associated with reduced infarct volume in nonlacunar strokes. The effect of statins on functional outcomes of strokes related to atrial fibrillation (AF) is unknown. We aimed to define the influence of prestroke statin use on functional outcome in AF. We assembled a cohort of consecutive ischemic stroke patients from 2006 to 2010. All patients underwent CT or MRI and were adjudicated by site investigators. AF was confirmed by electrocardiogram in 100% of patients. Site neurologists blinded to the study hypothesis affirmed the type of stroke and assessed the severity of disability at the time of hospital discharge. The frequency of death at 30-days was calculated. Ischemic stroke (n=1030) resulted in a severe neurological deficit or death (modified Rankin scale ≥4) at 30days in 711 patients (69%). Using multivariable logistic regression models adjusting for factors associated with statin treatment and factors associated with functional outcome, prestroke statin use was associated with a 32% reduction in frequency of severe stroke (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.50-0.92; P=0.011). Other independent factors associated with severe stroke included older age, female sex, non-White race, diabetes mellitus, prior ischemic stroke, prior venous thromboembolism, and dementia. Ischemic strokes in AF are associated with high mortality and morbidity. Statin use at time of stroke onset among patients with AF was associated in this study with less severe stroke and warrant validation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  6. Management of statin-intolerant patient.

    Science.gov (United States)

    Arca, M; Pigna, G; Favoccia, C

    2012-06-01

    Large scale clinical trials have undoubtedly demonstrated that statins are effective in reducing cardiovascular events and all-cause mortality in almost all patient populations. Also the short and long-term safety of statin therapy has been well established in the majority of treated patients. Nevertheless, intolerance to statins must be frequently faced in the clinical practice. The most commonly observed adverse effects of statins are muscle symptoms and elevation of hepatic aminotransferase and creatinine kinase (CK) levels. Overall, myalgia (muscle pain with or without plasma CK elevations) and a single abnormally elevated liver function test constitute approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in the patients and are likely to reduce patient's adherence and, consequently, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve knowledge on the clinical aspects of side effects of statins and the ability to manage patients with intolerance to statins. Numerous different approaches to statin-intolerant patients have been suggested, but an evidence-based consensus is difficult to be reached due to the lack of controlled trials. Therefore, it might be useful to review protocols and procedures to control statin intolerance. The first step in managing intolerant patients is to determine whether the adverse events are indeed related to statin therapy. Then, the switching to another statin or lower dosage, the alternate dosing options and the use of non-statin compounds may be practical strategies. However, the cardiovascular benefit of these approaches has not been established, so that their use has to be employed after a careful clinical assessment of each patient.

  7. Impact of statin therapy on plasma adiponectin concentrations: A systematic review and meta-analysis of 43 randomized controlled trial arms.

    Science.gov (United States)

    Chruściel, Piotr; Sahebkar, Amirhossein; Rembek-Wieliczko, Magdalena; Serban, Maria-Corina; Ursoniu, Sorin; Mikhailidis, Dimitri P; Jones, Steven R; Mosteoru, Svetlana; Blaha, Michael J; Martin, Seth S; Rysz, Jacek; Toth, Peter P; Lip, Gregory Y H; Pencina, Michael J; Ray, Kausik K; Banach, Maciej

    2016-10-01

    The effect of statin therapy on plasma adiponectin levels has not been conclusively studied. Therefore, we aimed to evaluate this effect through a systematic review and meta-analysis of available randomized controlled trials (RCTs). Quantitative data synthesis was performed using a random-effects model with weighted mean difference (WMD) and 95% confidence interval (CI) as summary statistics. In 30 studies (43 study arms) with 2953 participants, a significant increase in plasma adiponectin levels was observed after statin therapy (WMD: 0.57 μg/mL, 95% CI: 0.18, 0.95, p = 0.004). In subgroup analysis, atorvastatin, simvastatin, rosuvastatin, pravastatin and pitavastatin were found to change plasma adiponectin concentrations by 0.70 μg/mL (95% CI: -0.26, 1.65), 0.50 μg/mL (95% CI: -0.44, 1.45), -0.70 μg/mL (95% CI: -1.08, -0.33), 0.62 μg/mL (95% CI: -0.12, 1.35), and 0.51 μg/mL (95% CI: 0.30, 0.72), respectively. With respect to duration of treatment, there was a significant increase in the subset of trials lasting ≥12 weeks (WMD: 0.88 μg/mL, 95% CI: 0.19, 1.57, p = 0.012) but not in the subset of statin-induced elevation of plasma adiponectin and changes in plasma low density lipoprotein cholesterol levels (slope: 0.04; 95% CI: 0.01, 0.06; p = 0.002). The meta-analysis showed a significant increase in plasma adiponectin levels following statin therapy. Although statins are known to increase the risk for new onset diabetes mellitus, our data might suggest that the mechanism for this is unlikely to be due to a reduction in adiponectin expression. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Antiatherosclerotic effects of long-term maximally intensive statin therapy after acute coronary syndrome: insights from Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin.

    Science.gov (United States)

    Puri, Rishi; Nissen, Steven E; Shao, Mingyuan; Ballantyne, Christie M; Barter, Philip J; Chapman, M John; Erbel, Raimund; Libby, Peter; Raichlen, Joel S; Uno, Kiyoko; Kataoka, Yu; Nicholls, Stephen J

    2014-11-01

    Patients with acute coronary syndromes (ACS) display diffuse coronary atheroma instability and heightened risk of early and late recurrent coronary events. We compared the long-term antiatherosclerotic efficacy of high-intensity statins in patients with ACS when compared with stable disease. Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) used serial intravascular ultrasound measures of coronary atheroma volume in patients treated with rosuvastatin 40 mg or atorvastatin 80 mg for 24 months. The overall effect of high-intensity statins on the change in coronary percent atheroma volume and major adverse cardiovascular events (death/nonfatal myocardial infarction/coronary revascularization) were evaluated in this post hoc analysis. When compared with non-ACS patients (n=678), patients with ACS (n=361) were younger, actively smoking, and have had a previous myocardial infarction (all P<0.001). At baseline, patients with ACS exhibited lower high-density lipoprotein cholesterol (43.5±11 versus 45.8±11 mg/dL; P=0.002), a higher apolipoprotein B: apolipoprotein A-1 ratio (0.90±0.24 versus 0.83±0.24; P<0.001) and greater percent atheroma volume (37.3±8.5% versus 35.9±8.1%; P=0.01) when compared with non-ACS patients. Despite similar achieved levels of lipid and inflammatory markers after high-intensity statin therapy, patients with ACS demonstrated greater percent atheroma volume regression than non-ACS patients (-1.46±0.14 versus -0.89±0.13; P=0.003). After propensity-weighted multivariable adjustment, baseline percent atheroma volume (P<0.001) and an ACS clinical presentation (P=0.02) independently associated with plaque regression. The 24-month major adverse cardiovascular events-free survival was similar between patients with ACS and non-ACS (90.6 versus 92.9%; P=0.25). Long-term high-intensity statin therapy caused greater plaque regression and comparable major adverse cardiovascular events rates in

  9. Effect of statins as modulators of CD39+ tregs in patients with rheumatoid arthritis who were unsuccessfully treated with methotrexate

    Directory of Open Access Journals (Sweden)

    Mohammed H Abu-Zaid

    2018-01-01

    Conclusion Combination therapy with AV and ETA provides an added immunomodulatory benefit through enhancement of the immune suppression mediated by CD39+ Treg cells. Therefore, statins can be used safely with antitumor necrosis factor drugs to control disease activity and atherosclerotic changes in patients with RA, who are treated unsuccessfully with MTX.

  10. Association between statin-associated myopathy and skeletal muscle damage.

    OpenAIRE

    Mohaupt Markus G; Karas Richard H; Babiychuk Eduard B; Sanchez-Freire Verónica; Monastyrskaya Katia; Iyer Lakshmanan; Hoppeler Hans; Breil Fabio; Draeger Annette

    2009-01-01

    BACKGROUND Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. METHODS We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin associated myopathy 29 were currently taking a statin and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking stat...

  11. Moderate-intensity statin therapy seems ineffective in primary cardiovascular prevention in patients with type 2 diabetes complicated by nephropathy. A multicenter prospective 8 years follow up study.

    Science.gov (United States)

    Sasso, Ferdinando Carlo; Lascar, Nadia; Ascione, Antonella; Carbonara, Ornella; De Nicola, Luca; Minutolo, Roberto; Salvatore, Teresa; Rizzo, Maria Rosaria; Cirillo, Plinio; Paolisso, Giuseppe; Marfella, Raffaele

    2016-10-13

    Although numerous studies and metanalysis have shown the beneficial effect of statin therapy in CVD secondary prevention, there is still controversy such the use of statins for primary CVD prevention in patients with DM. The purpose of this study was to evaluate the occurrence of total major adverse cardio-vascular events (MACE) in a cohort of patients with type 2 diabetes complicated by nephropathy treated with statins, in order to verify real life effect of statin on CVD primary prevention. We conducted an observational prospective multicenter study on 564 patients with type 2 diabetic nephropathy free of cardiovascular disease attending 21 national outpatient diabetes clinics and followed them up for 8 years. 169 of them were treated with statins (group A) while 395 were not on statins (group B). Notably, none of the patients was treated with a high-intensity statin therapy according to last ADA position statement. Total MACE occurred in 32 patients from group A and in 68 patients from group B. Fatal MACE occurred in 13 patients from group A and in 30 from group B; nonfatal MACE occurred in 19 patients from group A and in 38 patients from group B. The analysis of the Kaplan-Meier survival curves showed a not statistically significant difference in the incidence of total (p 0.758), fatal (p 0.474) and nonfatal (p 0.812) MACE between the two groups. HbA1c only showed a significant difference in the incidence of MACE between the two groups (HR 1.201, CI 1.041-1.387, p 0.012). These findings suggest that, in a real clinical setting, moderate-intensity statin treatment is ineffective in cardiovascular primary prevention for patients with diabetic nephropathy. Trial registration ClinicalTrials.gov Identifier NCT00535925. Date of registration: September 24, 2007, retrospectively registered.

  12. Identification of Patients with Statin Intolerance in a Managed Care Plan: A Comparison of 2 Claims-Based Algorithms.

    Science.gov (United States)

    Bellows, Brandon K; Sainski-Nguyen, Amy M; Olsen, Cody J; Boklage, Susan H; Charland, Scott; Mitchell, Matthew P; Brixner, Diana I

    2017-09-01

    While statins are safe and efficacious, some patients may experience statin intolerance or treatment-limiting adverse events. Identifying patients with statin intolerance may allow optimal management of cardiovascular event risk through other strategies. Recently, an administrative claims data (ACD) algorithm was developed to identify patients with statin intolerance and validated against electronic medical records. However, how this algorithm compared with perceptions of statin intolerance by integrated delivery networks remains largely unknown. To determine the concurrent validity of an algorithm developed by a regional integrated delivery network multidisciplinary panel (MP) and a published ACD algorithm in identifying patients with statin intolerance. The MP consisted of 3 physicians and 2 pharmacists with expertise in cardiology, internal medicine, and formulary management. The MP algorithm used pharmacy and medical claims to identify patients with statin intolerance, classifying them as having statin intolerance if they met any of the following criteria: (a) medical claim for rhabdomyolysis, (b) medical claim for muscle weakness, (c) an outpatient medical claim for creatinine kinase assay, (d) fills for ≥ 2 different statins excluding dose increases, (e) decrease in statin dose, or (f) discontinuation of a statin with a subsequent fill for a nonstatin lipid-lowering therapy. The validated ACD algorithm identified statin intolerance as absolute intolerance with rhabdomyolysis; absolute intolerance without rhabdomyolysis (i.e., other adverse events); or as dose titration intolerance. Adult patients (aged ≥ 18 years) from the integrated delivery network with at least 1 prescription fill for a statin between January 1, 2011, and December 31, 2012 (first fill defined the index date) were identified. Patients with ≥ 1 year pre- and ≥ 2 years post-index continuous enrollment and no statin prescription fills in the pre-index period were included. The MP and

  13. Prescription and adherence to statins of patients with coronary artery disease and hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Mansur Antonio P.

    2001-01-01

    Full Text Available OBJECTIVE: Statins have proved to be safe and effective in the secondary prevention of coronary artery disease, but the level of prescription and the reasons for nonadherence to treatment in many coronariopathy treatment centers has not been determined. The purpose of this study was to identify reasons for nonadherence to statin therapy. METHODS: We analyzed 207 consecutive patients with coronary artery disease and hypercholesterolemia (total cholesterol > or = 200mg/dL or LDL - cholesterol > or = 130mg/dL. Patients' average age was 61.7±10 year; 111 (53.6% male were and 94 (46.6% were female. We analyzed the level of prescription and adherence to treatment with statins. RESULTS: Statins were prescribed for 139 (67% patients, but only 85 (41% used the drug. In spite of being indicated, statins were not prescribed in 68 (33% patients. Of 54 (26% patients, nonadherent to statins, 67% did not use the drug due to its high cost, 31% due to the lack of instruction, and only 2% due to side effects. Total cholesterol (260.3±42.2 vs 226.4±51.9; p<0.0001 and LDL cholesterol (174.6±38.1 vs 149.6±36.1; p<0.0001 were lower in patients on medication. HDL-cholesterol increased from 37.6±9.6 to 41.5±12.9mg/dL (p=0.02, and triglycerides were not modified in patients using statins. CONCLUSION: The prescription of statins in patients with coronary artery disease and dyslipidemia is high; however, its adherence is far from satisfactory, due to the high cost of the medication. Reduction in total cholesterol and LDL cholesterol levels did not reach the targets recommended by the Brazilian Consensus on Dyslipidemia.

  14. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

    Science.gov (United States)

    Mega, J L; Stitziel, N O; Smith, J G; Chasman, D I; Caulfield, M; Devlin, J J; Nordio, F; Hyde, C; Cannon, C P; Sacks, F; Poulter, N; Sever, P; Ridker, P M; Braunwald, E; Melander, O; Kathiresan, S; Sabatine, M S

    2015-06-06

    Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, pgenetic risk category was 1·72 (1·55-1·92, pgenetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high

  15. Do immigrants from Turkey, Pakistan and Ex-Yugoslavia with newly diagnosed type 2 diabetes initiate recommended statin therapy to the same extent as Danish-born residents? A nationwide register study

    DEFF Research Database (Denmark)

    Sanchez-Ramirez, Diana; Krasnik, Allan; Kildemoes, Helle Wallach

    2012-01-01

    PURPOSE: To explore whether newly diagnosed type 2 diabetes patients without previous cardiovascular disease (CVD) initiate preventive statin therapy regardless of ethnic background. METHODS: Using nationwide individual-level registers, we followed a cohort of Danish-born residents and immigrants...... the odds ratios (ORs) of early statin therapy initiation (within 180 days after first GLM dispensing) are the same regardless of ethnic background. While age and gender were included as confounders in the basic model, income was included in the second model as a potential mediating variable. RESULTS....... CONCLUSIONS: Immigrants from Turkey, Pakistan and Ex-Yugoslavia with type 2 diabetes were less likely to initiate statin therapy than Danish-born residents-despite a similar or even higher risk of CVD. The treatment inequities associated with ethnicity were more pronounced in women than men...

  16. Consumer behavior in the setting of over-the-counter statin availability: lessons from the consumer use study of OTC Mevacor.

    Science.gov (United States)

    Brass, Eric P

    2004-11-04

    Despite the proven benefits of statins, large numbers of patients meeting guideline criteria for therapy are not receiving these drugs. It has been suggested that over-the-counter (OTC) availability of statins would allow more consumers to use statins and achieve cardiovascular risk reduction. However, concerns have been raised as to the consumers' ability to self-manage hyperlipidemia and use statins safely. The Consumer Use Study of OTC Mevacor (CUSTOM) was designed to define consumer behaviors in the setting of OTC statin availability. The study was conducted in a simulated OTC setting and allowed consumers to purchase once-daily lovastatin 20 mg. The CUSTOM dataset includes >3,300 consumers who evaluated OTC lovastatin for potential purchase at study sites and follow-up information on purchasers for up to 6 months of self-managed therapy. These data have been analyzed to address consumers' knowledge of their cholesterol concentrations as well as their ability to make OTC use decisions based on their cardiovascular risk, avoid drug-drug interactions, self-manage their cholesterol treatment after deciding to use the OTC product, and maintain interactions with physicians while using lovastatin OTC. The results showed that most study participants appropriately self-selected OTC statin therapy and managed their treatment. Use of OTC statins by consumers needing more intensive statin therapy or facing the risk of potential drug-drug interactions remains an area of concern but occurred infrequently in CUSTOM. These data are important for making an informed risk-benefit decision concerning OTC statin availability.

  17. Effect of Statin Therapy on Incident Type 2 Diabetes Mellitus in Patients With Clinically Manifest Vascular Disease

    NARCIS (Netherlands)

    Van De Woestijne, Anton P.; Van Der Graaf, Yolanda; Westerink, Jan; Nathoe, Hendrik M.; Visseren, Frank L J

    2015-01-01

    Several trials and cohort studies have shown an increased incidence of type 2 diabetes mellitus (T2DM) in patients using statins. Whether this only applies to patients at already high risk for the development of T2DM or for all patients is still a matter of debate. In the present prospective cohort

  18. Progresses towards safe and efficient gene therapy vectors.

    Science.gov (United States)

    Chira, Sergiu; Jackson, Carlo S; Oprea, Iulian; Ozturk, Ferhat; Pepper, Michael S; Diaconu, Iulia; Braicu, Cornelia; Raduly, Lajos-Zsolt; Calin, George A; Berindan-Neagoe, Ioana

    2015-10-13

    The emergence of genetic engineering at the beginning of the 1970's opened the era of biomedical technologies, which aims to improve human health using genetic manipulation techniques in a clinical context. Gene therapy represents an innovating and appealing strategy for treatment of human diseases, which utilizes vehicles or vectors for delivering therapeutic genes into the patients' body. However, a few past unsuccessful events that negatively marked the beginning of gene therapy resulted in the need for further studies regarding the design and biology of gene therapy vectors, so that this innovating treatment approach can successfully move from bench to bedside. In this paper, we review the major gene delivery vectors and recent improvements made in their design meant to overcome the issues that commonly arise with the use of gene therapy vectors. At the end of the manuscript, we summarized the main advantages and disadvantages of common gene therapy vectors and we discuss possible future directions for potential therapeutic vectors.

  19. Management Strategies for Statin-Associated Muscle Symptoms: How Useful Is Same-Statin Rechallenge?

    Science.gov (United States)

    Brennan, Emily T; Joy, Tisha R

    2017-05-01

    Statin-associated muscle symptoms (SAMS) are common. Rechallenge with the same statin (same-statin rechallenge) has recently been included as part of a proposed scoring index for diagnosing SAMS, but data regarding tolerability and efficacy of same-statin rechallenge, compared with other strategies, is minimal. In this study we evaluated the tolerability, percent change in low-density lipoprotein cholesterol (LDL-C), and proportion of patients achieving their LDL-C targets among 3 common management strategies-same-statin rechallenge, switching to a different statin (statin switch), and use of nonstatin medications only. We performed a retrospective analysis of 118 patients referred to our tertiary care centre for management of SAMS, defined as development of muscle-related symptoms with 2 or more statins. Baseline and last follow-up lipid parameters were documented. Patients were classified as tolerant of a strategy if, at their last follow-up, they remained on that strategy. After a median follow-up of 17 months, most (n = 79; 67%) patients were able to tolerate a statin. Tolerability was similar among the 3 treatment strategies (71% same-statin rechallenge vs 53% statin switch vs 57% for nonstatin therapy only; P = 0.11). Those in the same-statin rechallenge and statin switch groups achieved greater LDL-C reductions compared with those who only tolerated nonstatins (-38.8 ± 3.4% vs -36.4 ± 2.9% vs -17.3 ± 4.5%; P = 0.0007). A greater proportion of patients in the same-statin rechallenge group achieved their target LDL-C compared with those in the nonstatin therapy only group (50% vs 15%; odds ratio, 6.8; 95% confidence interval, 1.5-40.7; P = 0.04). Among individuals with a history of SAMS, most will tolerate statin therapy. Same-statin rechallenge was highly tolerable and efficacious. Thus, same-statin rechallenge might warrant increased utilization. Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  20. Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

    Science.gov (United States)

    Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

    2017-03-01

    Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

  1. Impact of statin therapy on central aortic pressures and hemodynamics: principal results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study.

    Science.gov (United States)

    Williams, Bryan; Lacy, Peter S; Cruickshank, J Kennedy; Collier, David; Hughes, Alun D; Stanton, Alice; Thom, Simon; Thurston, Herbert

    2009-01-06

    Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension. CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, -0.1 mm Hg [95% CI, -1.8 to 1.6], P=0.9; change in brachial pulse pressure, -0.02 mm Hg [95% CI, -1.6 to 1.6], P=0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, -0.5 mm Hg [95% CI, -2.3 to 1.2], P=0.5; change in aortic pulse pressure, -0.4 mm Hg [95% CI, -1.9 to 1.0], P=0.6) and had no influence on augmentation index (change in augmentation index, -0.4%; 95% CI, -1.7 to 0.8; P=0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, -1.3 to 1.8; P=0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure-lowering treatment strategy in the factorial design. Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT

  2. Intensive Treat-to-Target Statin Therapy in High-Risk Japanese Patients With Hypercholesterolemia and Diabetic Retinopathy: Report of a Randomized Study.

    Science.gov (United States)

    Itoh, Hiroshi; Komuro, Issei; Takeuchi, Masahiro; Akasaka, Takashi; Daida, Hiroyuki; Egashira, Yoshiki; Fujita, Hideo; Higaki, Jitsuo; Hirata, Ken-Ichi; Ishibashi, Shun; Isshiki, Takaaki; Ito, Sadayoshi; Kashiwagi, Atsunori; Kato, Satoshi; Kitagawa, Kazuo; Kitakaze, Masafumi; Kitazono, Takanari; Kurabayashi, Masahiko; Miyauchi, Katsumi; Murakami, Tomoaki; Murohara, Toyoaki; Node, Koichi; Ogawa, Susumu; Saito, Yoshihiko; Seino, Yoshihiko; Shigeeda, Takashi; Shindo, Shunya; Sugawara, Masahiro; Sugiyama, Seigo; Terauchi, Yasuo; Tsutsui, Hiroyuki; Ueshima, Kenji; Utsunomiya, Kazunori; Yamagishi, Masakazu; Yamazaki, Tsutomu; Yo, Shoei; Yokote, Koutaro; Yoshida, Kiyoshi; Yoshimura, Michihiro; Yoshimura, Nagahisa; Nakao, Kazuwa; Nagai, Ryozo

    2018-06-01

    Diabetes is associated with high risk of cardiovascular (CV) events, particularly in patients with dyslipidemia and diabetic complications. We investigated the incidence of CV events with intensive or standard lipid-lowering therapy in patients with hypercholesterolemia, diabetic retinopathy, and no history of coronary artery disease (treat-to-target approach). In this multicenter, prospective, randomized, open-label, blinded end point study, eligible patients were randomly assigned (1:1) to intensive statin therapy targeting LDL cholesterol (LDL-C) targeting LDL-C 100-120 mg/dL ( n = 2,524). Mean follow-up was 37 ± 13 months. LDL-C at 36 months was 76.5 ± 21.6 mg/dL in the intensive group and 104.1 ± 22.1 mg/dL in the standard group ( P target strategy in high-risk patients deserves further investigation. © 2018 by the American Diabetes Association.

  3. Statin intolerance: Now a solved problem

    Directory of Open Access Journals (Sweden)

    P Sikka

    2011-01-01

    Full Text Available Statins are the most effective and widely used drugs for treating dyslipidemia, a major risk factor for coronary heart disease. These are one of the safest hypolipidemic drugs but many patients are bound to discontinue statins due to their side effects. Hepatotoxicity, myotoxicity and peripheral neuropathy are important out of them. Discontinuation of statins leads to dylipidemia and its grave consequences. Hence, there should be enough strategies for statin intolerant patients, so that they can be saved from these consequences. These side effects can be avoided by the awareness of certain factors viz. potential drug interactions and dose adjustment according to patho-physiology of the patient. Baseline investigations for liver function and muscle toxicity should be done before initiating statin therapy. Here, we are discussing various options for statin intolerant hyperlipidemic patients such as lower and intermittent dosing of statins, alternate hypolipidemic drugs, red yeast rice, supplementation with coenzyme Q10 and vitamin D. A number of hypolipidemic drugs are in trial phases and hold promise for statin intolerant patients.

  4. Cost-effectiveness of raising HDL cholesterol by adding prolonged-release nicotinic acid to statin therapy in the secondary prevention setting: a French perspective.

    Science.gov (United States)

    Roze, S; Ferrières, J; Bruckert, E; Van Ganse, E; Chapman, M J; Liens, D; Renaudin, C

    2007-11-01

    To evaluate the cost-effectiveness of raising high-density lipoprotein cholesterol (HDL-C) with add-on nicotinic acid in statin-treated patients with coronary heart disease (CHD) and low HDL-C, from the French healthcare system perspective. Computer simulation economic modelling incorporating two decision analytic submodels was used. The first submodel generated a cohort of 2000 patients and simulated lipid changes using baseline characteristics and treatment effects from the ARterial Biology for the Investigation of the Treatment Effects of Reducing cholesterol (ARBITER 2) study. Prolonged-release (PR) nicotinic acid (1 g/day) was added in patients with HDL-C costs were accounted from a third party payer perspective [2004 Euros (euro)] and discounted by 3%. Addition of PR nicotinic acid to statin therapy resulted in substantial health gain and increased life expectancy, at a cost well within the threshold (cost-effective in France at a level considered to represent good value for money by reimbursement authorities in Europe. This strategy was highly cost-effective in CHD patients with type 2 diabetes.

  5. Seatbelts in CAR therapy: How Safe Are CARS?

    Directory of Open Access Journals (Sweden)

    Kentaro Minagawa

    2015-05-01

    Full Text Available T-cells genetically redirected with a chimeric antigen receptor (CAR to recognize tumor antigens and kill tumor cells have been infused in several phase 1 clinical trials with success. Due to safety concerns related to on-target/off-tumor effects or cytokine release syndrome, however, strategies to prevent or abate serious adverse events are required. Pharmacologic therapies; suicide genes; or novel strategies to limit the cytotoxic effect only to malignant cells are under active investigations. In this review, we summarize results and toxicities of investigations employing CAR redirected T-cells, with a focus on published strategies to grant safety of this promising cellular application.

  6. The safety of statins in clinical practice.

    Science.gov (United States)

    Armitage, Jane

    2007-11-24

    Statins are effective cholesterol-lowering drugs that reduce the risk of cardiovascular disease events (heart attacks, strokes, and the need for arterial revascularisation). Adverse effects from some statins on muscle, such as myopathy and rhabdomyolysis, are rare at standard doses, and on the liver, in increasing levels of transaminases, are unusual. Myopathy--muscle pain or weakness with blood creatine kinase levels more than ten times the upper limit of the normal range--typically occurs in fewer than one in 10,000 patients on standard statin doses. However, this risk varies between statins, and increases with use of higher doses and interacting drugs. Rhabdomyolysis is a rarer and more severe form of myopathy, with myoglobin release into the circulation and risk of renal failure. Stopping statin use reverses these side-effects, usually leading to a full recovery. Asymptomatic increases in concentrations of liver transaminases are recorded with all statins, but are not clearly associated with an increased risk of liver disease. For most people, statins are safe and well-tolerated, and their widespread use has the potential to have a major effect on the global burden of cardiovascular disease.

  7. AB19. Testosterone replacement therapy: how safe is it?

    Science.gov (United States)

    Goldenberg, Larry

    2014-01-01

    controversies surrounding testosterone replacement therapy (TRT) have been addressed in the past few years. Although the androgenic effects of TRT on normal and malignant prostate cells have been studied for over 70 years, little clinical prospective research exists on the physiological responses of prostate tissues to a wide range of serum testosterone levels. The early, well-designed in vivo studies formed the basis of the concept that testosterone has a threshold or saturation level in all types of androgen-dependent prostate cells. That is, the stimulatory effects of androgens on the prostate reach a point within physiological serum levels above which they no longer have any proliferative effect and serum levels of testosterone and dihydrotestosterone can decrease substantially in both the eugonadal and hypogonadal states without affecting the amount of androgen within the nucleus of the cell. At a certain threshold level (possibly ‘castrate’ level), the intranuclear level of androgen will begin to decrease and the appropriate physiological changes will be triggered. Questions remain as to whether results from experimental studies in the rat can be extrapolated to the situation in humans. Is the human prostate subject to the same homeostatic constraints as has been so well defined in animal experiments, and if so, what is the threshold or saturation level for maximal intracellular androgens and physiological responses in man? The sensitivity of an individual to varying levels of testosterone is also influenced by his genetic makeup, particularly polymorphisms in the androgen receptor, and other upstream signaling and downstream metabolic events, including diabetes mellitus and obesity. Despite decades of research, no compelling evidence exists that increasing testosterone beyond this threshold level has a causative role in prostate cancer, or indeed changes the biology of the disease. Notwithstanding this, the reluctance to utilize testosterone replacement has been

  8. Statin Induced Myopathy a Patient with Multiple Systemic Diseases

    Directory of Open Access Journals (Sweden)

    Özgül Uçar

    2011-04-01

    Full Text Available Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins are the most successful class of drugs for the treatment of hypercholesterolaemia and dyslipidaemia. However, the popular profile of statins in terms of efficacy has been maligned by theiradverse effects. Statin induced myopathy, which can be seen at any time during the course of therapy, is a clinically important cause of statin intolerance and discontinuation. When a patient with multiple systemic diseases who use numerous medications represent with myalgia and muscle cramps, statin induced myopathy may not be remembered at first. We present a patient with multiple systemic diseases, alcohol and morphine abuse in whom myopathy developed. After exclusion of other etiologies, we concluded that myopathy was related to statin therapy.

  9. Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial

    NARCIS (Netherlands)

    Moriarty, Patrick M.; Thompson, Paul D.; Cannon, Christopher P.; Guyton, John R.; Bergeron, Jean; Zieve, Franklin J.; Bruckert, Eric; Jacobson, Terry A.; Kopecky, Stephen L.; Baccara-Dinet, Marie T.; Du, Yunling; Pordy, Robert; Gipe, Daniel A.; Drexel, Heinz; Kaser, Susanne; Toplak, Hermann; Baass, Alexis; Gaudet, Daniel; Farnier, Michel; Krempf, Michel; Moulin, Philippe; Serusclat, Pierre; Cohen, Hofit; Gavish, Dov; Hussein, Osama; Maislos, Maximo; Schurr, Daniel; Arca, Marcello; Averna, Maurizio; Pozzi, Claudio; Balsamo, Cinisello; Heggen, Eli; Langslet, Gisle; Al-Bahrani, Ali; Blagden, Mark; O'Kane, Maurice; Reynolds, Tim; Viljoen, Adie; Andersen, James; Awasty, Vivek; Bayron, Carlos; Bestermann, William; Bolster, Eric; deGoma, Emil; Dunn, Fredrick; Duprez, Daniel; Elam, Marshall; El Shahawy, Mahfouz; Faillace, Robert; Kastelein, John J. P.

    2015-01-01

    BACKGROUND: Statin intolerance limits many patients from achieving optimal low-density lipoprotein cholesterol (LDL-C) concentrations. Current options for such patients include using a lower but tolerated dose of a statin and adding or switching to ezetimibe or other non-statin therapies. METHODS:

  10. Statins and risk of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Richard Tjan

    2015-12-01

    blood glucose of 3 mg/dL as a result of statin use.(3 Here is a verbatim quote from Shah and Goldfine: “For any prescription drug, the potential benefits to health must be balanced against potential risks. Understanding these potential risks can help physicians and patients make informed decisions on whether to use a medication.” Since the risk of statin-induced diabetes mellitus is important and unknown in the population of persons at lower risk of heart disease, it is considered prudent not to prescribe statins, except when diet and exercise cannot achieve LDL goals.(3 The mechanism by which statins induce diabetes in older persons has been recently uncovered. A Canadian research team has shown that statins increase macrophage IL-1 secretion, ndicating activation of the nucleotide-binding and oligomerization domain (NOD-like receptor pyrin domain 3 (NLRP3 inflammasome (caspase-1 inflammasome, which promotes insulin resistance, a precursor of type 2 diabetes. These investigators are of the opinion that the risk of statin-induced insulin Univ Med - Vol. 33 No.2 73 resistance may be reduced by inhibiting the NLRP3/caspase-1 inflammasome, particularly in obese, hyperlipidemic patients who are often at risk for developing diabetes, but have to use statins.(4 In conclusion, although the risk of new diabetes mellitus with statin therapy may be considered to be minimal, the use of statins should only be prescribed by physicians for patients at risk for cardiovascular disease. However, when these patients are also at risk for diabetes mellitus, their blood glucose level should be monitored.(3 On the other hand, since statins may trigger new onset diabetes, presumably in predisposed persons, and since diabetes carries a risk of cardiovascular disease, even statins with the least side effects should not be used routinely for primary prevention, least of all as over-the-counter drugs. Primum non nocere.

  11. Statin use and risk of endometrial cancer

    DEFF Research Database (Denmark)

    Sperling, Cecilie D.; Verdoodt, Freija; Friis, Soren

    2017-01-01

    INTRODUCTION: Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer....... MATERIAL AND METHODS: Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions...... on separate dates. Conditional logistic regressions were used to estimate age-matched (by design) and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CI) for endometrial cancer associated with statin use. The multivariable-adjusted models included parity, hormone replacement therapy...

  12. Potential role of coenzyme Q10 in facilitating recovery from statin-induced rhabdomyolysis.

    Science.gov (United States)

    Wang, L W; Jabbour, A; Hayward, C S; Furlong, T J; Girgis, L; Macdonald, P S; Keogh, A M

    2015-04-01

    Rhabdomyolysis is a rare, but serious complication of statin therapy, and represents the most severe end of the spectrum of statin-induced myotoxicity. We report a case where coenzyme Q10 facilitated recovery from statin-induced rhabdomyolysis and acute renal failure, which had initially persisted despite statin cessation and haemodialysis. This observation is biologically plausible due to the recognised importance of coenzyme Q10 in mitochondrial bioenergetics within myocytes, and the fact that statins inhibit farnesyl pyrophosphate production, a biochemical step crucial for coenzyme Q10 synthesis. Coenzyme Q10 is generally well tolerated, and may potentially benefit patients with statin-induced rhabdomyolysis. © 2015 Royal Australasian College of Physicians.

  13. Clinical role of a fixed combination of standardized Berberis aristata and Silybum marianum extracts in diabetic and hypercholesterolemic patients intolerant to statins

    Directory of Open Access Journals (Sweden)

    Di Pierro F

    2015-02-01

    Full Text Available Francesco Di Pierro,1 Iaele Bellone,2 Giuliana Rapacioli,3 Pietro Putignano4 1Scientific Department, Velleja Research, Milan, Italy; 2ASL TO1, Turin, Italy; 3AIOR, Pontenure, Province of Piacenza, Italy; 4University Hospital San Gerardo, Monza, Italy Background: Statin intolerance is a medical condition often leading patients to nonadherence to the prescribed therapy or to a relevant reduction of the statin dosage. Both situations determine a totally or partially uncontrolled lipid profile, and these conditions unquestionably increase the risk of cardiovascular events. Methods: We enrolled hypercholesterolemic, type 2 diabetic patients complaining of intolerance to statins. Some of them had reduced the statin dose ‘until the disappearance of symptoms’; others had opted for treatment with ezetimibe; and yet others were not undergoing any treatment at all. All patients of the three groups were then given a fixed combination of berberine and silymarin (Berberol®, known from previous papers to be able to control both lipidic and glycemic profiles. Results: The tested product both as a single therapy and as add-on therapy to low-dose statin or to ezetimibe reduced triglycerides, low-density lipoprotein cholesterol, fasting blood glucose, and glycosylated hemoglobin in a significant manner without inducing toxicity conditions that might be somehow ascribed to a statin-intolerant condition. Conclusion: Our study demonstrates that use of Berberol®, administered as a single or add-on therapy in statin-intolerant subjects affected by diabetes and hypercholesterolemia is a safe and effective tool capable of improving the patients' lipidic and glycemic profiles. Keywords: berberine, silymarin, Berberol®, ezetimibe, cholesterol, type 2 diabetes

  14. Rising statin use and effect on ischemic stroke outcome

    Directory of Open Access Journals (Sweden)

    Haymore Joseph

    2004-03-01

    Full Text Available Abstract Background Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome. Methods This was an observational study of 436 patients admitted to the National Institutes of Health Suburban Hospital Stroke Program between July 2000 and December 2002. Self-reported risk factors for stroke were obtained on admission. Stroke severity was determined by the admission National Institutes of Health Stroke Scale score. Good outcome was defined as a Rankin score Results There were 436 patients with a final diagnosis of ischemic stroke; statin data were available for 433 of them. A total of 95/433 (22% of patients were taking a statin when they were admitted, rising from 16% in 2000 to 26% in 2002. Fifty-one percent of patients taking statins had a good outcome compared to 38% of patients not taking statins (p = 0.03. After adjustment for confounding factors, statin pretreatment was associated with a 2.9 odds (95% CI: 1.2–6.7 of a good outcome at the time of hospital discharge. Conclusions The proportion of patients taking statins when they are admitted with stroke is rising rapidly. Statin pretreatment was significantly associated with an improved functional outcome at discharge. This finding could support the early initiation of statin therapy after stroke.

  15. Statins Suppress Ebola Virus Infectivity by Interfering with Glycoprotein Processing.

    Science.gov (United States)

    Shrivastava-Ranjan, Punya; Flint, Mike; Bergeron, Éric; McElroy, Anita K; Chatterjee, Payel; Albariño, César G; Nichol, Stuart T; Spiropoulou, Christina F

    2018-05-01

    Ebola virus (EBOV) infection is a major public health concern due to high fatality rates and limited effective treatments. Statins, widely used cholesterol-lowering drugs, have pleiotropic mechanisms of action and were suggested as potential adjunct therapy for Ebola virus disease (EVD) during the 2013-2016 outbreak in West Africa. Here, we evaluated the antiviral effects of statin (lovastatin) on EBOV infection in vitro Statin treatment decreased infectious EBOV production in primary human monocyte-derived macrophages and in the hepatic cell line Huh7. Statin treatment did not interfere with viral entry, but the viral particles released from treated cells showed reduced infectivity due to inhibition of viral glycoprotein processing, as evidenced by decreased ratios of the mature glycoprotein form to precursor form. Statin-induced inhibition of infectious virus production and glycoprotein processing was reversed by exogenous mevalonate, the rate-limiting product of the cholesterol biosynthesis pathway, but not by low-density lipoprotein. Finally, statin-treated cells produced EBOV particles devoid of the surface glycoproteins required for virus infectivity. Our findings demonstrate that statin treatment inhibits EBOV infection and suggest that the efficacy of statin treatment should be evaluated in appropriate animal models of EVD. IMPORTANCE Treatments targeting Ebola virus disease (EVD) are experimental, expensive, and scarce. Statins are inexpensive generic drugs that have been used for many years for the treatment of hypercholesterolemia and have a favorable safety profile. Here, we show the antiviral effects of statins on infectious Ebola virus (EBOV) production. Our study reveals a novel molecular mechanism in which statin regulates EBOV particle infectivity by preventing glycoprotein processing and incorporation into virus particles. Additionally, statins have anti-inflammatory and immunomodulatory effects. Since inflammation and dysregulation of the immune

  16. Effects of ubiquinone (coenzyme Q10) on myopathy in statin users.

    NARCIS (Netherlands)

    Schaars, C.F.; Stalenhoef, A.F.H.

    2008-01-01

    PURPOSE OF REVIEW: Statins are associated with muscle complaints, including myositis. The mechanism through which statin use causes muscle toxicity is unknown. One of the theories is that statin therapy reduces coenzyme Q10 levels in muscle mitochondria, which leads to muscle injury and myopathy.

  17. Statin treatment and risk of recurrent venous thromboembolism: a nationwide cohort study

    NARCIS (Netherlands)

    Nguyen, Cu Dinh; Andersson, Charlotte; Jensen, Thomas Bo; Gjesing, Anne; Schjerning Olsen, Anne-Marie; Malta Hansen, Carolina; Büller, Harry; Torp-Pedersen, Christian; Gislason, Gunnar H.

    2013-01-01

    Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin therapy and

  18. Individualized Statin Benefit for Determining Statin Eligibility in the Primary Prevention of Cardiovascular Disease.

    Science.gov (United States)

    Thanassoulis, George; Williams, Ken; Altobelli, Kathleen Kimler; Pencina, Michael J; Cannon, Christopher P; Sniderman, Allan D

    2016-04-19

    Current guidelines recommend statins in the primary prevention of cardiovascular disease on the basis of predicted cardiovascular risk without directly considering the expected benefits of statin therapy based on the available randomized, controlled trial evidence. We included 2134 participants representing 71.8 million American residents potentially eligible for statins in primary prevention from the National Health and Nutrition Examination Survey for the years 2005 to 2010. We compared statin eligibilities using 2 separate approaches: a 10-year risk-based approach (≥7.5% 10-year risk) and an individualized benefit approach (ie, based on predicted absolute risk reduction over 10 years [ARR10] ≥2.3% from randomized, controlled trial data). A risk-based approach led to the eligibility of 15.0 million (95% confidence interval, 12.7-17.3 million) Americans, whereas a benefit-based approach identified 24.6 million (95% confidence interval, 21.0-28.1 million). The corresponding numbers needed to treat over 10 years were 21 (range, 9-44) and 25 (range, 9-44). The benefit-based approach identified 9.5 million lower-risk (statin treatment who had the same or greater expected benefit from statins (≥2.3% ARR10) compared with higher-risk individuals. This lower-risk/acceptable-benefit group includes younger individuals (mean age, 55.2 versus 62.5 years; PStatin treatment in this group would be expected to prevent an additional 266 508 cardiovascular events over 10 years. An individualized statin benefit approach can identify lower-risk individuals who have equal or greater expected benefit from statins in primary prevention compared with higher-risk individuals. This approach may help develop guideline recommendations that better identify individuals who meaningfully benefit from statin therapy. © 2016 American Heart Association, Inc.

  19. Postoperative atrial fibrillation in patients on statins undergoing ...

    African Journals Online (AJOL)

    Introduction: The efficacy of perioperative statin therapy in decreasing postoperative morbidity in patients undergoing valve replacements and repairs is unknown. The aim of our study was to determine whether or not the literature supports the hypothesis that statins decrease postoperative atrial fibrillation (AF), and hence ...

  20. Statin non-adherence and residual cardiovascular risk: There is need for substantial improvement.

    Science.gov (United States)

    Banach, Maciej; Stulc, Tomas; Dent, Ricardo; Toth, Peter P

    2016-12-15

    Although statin therapy has proven to be the cornerstone for prevention and treatment of cardiovascular disease (CVD), there are many patients for whom long-term therapy remains suboptimal. The aims of this article are to review the current complex issues associated with statin use and to explore when novel treatment approaches should be considered. Statin discontinuation as well as adherence to statin therapy remain two of the greatest challenges for lipidologists. Evidence suggests that between 40 and 75% of patients discontinue their statin therapy within one year after initiation. Furthermore, whilst the reasons for persistence with statin therapy are complex, evidence shows that low-adherence to statins negatively impacts clinical outcomes and residual CV risk remains a major concern. Non-adherence or lack of persistence with long-term statin therapy in real-life may be the main cause of inadequate low density lipoprotein cholesterol lowering with statins. There is a large need for the improvement of the use of statins, which have good safety profiles and are inexpensive. On the other hand, in a non-cost-constrained environment, proprotein convertase subtilisin/kexin type 9 inhibitors should arguably be used more often in those patients in whom treatment with statins remains unsatisfactory. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. INTEGRATED ASSESSMENT OF STATIN-ASSOCIATED MUSCLE DAMAGE PREDICTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

    OpenAIRE

    V. I. Petrov; O. N. Smuseva; Yu. V. Solovkina

    2013-01-01

    Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months,...

  2. Hormone therapy in transgender adults is safe with provider supervision; A review of hormone therapy sequelae for transgender individuals

    OpenAIRE

    Weinand, Jamie D.; Safer, Joshua D.

    2015-01-01

    Introduction: Some providers report concern for the safety of transgender hormone therapy (HT). Methods: This is a systematic literature review of HT safety for transgender adults. Results: Current literature suggests HT is safe when followed carefully for certain risks. The greatest health concern for HT in transgender women is venous thromboembolism. HT among transgender men appears to cause polycythemia. Both groups experienced elevated fasting glucose. There is no increase in cancer...

  3. Efficacy and Safety of Alirocumab 150 mg Every 4 Weeks in Patients With Hypercholesterolemia Not on Statin Therapy

    DEFF Research Database (Denmark)

    Stroes, Erik; Guyton, John R; Lepor, Norman

    2016-01-01

    controlled hypercholesterolemia and not on statin (majority with statin-associated muscle symptoms), receiving treatment with fenofibrate, ezetimibe, or diet alone. METHODS AND RESULTS: Patients were randomly assigned to placebo, alirocumab 150 mg Q4W or 75 mg Q2W (calibrator arm), with dose adjustment......: Alirocumab 150 mg Q4W can be considered in patients not on statin with inadequately controlled hypercholesterolemia as a convenient option for lowering LDL-C. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02023879....

  4. Statins and Cancer Prevention

    Science.gov (United States)

    ... opposed to the use of another type of lipid-lowering drug, fibrates). [Statins and the risk of colorectal cancer. Poynter, JN., et al. New England Journal of Medicine , May 26, 2005, (352:2184–92]. Is NCI supporting research with statins to prevent other types of cancer? ...

  5. Statin resistance and export

    DEFF Research Database (Denmark)

    2015-01-01

    The present invention relates e.g. to methods of producing statins in transgenic, non-filamentous microorganisms such as Saccharomyces cerevisiae. In addition, the present invention relates to the transgenic, non-filamentous microorganisms as such as well as various uses of transmembrane statin e...

  6. Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery

    Science.gov (United States)

    Sato, Hiroaki; Carvalho, George; Sato, Tamaki; Hatzakorzian, Roupen; Lattermann, Ralph; Codere-Maruyama, Takumi; Matsukawa, Takashi; Schricker, Thomas

    2012-01-01

    OBJECTIVE Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting. RESEARCH DESIGN AND METHODS In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis. RESULTS We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P statin group (SD, P statin use was independently associated with intraoperative insulin sensitivity (β = −0.16; P = 0.03). CONCLUSIONS Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients. PMID:22829524

  7. Prevention and management of statin adverse effects: A practical approach for pharmacists.

    Science.gov (United States)

    Barry, Arden R; Beach, Jessica E; Pearson, Glen J

    2018-01-01

    Statin-associated adverse effects, primarily muscle-related symptoms, occur in up to approximately one-third of patients in clinical practice. Recently, a Canadian Consensus Working Group outlined 6 key principles to assess and manage patients with goal-inhibiting statin intolerance, defined as a syndrome characterized by symptoms or biomarker abnormalities that prevent the long-term use of and adherence to indicated statin therapy, which includes a trial of at least 2 statins and precludes reversible causes of statin adverse effects. These principles ensure patients are appropriately receiving a statin and aware of both the benefits and risks of therapy. As well, they address factors that may increase the risk of statin-associated myopathy. A thorough assessment of patients' clinical and laboratory history should be performed in any patient presenting with muscle symptoms on statin therapy, followed by a systematic dechallenge/rechallenge approach. In practice, most patients with statin intolerance due to muscle symptoms will be able to tolerate another statin. This is of particular importance because of the relative paucity of compelling evidence demonstrating a cardiovascular benefit with nonstatin therapies. Pharmacists are ideally situated to provide patient education, recommend changes to therapy and monitor patients with goal-inhibiting statin intolerance.

  8. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial.

    Science.gov (United States)

    Ridker, Paul M; Genest, Jacques; Boekholdt, S Matthijs; Libby, Peter; Gotto, Antonio M; Nordestgaard, Børge G; Mora, Samia; MacFadyen, Jean G; Glynn, Robert J; Kastelein, John J P

    2010-07-31

    for apolipoprotein A1 showed an equivalent strong relation to frequency of primary outcomes in the placebo group but little association in the rosuvastatin group. Although measurement of HDL-cholesterol concentration is useful as part of initial cardiovascular risk assessment, HDL-cholesterol concentrations are not predictive of residual vascular risk among patients treated with potent statin therapy who attain very low concentrations of LDL cholesterol. AstraZeneca. Copyright 2010 Elsevier Ltd. All rights reserved.

  9. Adaptation to statins restricts human tumour growth in Nude mice

    International Nuclear Information System (INIS)

    Follet, Julie; Rémy, Lionel; Hesry, Vincent; Simon, Brigitte; Gillet, Danièle; Auvray, Pierrick; Corcos, Laurent; Le Jossic-Corcos, Catherine

    2011-01-01

    Statins have long been used as anti-hypercholesterolemia drugs, but numerous lines of evidence suggest that they may also bear anti-tumour potential. We have recently demonstrated that it was possible to isolate cancer cells adapted to growth in the continuous presence of lovastatin. These cells grew more slowly than the statin-sensitive cells of origin. In the present study, we compared the ability of both statin-sensitive and statin-resistant cells to give rise to tumours in Nude mice. HGT-1 human gastric cancer cells and L50 statin-resistant derivatives were injected subcutaneously into Nude mice and tumour growth was recorded. At the end of the experiment, tumours were recovered and marker proteins were analyzed by western blotting, RT-PCR and immunohistochemistry. L50 tumours grew more slowly, showed a strong decrease in cyclin B1, over-expressed collagen IV, and had reduced laminin 332, VEGF and CD34 levels, which, collectively, may have restricted cell division, cell adhesion and neoangiogenesis. Taken together, these results showed that statin-resistant cells developed into smaller tumours than statin-sensitive cells. This may be reflective of the cancer restricting activity of statins in humans, as suggested from several retrospective studies with subjects undergoing statin therapy for several years

  10. Creating a Safe Place in the Midst of Aggression: Music Therapy in Child Psychiatry

    Directory of Open Access Journals (Sweden)

    Marieke Degryse

    2010-01-01

    Full Text Available Working as a music therapist in a psychiatric unit for children with learning disabilities, one is often confronted with a lot of aggression. Most of these children have attachment disorders and severe behavioural problems. By which means can music exist in music therapy within this specific setting? Can we speak of a traumatic nature in music and body? This article will present a case study, where finding a safe place within music therapy is of major importance. Learning and listening to songs can be a necessary way to safeguard control for the client, gain some self-confidence, and create a place for regression. Going through this process in finding a safe and contained place within music therapy, the possibility of playing techniques arises, offering the freedom for exploration and a form of control and predictability. The case study concludes with the importance of playfulness whereby traumatic material can be digested through the music. Also, the role of singing songs in music therapy with this population is highlighted briefly.

  11. Is exercise training safe and beneficial in patients receiving left ventricular assist device therapy?

    Science.gov (United States)

    Alsara, Osama; Perez-Terzic, Carmen; Squires, Ray W; Dandamudi, Sanjay; Miranda, William R; Park, Soon J; Thomas, Randal J

    2014-01-01

    Because a limited number of patients receive heart transplantation, alternative therapies, such as left ventricular assist device (LVAD) therapy, have emerged. Published studies have shown that LVAD implantation, by itself, improves exercise tolerance to the point where it is comparable to those with mild heart failure. The improvement in exercise capacity is maximally achieved 12 weeks after LVAD therapy and can continue even after explantation of the device. This effect varies, depending on the type of LVAD and exercise training. The available data in the literature on safety and benefits of exercise training in patients after LVAD implantation are limited, but the data that are available suggest that training trends to be safe and have an impact on exercise capacity in LVAD patients. Although no studies were identified on the role of cardiac rehabilitation programs in the management of LVAD patients, it appears that cardiac rehabilitation programs offer an ideal setting for the provision of supervised exercise training in this patient group.

  12. [Side effects of the HMG-CoA reductase inhibitors (statins). Lupus erythematosus induced by Atorvastatin therapy].

    Science.gov (United States)

    Hydzik, Piotr; Szpak, Dorota

    2011-01-01

    The paper describes the case of 56 years old woman admitted to the Toxicology Department because of skin lesions, joint and muscle pain and elevated activity of transaminases and creatine phosfokinase as well in biochemical analysis. The symptoms occurred after 6 days of the Atorvastatin therapy. The clinical picture indicated side effects of the hipolipemic therapy, but the presence of the skin lesions suggested drug induced collagenosis (lupus erythrematosus, dermatomyositis). Immunological studies confirmed association with antinuclear antibodies (ANA) and anti-Mi-2 autoantibodies in the serum. Immunosuppressive therapy was ordered with clinical and biochemical improvement.

  13. Statin use and risk for type 2 diabetes: what clinicians should know.

    Science.gov (United States)

    Maki, Kevin C; Diwadkar-Navsariwala, Veda; Kramer, Melvyn W

    2018-03-01

    Statins are the first line of pharmacologic treatment for the management of hypercholesterolemia in patients at risk for atherosclerotic cardiovascular (CV) disease. In recent years, several randomized, controlled trials (RCTs) and observational studies have reported increased risk for new-onset type 2 diabetes mellitus (T2D) with statin treatment, particularly with use of high-intensity statins that reduce low-density lipoprotein cholesterol (LDL-C) by 50% or more. This paper summarizes the data from RCTs and observational studies for statin-associated T2D risk, and puts into perspective this evidence, weighed against the established benefits of statin therapy for CV risk reduction. In RCTs, the increase in T2D risk with statin therapy appears to be attributable mainly to those with major T2D risk factors. The increase in incidence of T2D in those with major risk is approximately 25% for statin use, compared to placebo, and for intensive statin therapy compared to moderate-intensity statin therapy. However, in those with major T2D risk factors, the number of CV disease events prevented for each excess case of T2D is close to or greater than one, indicating that the risk-benefit ratio still strongly favors use of statin therapy, or intensive statin therapy, for patients with sufficient CV disease risk to warrant cholesterol-lowering drug therapy. Recommendations are summarized for evaluation of the T2D risk factor profile before initiation of and during statin therapy. In addition, the importance of lifestyle management and other preventive measures is emphasized for management of risks for both T2D and CV disease events in patients receiving statin therapy.

  14. [Radioiodine 131I therapy of hyperthyroidism on an outpatient basis - safe, effective and economic option].

    Science.gov (United States)

    Jiskra, J; Kubinyi, J; Telička, Z

    2012-02-01

    Radioiodine 131I therapy of hyperthyroidism on an outpatient basis is widely accepted over the world. In Czech Republic, however, radioiodine therapy is still not enough used, and has been realized on an inpatient basis to date. Our work is the first analysis of the experiences with radioiodine therapy of hyperthyroidism on an outpatient basis in Czech Republic. Capsule with 550 MBq of 131I was administered orally in 39 hyperthyroid patients (32 women and 8 men, 21 with autoimmune Graves hyperthyroidism and 18 with toxic thyroid nodules, mean age 66.8 years). In 32 of them we evaluated effectiveness and complications of therapy after 12-42 months. We also compared financial costs of the radioiodine treatment on an outpatient basis with the treatment in hospitalization and with surgery. After the treatment, 9/32 (28 %) patients were euthyroid without thyrostatic/thyroxine treatment, 18/32 (60 %) patients were hypothyroid with thyroxine therapy, 2/32 (6 %) patients significantly decreased doses of thyrostatic drugs. In 2/32 (6 %) patients the treatment was ineffective. The effect of the treatment did not depend on the etiology and severity of hyperthyroidism, but decreased with thyroid volume. Patients with ineffective or only partially effective treatment had median of thyroid volume more than 40 ml. In 1 patient thyroid associated ophthalmopathy was moderately worsened. Other complications were not observed. If we compared financial costs in model with 1 patient, we found that the costs of radioiodine therapy on an outpatient basis (118.7 €) comprise only 16 % of the costs of radioiodine therapy in hospitalization (728 €) and only 25 % of the costs of surgery (475.6 €). Radioiodine 131I is effective and safe in the treatment of hyperthyroidism and the therapy on an outpatient basis is much cheaper choice. The therapy with 131I on an outpatient basis is not suitable in patients with thyroid volume more than 40 ml.

  15. Statins and perioperative myocardial infarction. | Levin | Southern ...

    African Journals Online (AJOL)

    The growing prevalence of atherosclerosis means that perioperative myocardial infarction (PMI) is of significant concern to anesthesiologists. Perioperative revascularization (if indicated medically), beta blockade (in high risk patients) and statin therapy are therapeutic modalities that are currently employed to reduce PMI.

  16. The OPTIMIZE trial: Rationale and design of a randomized controlled trial of motivational enhancement therapy to improve adherence to statin medication.

    Science.gov (United States)

    Rash, Joshua A; Lavoie, Kim L; Sigal, Ronald J; Campbell, David J T; Manns, Braden J; Tonelli, Marcello; Campbell, Tavis S

    2016-07-01

    Statins are a class of medications that are particularly effective for lowering cholesterol and reducing cardiovascular morbidity and mortality. Despite a range of benefits, non-adherence to statin medication is prevalent with 50% to 75% of patients failing to adhere to treatment within the first 2-years. A previous review on interventions to improve adherence to cholesterol lowering medication concluded that rigorous trials were needed with emphasis on the patient's perspective and shared decision making. Motivational interviewing (MInt) is a promising patient-centered approach for improving adherence in patients with chronic diseases. This manuscript describes the rational and design of a randomized controlled trial (RCT) testing the efficacy of MInt in improving adherence to statin medication. Patients filling their first statin prescription will be recruited to complete a 6-month observation run-in period (phase-1) after which medication possession ratio (MPR) will be assessed. Patients meeting criteria for non-adherence (MPR≤60%) will be invited to participate in the trial. 336 non-adherent new statin users will undergo a fasting lipid panel, complete baseline questionnaires, and be randomly allocated to receive four sessions of adherence education delivered using MInt (EdMInt) or to an education control (EC) delivered at 3-month intervals. Final assessments will occur 12-months after the first EdMInt or EC session. The primary outcome is change in MPR adherence to statin medication from baseline to 12-months. Secondary outcomes include within-patient change in self-reported medication adherence, stage of change and self-efficacy for medication adherence, motivation to adhere to statin medication, and lipid profile. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge.

    Directory of Open Access Journals (Sweden)

    Marshall B Elam

    Full Text Available Statins, the 3-hydroxy-3-methyl-glutaryl (HMG-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs. To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin myalgia, we subjected DEGs to Ingenuity Pathways (IPA and DAVID (Database for Annotation, Visualization and Integrated Discovery analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51; activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1; protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras. Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single

  18. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge.

    Science.gov (United States)

    Elam, Marshall B; Majumdar, Gipsy; Mozhui, Khyobeni; Gerling, Ivan C; Vera, Santiago R; Fish-Trotter, Hannah; Williams, Robert W; Childress, Richard D; Raghow, Rajendra

    2017-01-01

    Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin myalgia, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single nucleotide

  19. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge

    Science.gov (United States)

    Majumdar, Gipsy; Mozhui, Khyobeni; Gerling, Ivan C.; Vera, Santiago R.; Fish-Trotter, Hannah; Williams, Robert W.; Childress, Richard D.

    2017-01-01

    Statins, the 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase inhibitors, are widely prescribed for treatment of hypercholesterolemia. Although statins are generally well tolerated, up to ten percent of statin-treated patients experience myalgia symptoms, defined as muscle pain without elevated creatinine phosphokinase (CPK) levels. Myalgia is the most frequent reason for discontinuation of statin therapy. The mechanisms underlying statin myalgia are not clearly understood. To elucidate changes in gene expression associated with statin myalgia, we compared profiles of gene expression in skeletal muscle biopsies from patients with statin myalgia who were undergoing statin re-challenge (cases) versus those of statin-tolerant controls. A robust separation of case and control cohorts was revealed by Principal Component Analysis of differentially expressed genes (DEGs). To identify putative gene expression and metabolic pathways that may be perturbed in skeletal muscles of patients with statin myalgia, we subjected DEGs to Ingenuity Pathways (IPA) and DAVID (Database for Annotation, Visualization and Integrated Discovery) analyses. The most prominent pathways altered by statins included cellular stress, apoptosis, cell senescence and DNA repair (TP53, BARD1, Mre11 and RAD51); activation of pro-inflammatory immune response (CXCL12, CST5, POU2F1); protein catabolism, cholesterol biosynthesis, protein prenylation and RAS-GTPase activation (FDFT1, LSS, TP53, UBD, ATF2, H-ras). Based on these data we tentatively conclude that persistent myalgia in response to statins may emanate from cellular stress underpinned by mechanisms of post-inflammatory repair and regeneration. We also posit that this subset of individuals is genetically predisposed to eliciting altered statin metabolism and/or increased end-organ susceptibility that lead to a range of statin-induced myopathies. This mechanistic scenario is further bolstered by the discovery that a number of single nucleotide

  20. Cost-effectiveness of increasing statin adherence for primary and secondary prevention in community pharmacies

    NARCIS (Netherlands)

    Vegter, S.; Oosterhof, P.; Van Boven, J.F.; Stuurman-Bieze, A.G.G.; Hiddink, E.G.; Postma, M.J.

    2013-01-01

    Objectives: Therapy persistence is important to achieve optimal clinical benefits of statin therapy. The aim of this study was to determine the cost-effectiveness of pharmaceutical care in community pharmacies, aimed to increase persistence with statin therapy for both primary and secondary

  1. Maximal safe dose therapy of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Lee, Jong Jin; Seok, Ju Won; Uh, Jae Sun

    2005-01-01

    In patients with recurrent or metastatic differentiated thyroid carcinoma, residual disease despite repetitive fixed dose I-131 therapy presents an awkward situation in terms of treatment decision making. Maximal safe dose (MSD) administration base on bone marrow radiation allows the delivery of a large amount I-131 to thyroid cancer tissue within the safety margin. We investigated the efficacy of MSD in differentiated thyroid cancers, which had persisted after conventional fixed dose therapy. Forty-six patients with differentiated thyroid carcinoma who had non-responsible residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. The postoperative pathology consisted of 43 papillary carcinomas and 3 follicular carcinomas. MSD was calculated according the Memorial Sloan Kettering Cancer Center protocol using blood samples. MSDs were administered at intervals of at least 6 months. Treatment responses were evaluated using I-131 whole body scan (WBS) and serum thyroglobulin measurements. Mean calculated MSD was 12.5±2.1 GBq. Of the 46 patients, 6 (13.0%) showed complete remission, 15 (32.6%) partial response, 19 (41.3%) stable disease, and 6 (13.0%) disease progression. Thus, about a half of the patients showed complete or partial remission, and of these patients, 14 (67%) showed response after a single MSD administration and 6 (29%) showed response after the second dose of MSD administrations. Twenty-nine patients (63%) experienced transient cytopenia after therapy, and recovered spontaneously with the exception of one. MSD administration is an effective method even in the patients who failed to be treated by conventional fixed dose therapy. MSD therapy of I-131 can be considered in the patients who failed by fixed dose therapy

  2. Controlling Cholesterol with Statins

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

  3. Statins: pros and cons.

    Science.gov (United States)

    Pinal-Fernandez, Iago; Casal-Dominguez, Maria; Mammen, Andrew L

    2018-05-23

    Statins inhibit the critical step of cholesterol synthesis in which 3-hydroxy-3-methylglutaryl coenzyme A (HMGC) is transformed to mevalonate by the enzyme HMGC reductase. By doing so, they have a potent lipid-lowering effect that reduces cardiovascular risk and decreases mortality. Since the mevalonate pathway also influences endothelial function, the inflammatory response, and coagulation, the effects of statins reach well beyond their cholesterol lowering properties. As with all drugs, statins may have adverse effects; these include musculoskeletal symptoms, increased risk of diabetes, and higher rates of hemorrhagic stroke. However, the frequency of adverse effects is extremely low and, in selected patient populations, the benefits of statins considerably outweigh the potential risks. Published by Elsevier España, S.L.U.

  4. Efficacy, safety and tolerability of ongoing statin plus ezetimibe versus doubling the ongoing statin dose in hypercholesterolemic Taiwanese patients: an open-label, randomized clinical trial

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

    Full Text Available Abstract Background Reducing low-density lipoprotein cholesterol (LDL-C is associated with reduced risk for major coronary events. Despite statin efficacy, a considerable proportion of statin-treated hypercholesterolemic patients fail to reach therapeutic LDL-C targets as defined by guidelines. This study compared the efficacy of ezetimibe added to ongoing statins with doubling the dose of ongoing statin in a population of Taiwanese patients with hypercholesterolemia. Methods This was a randomized, open-label, parallel-group comparison study of ezetimibe 10 mg added to ongoing statin compared with doubling the dose of ongoing statin. Adult Taiwanese hypercholesterolemic patients not at optimal LDL-C levels with previous statin treatment were randomized (N = 83 to ongoing statin + ezetimibe (simvastatin, atorvastatin or pravastatin + ezetimibe at doses of 20/10, 10/10 or 20/10 mg or doubling the dose of ongoing statin (simvastatin 40 mg, atorvastatin 20 mg or pravastatin 40 mg for 8 weeks. Percent change in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C and triglycerides, and specified safety parameters were assessed at 4 and 8 weeks. Results At 8 weeks, patients treated with statin + ezetimibe experienced significantly greater reductions compared with doubling the statin dose in LDL-C (26.2% vs 17.9%, p = 0.0026 and total cholesterol (20.8% vs 12.2%, p = 0.0003. Percentage of patients achieving treatment goal was greater for statin + ezetimibe (58.6% vs doubling statin (41.2%, but the difference was not statistically significant (p = 0.1675. The safety and tolerability profiles were similar between treatments. Conclusion Ezetimibe added to ongoing statin therapy resulted in significantly greater lipid-lowering compared with doubling the dose of statin in Taiwanese patients with hypercholesterolemia. Studies to assess clinical outcome benefit are ongoing. Trial registration Registered at ClinicalTrials.gov: NCT00652327

  5. Cholesterol treatment with statins: Who is left out and who makes it to goal?

    Directory of Open Access Journals (Sweden)

    Winters Paul

    2010-03-01

    Full Text Available Abstract Background Whether patient socio-demographic characteristics (age, sex, race/ethnicity, income, and education are independently associated with failure to receive indicated statin therapy and/or to achieve low density lipoprotein cholesterol (LDL-C therapy goals are not known. We examined socio-demographic factors associated with a eligibility for statin therapy among those not on statins, and b achievement of statin therapy goals. Methods Adults (21-79 years participating in the United States (US National Health and Nutrition Examination Surveys, 1999-2006 were studied. Statin eligibility and achievement of target LDL-C was assessed using the US Third Adult Treatment Panel (ATP III on Treatment of High Cholesterol guidelines. Results Among 6,043 participants not taking statins, 10.4% were eligible. Adjusted predictors of statin eligibility among statin non-users were being older, male, poorer, and less educated. Hispanics were less likely to be eligible but not using statins, an effect that became non-significant with adjustment for language usually spoken at home. Among 537 persons taking statins, 81% were at LDL-C goal. Adjusted predictors of goal failure among statin users were being male and poorer. These risks were not attenuated by adjustment for healthcare access or utilization. Conclusion Among person's not taking statins, the socio-economically disadvantaged are more likely to be eligible and among those on statins, the socio-economically disadvantaged are less likely to achieve statin treatment goals. Further study is needed to identify specific amenable patient and/or physician factors that contribute to these disparities.

  6. Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector

    Directory of Open Access Journals (Sweden)

    Swati Singh

    2017-03-01

    Full Text Available Wiskott-Aldrich syndrome (WAS is a life-threatening immunodeficiency caused by mutations within the WAS gene. Viral gene therapy to restore WAS protein (WASp expression in hematopoietic cells of patients with WAS has the potential to improve outcomes relative to the current standard of care, allogeneic bone marrow transplantation. However, the development of viral vectors that are both safe and effective has been problematic. While use of viral transcriptional promoters may increase the risk of insertional mutagenesis, cellular promoters may not achieve WASp expression levels necessary for optimal therapeutic effect. Here we evaluate a self-inactivating (SIN lentiviral vector combining a chromatin insulator upstream of a viral MND (MPSV LTR, NCR deleted, dl587 PBS promoter driving WASp expression. Used as a gene therapeutic in Was−/− mice, this vector resulted in stable WASp+ cells in all hematopoietic lineages and rescue of T and B cell defects with a low number of viral integrations per cell, without evidence of insertional mutagenesis in serial bone marrow transplants. In a gene transfer experiment in non-human primates, the insulated MND promoter (driving GFP expression demonstrated long-term polyclonal engraftment of GFP+ cells. These observations demonstrate that the insulated MND promoter safely and efficiently reconstitutes clinically effective WASp expression and should be considered for future WAS therapy.

  7. Statin Lactonization by Uridine 5'-Diphospho-glucuronosyltransferases (UGTs).

    Science.gov (United States)

    Schirris, Tom J J; Ritschel, Tina; Bilos, Albert; Smeitink, Jan A M; Russel, Frans G M

    2015-11-02

    Statins are cholesterol-lowering drugs that have proven to be effective in lowering the risk of major cardiovascular events. Although well tolerated, statin-induced myopathies are the most common side effects. Compared to their pharmacologically active acid form, statin lactones are more potent inducers of toxicity. They can be formed by glucuronidation mediated by uridine 5'-diphospho-glucuronosyltransferases (UGTs), but a systematic characterization of subtype specificity and kinetics of lactonization is lacking. Here, we demonstrate for six clinically relevant statins that only UGT1A1, 1A3, and 2B7 contribute significantly to their lactonization. UGT1A3 appeared to have the highest lactonization capacity with marked differences in statin conversion rates: pitavastatin ≫ atorvastatin > cerivastatin > lovastatin > rosuvastatin (simvastatin not converted). Using in silico modeling we could identify a probable statin interaction region in the UGT binding pocket. Polymorphisms in these regions of UGT1A1, 1A3, and 2B7 may be a contributing factor in statin-induced myopathies, which could be used in personalization of statin therapy with improved safety.

  8. [Intratympanic injection therapy for therapy refractory acute hearing loss: A safe option for secondary treatment].

    Science.gov (United States)

    Mühlmeier, G; Maier, S; Maier, M; Maier, H

    2015-10-01

    High-dose corticosteroids are currently recommended for idiopathic sudden sensorineural hearing loss (ISSNHL) treatment. Intratympanic injections (ITI) are of growing importance, especially in cases of therapy resistance. The selection of patients for this procedure in SSNHL has not been adequately examined so far. A total of 77 patients with ISSNHL after ineffective systemic pretreatment underwent intratympanic administration of dexamethasone and hyaluronic acid. Improvement after treatment was determined by pure tone audiometry for both ears before and of the treated ear after ITI. In this study 34 female and 43 male patients with mean age of 57 years showed a pre-ITI hearing loss of 35 dB in the lower frequencies and 69 dB in the higher frequencies. The mean hearing gain was 10 dB and the response rate was 62%. Absolute hearing gain revealed significant improvements at 500 Hz, 1 kHz and 2 kHz. Under inclusion of contralateral thresholds there were hardly any differences up to 4 kHz. In a detailed analysis of responders moderate improvements could be observed even in higher frequencies. Overall, no relevant adverse events occurred. Treatment of ISSNHL resistant to systemic regimens by ITI of steroids provides an option that offers additional prospects of auditory improvement for affected patients. The presented results indicate that these modalities are also valid for patients with pancochlear ISSNHL.

  9. [Statin associated myopathy in clinical practice. Results of DAMA study].

    Science.gov (United States)

    Millán, Jesús; Pedro-Botet, Juan; Climent, Elisenda; Millán, Joaquín; Rius, Joan

    Muscle symptoms, with or without elevation of creatin kinase are one of the main adverse effects of statin therapy, a fact that sometimes limits their use. The aim of this study was to evaluate the clinical characteristics of patients treated with statins who have complained muscle symptoms and to identify possible predictive factors. A cross-sectional one-visit, non-interventional, national multicenter study including patients of both sexes over 18 years of age referred for past or present muscle symptoms associated with statin therapy was conducted. 3,845 patients were recruited from a one-day record from 2,001 physicians. Myalgia was present in 78.2% of patients included in the study, myositis in 19.3%, and rhabdomyolysis in 2.5%. Patients reported muscle pain in 77.5% of statin-treated individuals, general weakness 42.7%, and cramps 28.1%. Kidney failure, intense physical exercise, alcohol consumption (>30g/d in men and 20g/d in women) and abdominal obesity were the clinical situations associated with statin myopathy. Myalgia followed by myositis are the most frequent statin-related side effects. It should be recommended control environmental factors such as intense exercise and alcohol intake as well as abdominal obesity and renal function of the patient treated with statins. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

    Science.gov (United States)

    Stroes, Erik S.; Thompson, Paul D.; Corsini, Alberto; Vladutiu, Georgirene D.; Raal, Frederick J.; Ray, Kausik K.; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G.; Bruckert, Eric; De Backer, Guy; Krauss, Ronald M.; Laufs, Ulrich; Santos, Raul D.; Hegele, Robert A.; Hovingh, G. Kees; Leiter, Lawrence A.; Mach, Francois; März, Winfried; Newman, Connie B.; Wiklund, Olov; Jacobson, Terry A.; Catapano, Alberico L.; Chapman, M. John; Ginsberg, Henry N.; Stroes, Erik; Thompson, Paul D.; Corsini, Alberto; Vladutiu, Georgirene D.; Raal, Frederick J.; Ray, Kausik K.; Roden, Michael; Stein, Evan; Tokgözoğlu, Lale; Nordestgaard, Børge G.; Bruckert, Eric; Krauss, Ronald M.; Laufs, Ulrich; Santos, Raul D.; März, Winfried; Newman, Connie B.; John Chapman, M.; Ginsberg, Henry N.; John Chapman, M.; Ginsberg, Henry N.; de Backer, Guy; Catapano, Alberico L.; Hegele, Robert A.; Kees Hovingh, G.; Jacobson, Terry A.; Leiter, Lawrence; Mach, Francois; Wiklund, Olov

    2015-01-01

    Statin-associated muscle symptoms (SAMS) are one of the principal reasons for statin non-adherence and/or discontinuation, contributing to adverse cardiovascular outcomes. This European Atherosclerosis Society (EAS) Consensus Panel overviews current understanding of the pathophysiology of statin-associated myopathy, and provides guidance for diagnosis and management of SAMS. Statin-associated myopathy, with significant elevation of serum creatine kinase (CK), is a rare but serious side effect of statins, affecting 1 per 1000 to 1 per 10 000 people on standard statin doses. Statin-associated muscle symptoms cover a broader range of clinical presentations, usually with normal or minimally elevated CK levels, with a prevalence of 7–29% in registries and observational studies. Preclinical studies show that statins decrease mitochondrial function, attenuate energy production, and alter muscle protein degradation, thereby providing a potential link between statins and muscle symptoms; controlled mechanistic and genetic studies in humans are necessary to further understanding. The Panel proposes to identify SAMS by symptoms typical of statin myalgia (i.e. muscle pain or aching) and their temporal association with discontinuation and response to repetitive statin re-challenge. In people with SAMS, the Panel recommends the use of a maximally tolerated statin dose combined with non-statin lipid-lowering therapies to attain recommended low-density lipoprotein cholesterol targets. The Panel recommends a structured work-up to identify individuals with clinically relevant SAMS generally to at least three different statins, so that they can be offered therapeutic regimens to satisfactorily address their cardiovascular risk. Further research into the underlying pathophysiological mechanisms may offer future therapeutic potential. PMID:25694464

  11. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial

    NARCIS (Netherlands)

    Ridker, Paul M.; Genest, Jacques; Boekholdt, S. Matthijs; Libby, Peter; Gotto, Antonio M.; Nordestgaard, Børge G.; Mora, Samia; Macfadyen, Jean G.; Glynn, Robert J.; Kastelein, John Jp

    2010-01-01

    Background HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment. Methods

  12. Pleiotropic effects of statins

    Directory of Open Access Journals (Sweden)

    Narasaraju Kavalipati

    2015-01-01

    Full Text Available Statins or 3-hydroxy-methylglutaryl coenzyme A (HMG CoA reductase inhibitors not only prevents the synthesis of cholesterol biosynthesis but also inhibits the synthesis of essential isoprenoid intermediates such as farnesyl pyrophosphate, geranylgeranyl pyrophosphate, isopentanyl adenosine, dolichols and polyisoprenoid side chains of ubiquinone, heme A, and nuclear lamins. These isoprenoid intermediates are required for activation of various intracellular/signaling proteins- small guanosine triphosphate bound protein Ras and Ras-like proteins like Rho, Rab, Rac, Ral, or Rap which plays an indispensible role in multiple cellular processes. Reduction of circulating isoprenoids intermediates as a result of HMG CoA reductase inhibition by statins prevents activation of these signalling proteins. Hence, the multiple effects of statins such as antiinflammatory effects, antioxidant effects, antiproliferative and immunomodulatory effects, plaque stability, normalization of sympathetic outflow, and prevention of platelet aggregation are due to reduction of circulating isoprenoids and hence inactivation of signalling proteins. These multiple lipid-independent effects of statins termed as statin pleiotropy would potentially open floodgates for research in multiple treatment domains catching attentions of researchers and clinician across the globe.

  13. The use of statins in primary prevention

    Directory of Open Access Journals (Sweden)

    Stürzlinger, Heidi

    2006-04-01

    including all relevant parameters has to be done. Moreover - from the economic as well as from the ethic point of view - one of the most important issues in primary prevention therapy is the question of compliance. The amount of risk reduction seen in primary prevention studies can be achieved only if patients as well as doctors follow therapeutic instructions and medical guidelines (as for example the guidelines of the "Adult Treatment Panel III", the "European guidelines on cardiovascular disease prevention in clinical practice" or the guidelines of the German Association of Cardiology and of the "Arzneimittelkommission der deutschen Ärzteschaft für Koronare Herzkrankheit". Conclusion: For (primary prevention of cardiovascular diseases the use of statins as suggested in guidelines is recommended - provided that these guidelines are scientifically evaluated at regular intervals. Regarding stroke, osteoporosis and Alzheimer's disease definite conclusions cannot be drawn at present. Particular attention has to be paid to the problem of compliance both in statin-therapy as well as in alternative therapies. The cost-effectiveness of primary prevention with statins mainly depends on the development of statin prices.

  14. Statin Exposure Is Associated with Decreased Asthma-related Emergency Department Visits and Oral Corticosteroid Use

    Science.gov (United States)

    Li, Lingling; Butler, Melissa G.; Fung, Vicki; Kharbanda, Elyse O.; Larkin, Emma K.; Vollmer, William M.; Miroshnik, Irina; Rusinak, Donna; Weiss, Scott T.; Lieu, Tracy; Wu, Ann Chen

    2013-01-01

    Rationale: Statins, or HMG-CoA reductase inhibitors, may aid in the treatment of asthma through their pleiotropic antiinflammatory effects. Objectives: To examine the effect of statin therapy on asthma-related exacerbations using a large population-based cohort. Methods: Statin users aged 31 years or greater with asthma were identified from the Population-Based Effectiveness in Asthma and Lung population, which includes data from five health plans. Statin exposure and asthma exacerbations were assessed over a 24-month observation period. Statin users with a statin medication possession ratio greater than or equal to 80% were matched to non–statin users by age, baseline asthma therapy, site of enrollment, season at baseline, and propensity score, which was calculated based on patient demographics and Deyo-Charlson conditions. Asthma exacerbations were defined as two or more oral corticosteroid dispensings, asthma-related emergency department visits, or asthma-related hospitalizations. The association between statin exposure and each of the three outcome measures was assessed using conditional logistic regression. Measurements and Main Results: Of the 14,566 statin users, 8,349 statin users were matched to a nonuser. After adjusting for Deyo-Charlson conditions that remained unbalanced after matching, among statin users, statin exposure was associated with decreased odds of having asthma-related emergency department visits (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.53–0.77; P statin users with asthma, statin exposure was associated with decreased odds of asthma-related emergency department visits and oral corticosteroid dispensings. PMID:24093599

  15. Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study.

    Science.gov (United States)

    Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

    2017-08-15

    Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Retrospective cohort study. Primary care practices affiliated with 2 academic medical centers. Patients with a presumed adverse reaction to a statin between 2000 and 2011. Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College Hospital.

  16. Do the frequencies of adverse events increase, decrease, or stay the same with long-term use of statins?

    Science.gov (United States)

    Huddy, Karlyn; Dhesi, Pavittarpaul; Thompson, Paul D

    2013-02-01

    Statins are widely used for their cholesterol-lowering properties and proven reduction of cardiovascular disease risk. Many patients take statins as long-term treatment for a variety of conditions without a clear-cut understanding of how treatment duration affects the frequency of adverse effects. We aimed to evaluate whether the frequencies of documented adverse events increase, decrease, or remain unchanged with long-term statin use. We reviewed the established literature to define the currently known adverse effects of statin therapy, including myopathy, central nervous system effects, and the appearance of diabetes, and the frequency of these events with long-term medication use. The frequency of adverse effects associated with long-term statin therapy appears to be low. Many patients who develop side effects from statin therapy do so relatively soon after initiation of therapy, so the frequency of side effects from statin therapy when expressed as a percentage of current users decreases over time. Nevertheless, patients may develop side effects such as muscle pain and weakness years after starting statin therapy; however, the absolute number of patients affected by statin myopathy increases with treatment duration. Also, clinical trials of statin therapy rarely exceed 5 years, so it is impossible to determine with certainty the frequency of long-term side effects with these drugs.

  17. Efficacious and safe tissue-selective controlled gene therapy approaches for the cornea.

    Directory of Open Access Journals (Sweden)

    Rajiv R Mohan

    2011-04-01

    Full Text Available Untargeted and uncontrolled gene delivery is a major cause of gene therapy failure. This study aimed to define efficient and safe tissue-selective targeted gene therapy approaches for delivering genes into keratocytes of the cornea in vivo using a normal or diseased rabbit model. New Zealand White rabbits, adeno-associated virus serotype 5 (AAV5, and a minimally invasive hair-dryer based vector-delivery technique were used. Fifty microliters of AAV5 titer (6.5×10(12 vg/ml expressing green fluorescent protein gene (GFP was topically applied onto normal or diseased (fibrotic or neovascularized rabbit corneas for 2-minutes with a custom vector-delivery technique. Corneal fibrosis and neovascularization in rabbit eyes were induced with photorefractive keratectomy using excimer laser and VEGF (630 ng using micropocket assay, respectively. Slit-lamp biomicroscopy and immunocytochemistry were used to confirm fibrosis and neovascularization in rabbit corneas. The levels, location and duration of delivered-GFP gene expression in the rabbit stroma were measured with immunocytochemistry and/or western blotting. Slot-blot measured delivered-GFP gene copy number. Confocal microscopy performed in whole-mounts of cornea and thick corneal sections determined geometric and spatial localization of delivered-GFP in three-dimensional arrangement. AAV5 toxicity and safety were evaluated with clinical eye exam, stereomicroscopy, slit-lamp biomicroscopy, and H&E staining. A single 2-minute AAV5 topical application via custom delivery-technique efficiently and selectively transduced keratocytes in the anterior stroma of normal and diseased rabbit corneas as evident from immunocytochemistry and confocal microscopy. Transgene expression was first detected at day 3, peaked at day 7, and was maintained up to 16 weeks (longest tested time point. Clinical and slit-lamp eye examination in live rabbits and H&E staining did not reveal any significant changes between AAV5

  18. Association between statin-associated myopathy and skeletal muscle damage.

    Science.gov (United States)

    Mohaupt, Markus G; Karas, Richard H; Babiychuk, Eduard B; Sanchez-Freire, Verónica; Monastyrskaya, Katia; Iyer, Lakshmanan; Hoppeler, Hans; Breil, Fabio; Draeger, Annette

    2009-07-07

    Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10x the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.

  19. Predictors of statin adherence, switching, and discontinuation in the USAGE survey: understanding the use of statins in America and gaps in patient education.

    Science.gov (United States)

    Wei, Melissa Y; Ito, Matthew K; Cohen, Jerome D; Brinton, Eliot A; Jacobson, Terry A

    2013-01-01

    Although statins have been shown to reduce cardiovascular disease mortality, less than half of U.S. adults achieve their low-density lipoprotein cholesterol goal. In many patients initiated on a statin, adherence rates decrease over time. To characterize current and former statin users, identify reasons for the discontinuation or switching of statins, and identify factors associated with adherence. The USAGE survey is a cross-sectional, self-administered Internet-based survey of 10,138 U.S. adults fielded September to October 2011. The following statin users were identified and compared: adherent nonswitchers, adherent switchers, non-adherent switchers, and discontinuers. Univariate and multivariate models using a priori covariates for adherence and discontinuation were examined. Most participants were current statin users who adhered with their prescribed statin (82.5%, n = 8371). Former statin users or discontinuers (12%, n = 1220) cited muscle pain, a side effect, as the primary reason for discontinuation (60%), followed by cost (16%), and then perceived lack of efficacy (13%). Discontinuers were less satisfied with their physicians' explanation of cholesterol treatment, more likely to use the Internet to research statins, and less likely to undergo frequent cholesterol monitoring. Among adherent statin users, the primary reasons for switching were muscle side effects (33%) and cost (32%). Individuals at risk for non-adherence included those with low household income, those who experienced muscle pain as a side effect while on statin therapy, and those taking medication for cardiovascular disease. Statin-related muscle side effects are common and contribute significantly to rates of discontinuation, switching, and non-adherence. Improved physician patient communication about side effects and benefits of statins are necessary to improve both adherence and outcomes. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  20. How to take statins

    Science.gov (United States)

    ... allergies. You are taking other medicines. You have diabetes. You have liver disease. You should not take statins if you ... with your provider about the possible risks for: Liver damage Severe ... High blood sugar, or type 2 diabetes Memory loss Confusion

  1. Statins and polyneuropathy revisited

    DEFF Research Database (Denmark)

    Svendsen, Toke de Koning; Hansen, Peter Nørregaard; García-Rodríguez, Luis Alberto

    2017-01-01

    "); current use was further classified into long-term use (5+ years) and high or low intensity use. We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to examine associations between polyneuropathy and statin use. RESULTS: We included 370 validated cases...

  2. Statins: Evidence for effectiveness

    African Journals Online (AJOL)

    multiple sclerosis,9 and offer added benefit to men with erectile dysfunction.10 Amid this hype and against a backdrop of more the a billion people potentially taking statins,11 the obvious question is whether or not current ..... communications: a narrative review and clinical considerations for older adults. American Journal of ...

  3. Statin Resistance and Export

    DEFF Research Database (Denmark)

    Ley, Ana

    Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), the key enzyme in the mevalonate pathway that leads to the synthesis of cholesterol and ergosterol in animal and fungal cells, respectively. Their extensiveuse in treatment and prevention of cardiovascular diseases...

  4. Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle.

    Science.gov (United States)

    Simakova, Maria N; Bisen, Shivantika; Dopico, Alex M; Bukiya, Anna N

    2017-12-01

    Statins constitute the most commonly prescribed drugs to decrease cholesterol (CLR). CLR is an important modulator of alcohol-induced cerebral artery constriction (AICAC). Using rats on a high CLR diet (2% CLR) we set to determine whether atorvastatin administration (10mg/kg daily for 18-23weeks) modified AICAC. Middle cerebral arteries were pressurized in vitro at 60mmHg and AICAC was evoked by 50mM ethanol, that is within the range of blood alcohol detected in humans following moderate-to-heavy drinking. AICAC was evident in high CLR+atorvastatin group but not in high CLR diet+placebo. Statin exacerbation of AICAC persisted in de-endothelialized arteries, and was blunted by CLR enrichment in vitro. Fluorescence imaging of filipin-stained arteries showed that atorvastatin decreased vascular smooth muscle (VSM) CLR when compared to placebo, this difference being reduced by CLR enrichment in vitro. Voltage- and calcium-gated potassium channels of large conductance (BK) are known VSM targets of ethanol, with their beta1 subunit being necessary for ethanol-induced channel inhibition and resulting AICAC. Ethanol-induced BK inhibition in excised membrane patches from freshly isolated myocytes was exacerbated in the high CLR diet+atorvastatin group when compared to high CLR diet+placebo. Unexpectedly, atorvastatin decreased the amount and function of BK beta1 subunit as documented by immunofluorescence imaging and functional patch-clamp studies. Atorvastatin exacerbation of ethanol-induced BK inhibition disappeared upon artery CLR enrichment in vitro. Our study demonstrates for the first time statin's ability to exacerbate the vascular effect of a widely consumed drug of abuse, this exacerbation being driven by statin modulation of ethanol-induced BK channel inhibition in the VSM via CLR-mediated mechanism. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    DEFF Research Database (Denmark)

    Postmus, Iris; Warren, Helen R; Trompet, Stella

    2016-01-01

    BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed...... a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p

  6. Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study

    NARCIS (Netherlands)

    Kaasenbrood, Lotte; Poulter, Neil R.; Sever, Peter S.; Colhoun, Helen M.; Livingstone, Shona J.; Boekholdt, S. Matthijs; Pressel, Sara L.; Davis, Barry R.; van der Graaf, Yolanda; Visseren, Frank L. J.

    2016-01-01

    In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. Data of 2725 patients

  7. Lipid-lowering therapy: who can benefit

    Directory of Open Access Journals (Sweden)

    Lewis S

    2011-08-01

    Full Text Available Sandra J LewisNorthwest Cardiovascular Institute, Portland, OR, USAAbstract: Cardiovascular disease (CVD is the leading cause of death in the US. Despite the decline in CVD-associated mortality rates in recent years, coronary heart disease (CHD still causes one in every six deaths in this country. Because most CHD risk factors are modifiable (eg, smoking, hypertension, obesity, onset of type 2 diabetes, and dyslipidemia, cardiovascular risk can be reduced by timely and appropriate interventions, such as smoking cessation, diet and lifestyle changes, and lipid-modifying therapy. Dyslipidemia, manifested by elevated low-density lipoprotein cholesterol (LDL-C, is central to the development and progression of atherosclerosis, which can be silent for decades before triggering a first major cardiovascular event. Consequently, dyslipidemia has become a primary target of intervention in strategies for the prevention of cardiovascular events. The guidelines of the Adult Treatment Panel (ATP III, updated in 2004, recommend therapeutic lifestyle changes and the use of lipid-lowering medications, such as statins, to achieve specific LDL-C goals based on a person’s global cardiovascular risk. For high-risk individuals, such as patients with CHD and diabetic patients without CHD, an LDL-C target of < 100 mg/dL is recommended, and statin therapy should be considered to help patients achieve this goal. If correctly dosed in appropriate patients, currently approved statins are generally safe and provide significant cardiovascular benefits in diverse populations, including women, the elderly, and patients with diabetes. A recent primary prevention trial also showed that statins benefit individuals traditionally not considered at high risk of CHD, such as those with no hyperlipidemia but elevated C-reactive protein. Additional evidence suggests that statins may halt or slow atherosclerotic disease progression. Recent evidence confirms the pivotal role of

  8. Are pleiotropic effects of statins real?

    Directory of Open Access Journals (Sweden)

    Alberto Corsini

    2007-11-01

    Full Text Available Alberto Corsini, Nicola Ferri, Michele CortellaroDepartment of Pharmacological Sciences and Department of Clinical Sciences, “Luigi Sacco”, University of Milan, Milan, ItalyAbstract: The clinical benefits of statins are strongly related to their low density lipoproteincholesterol (LDL-C lowering properties. However, because mevalonic acid (MVA, the product of 3-hydroxy-3-methyl-3-glutaryl coenzyme A (HMG-CoA reductase reaction, is the precursor not only of cholesterol but also of nonsteroidal isoprenoid compounds, the inhibition of HMG-CoA reductase may result in pleiotropic effects, independent of their hypocholesterolemic properties. The discrimination between the pleiotropic from LDL-C lowering effects may potentially be more evident during the early phase of treatment since plasma MVA levels drop up to 70% within 1–2 hours while a reduction of LDL-C, detectable after 24 hours, became significant after 6–7 days. Therefore, the deprivation of circulating MVA-derived isoprenoids in the early phase of treatment could be the main mechanism responsible for the atheroprotective effect of statins. This early window of protection in the absence of LDL-C lowering suggests that the anti-inflammatory and the pleiotropic properties of statins may have clinical importance. Therefore, acute coronary syndromes could represent a clinical condition for addressing the early benefits of statins therapy, ie, within 24 h of the event, independent of LDL-C lowering.Keywords: anti-inflammatory effects of statins, mevalonate pathway, LDL lowering, acute coronary syndrome, prenylated proteins

  9. High Flow Nasal Cannula Oxygen Therapy can be used safely in the general paediatric ward using Paediatric Early Warning Scores

    NARCIS (Netherlands)

    Morsing, IE; Tinnevelt, Marcel; Jansen, Nicolaas J.G.; Koomen, E

    2015-01-01

    High Flow Nasal Cannula oxygen therapy (HFNC) is nowadays widely used at paediatric intensive care units (PICU) to provide a safe and comfortable (warm and humidified) oxygen delivery in children with respiratory distress. At general paediatric wards HFNC is hardly used because intensive observation

  10. Statin treatment in multiple sclerosis

    DEFF Research Database (Denmark)

    Pihl-Jensen, Gorm; Tsakiri, Anna; Frederiksen, Jette Lautrup

    2015-01-01

    BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease that leads to progressive disability. Statins [hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors] are widely prescribed drugs in hypercholesterolemia. They exert immunomodulatory and neurotrophic effects and are attractive...... candidates for MS treatment due to reliable safety profiles and favorable costs. Studies of statins in a murine MS model and in open-label trials in MS have shown decreased disease severity. OBJECTIVE: Our objective was to assess current evidence to support statin treatment in MS and clinically isolated......)-β treatment in RRMS, one of statin monotherapy in CIS, one of statin monotherapy in optic neuritis (ON)/CIS, and one of statin monotherapy in secondary progressive MS (SPMS)]. Three trials with eligible characteristics had not been published in peer-reviewed journals and were therefore not included. Due...

  11. Long-Term Statin Administration Does Not Affect Warfarin Time in Therapeutic Range in Australia or Singapore

    Directory of Open Access Journals (Sweden)

    Nijole Bernaitis

    2018-05-01

    Full Text Available Background: Warfarin requires ongoing monitoring of the International Normalised Ratio (INR. This is because numerous factors influence the response, including drug interactions with commonly-prescribed medications, such as statins. The administration of statins with warfarin may change INR; however, there is limited information regarding the effects on warfarin control as measured by time in therapeutic range (TTR. Statins may also alter bleeds with warfarin, but there are conflicting reports demonstrating both increased and decreased bleeds, and limited data on diverse ethnic populations. Therefore, the aim of this study was to determine the effect of statin administration on warfarin control and bleeds in patients in Australia and Singapore. Methods: Retrospective data were collected for patients on warfarin between January and June 2014 in Australia and Singapore. Patient data were used to calculate TTR and bleed events. Concurrent statin therapy was assessed and comparisons of TTR and bleed incidence were made across patient subgroups. Results: Warfarin control in Australia and Singapore was not significantly affected by statins, as measured by TTR (83% and 58%, respectively, frequency of testing, and warfarin doses. In Australia, statin use did not significantly affect bleeds, whilst in Singapore the bleed incidence was significantly lower for patients on statins. Conclusions: Chronic concurrent administration of statins with warfarin does not adversely affect warfarin TTR in Australia or Singapore. In Singapore, patients on statins, compared to no statins, had a lower bleed incidence and this requires further investigation, especially given the potential genetic influences of ethnicity on both statin and warfarin metabolism.

  12. Effect on Fasting Serum Glucose Levels of Adding Ezetimibe to Statins in Patients With Nondiabetic Hypercholesterolemia.

    Science.gov (United States)

    Toth, Peter P; Catapano, Alberico L; Farnier, Michel; Foody, Joanne; Tomassini, Joanne E; Jensen, Erin; Polis, Adam B; Hanson, Mary E; Musliner, Thomas A; Tershakovec, Andrew M

    2016-12-15

    Statin therapy is associated with a slightly increased risk of developing diabetes mellitus and insulin resistance in patients without diabetes. Ezetimibe combined with statins may be considered for high-risk patients who do not achieve optimal low-density lipoprotein cholesterol lowering on statin monotherapy or who are statin intolerant. Changes in fasting serum glucose (FSG) levels during ezetimibe, ezetimibe/statin, and statin treatments were assessed using data pooled from clinical trials in hypercholesterolemic and heterozygous familial hypercholesterolemic patients, who were or were not receiving statin therapy. Study types included first-line trials in statin-naive/wash-out patients and second-line add-on and uptitration studies in patients on stable statin therapy. Similar analyses of FSG changes were performed separately for each study type in patients who were nondiabetic at baseline. Across all study types and treatments, mean FSG increases from baseline were small (0.5 to 3.7 mg/dl with ezetimibe/statin; 0.2 to 4.6 mg/dl with statins) and decreased over time; between-treatment differences (0.3 to 1.4 mg/dl) were nonsignificant for all comparisons. Proportions of patients with elevated FSG ≥126 mg/dl during therapy were low and similar for all treatments in the overall cohort (1.2% to 4.3%). Elevations were highest (3.3% to 25.7%) among patients with baseline factors characteristic of metabolic syndrome and prediabetes, including higher FSG, body mass index, and triglyceride levels, and numerically lower baseline high-density lipoprotein cholesterol; however, these factors were not related to FSG increases. Changes in low-density lipoprotein cholesterol, body mass index, high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B were not significantly correlated with FSG increases. In conclusion, statin therapy was associated with small FSG increases, and the addition of ezetimibe did not further increase FSG levels beyond those of

  13. Investigating the prevalence, predictors, and prognosis of suboptimal statin use early after a non-ST elevation acute coronary syndrome.

    Science.gov (United States)

    Turner, Richard M; Yin, Peng; Hanson, Anita; FitzGerald, Richard; Morris, Andrew P; Stables, Rod H; Jorgensen, Andrea L; Pirmohamed, Munir

    High-potency statin therapy is recommended in the secondary prevention of cardiovascular disease but discontinuation, dose reduction, statin switching, and/or nonadherence occur in practice. To determine the prevalence and predictors of deviation from high-potency statin use early after a non-ST elevation acute coronary syndrome (NSTE-ACS) and its association with subsequent major adverse cardiovascular events (MACE) and all-cause mortality (ACM). A total of 1005 patients from a UK-based prospective NSTE-ACS cohort study discharged on high-potency statin therapy (atorvastatin 80 mg, rosuvastatin 20 mg, or 40 mg daily) were included. At 1 month, patients were divided into constant high-potency statin users, and suboptimal users incorporating statin discontinuation, dose reduction, switching statin to a lower equivalent potency, and/or statin nonadherence. Follow-up was a median of 16 months. There were 156 suboptimal (∼15.5%) and 849 constant statin users. Factors associated in multivariable analysis with suboptimal statin occurrence included female sex (odds ratio 1.75, 95% confidence interval [CI] 1.14-2.68) and muscular symptoms (odds ratio 4.28, 95% CI 1.30-14.08). Suboptimal statin use was associated with increased adjusted risks of time to MACE (hazard ratio 2.10, 95% CI 1.25-3.53, P = .005) and ACM (hazard ratio 2.46, 95% CI 1.38-4.39, P = .003). Subgroup analysis confirmed that the increased MACE/ACM risks were principally attributable to statin discontinuation or nonadherence. Conversion to suboptimal statin use is common early after NSTE-ACS and is partly related to muscular symptoms. Statin discontinuation or non-adherence carries an adverse prognosis. Interventions that preserve and enhance statin utilization could improve post NSTE-ACS outcomes. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  14. Statin-induced focal myositis of the upper extremity. A report of two cases

    Energy Technology Data Exchange (ETDEWEB)

    Wagner, M., E-mail: wagner.radiologie@herzchirurgie.de [Department of Radiology, Herz- und Gefaessklinik GmbH, Salzburger Leite 1, D-97616 Bad Neustadt an der Saale (Germany); Muehldorfer-Fodor, M.; Prommersberger, K.J. [Department of Handsurgery, Herz- und Gefaessklinik GmbH, Bad Neustadt an der Saale (Germany); Schmitt, R. [Department of Radiology, Herz- und Gefaessklinik GmbH, Salzburger Leite 1, D-97616 Bad Neustadt an der Saale (Germany)

    2011-02-15

    Statins are widely used to lower increased cholesterol levels with the aim to prevent major cardiovascular events. However, they bare the risk of myotoxic side effects. We report on two patients with focal weakness and pain in the upper extremities. In both patients, abnormal MRI signal heights in the muscle groups involved were indicative of the final diagnosis of focal myositis during statin therapy.

  15. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    NARCIS (Netherlands)

    Postmus, Iris; Warren, Helen R.; Trompet, Stella; Arsenault, Benoit J.; Avery, Christy L.; Bis, Joshua C.; Chasman, Daniel I.; de Keyser, Catherine E.; Deshmukh, Harshal A.; Evans, Daniel S.; Feng, QiPing; Li, Xiaohui; Smit, Roelof A. J.; Smith, Albert V.; Sun, Fangui; Taylor, Kent D.; Arnold, Alice M.; Barnes, Michael R.; Barratt, Bryan J.; Betteridge, John; Boekholdt, S. Matthijs; Boerwinkle, Eric; Buckley, Brendan M.; Chen, Y.-D. Ida; de Craen, Anton J. M.; Cummings, Steven R.; Denny, Joshua C.; Dubé, Marie Pierre; Durrington, Paul N.; Eiriksdottir, Gudny; Ford, Ian; Guo, Xiuqing; Harris, Tamara B.; Heckbert, Susan R.; Hofman, Albert; Hovingh, G. Kees; Kastelein, John J. P.; Launer, Leonore J.; Liu, Ching-Ti; Liu, Yongmei; Lumley, Thomas; McKeigue, Paul M.; Munroe, Patricia B.; Neil, Andrew; Nickerson, Deborah A.; Nyberg, Fredrik; O'Brien, Eoin; O'Donnell, Christopher J.; Post, Wendy; Poulter, Neil; Vasan, Ramachandran S.; Rice, Kenneth; Rich, Stephen S.; Rivadeneira, Fernando; Sattar, Naveed; Sever, Peter; Shaw-Hawkins, Sue; Shields, Denis C.; Slagboom, P. Eline; Smith, Nicholas L.; Smith, Joshua D.; Sotoodehnia, Nona; Stanton, Alice; Stott, David J.; Stricker, Bruno H.; Stürmer, Til; Uitterlinden, André G.; Wei, Wei-Qi; Westendorp, Rudi G. J.; Whitsel, Eric A.; Wiggins, Kerri L.; Wilke, Russell A.; Ballantyne, Christie M.; Colhoun, Helen M.; Cupples, L. Adrienne; Franco, Oscar H.; Gudnason, Vilmundur; Hitman, Graham; Palmer, Colin N. A.; Psaty, Bruce M.; Ridker, Paul M.; Stafford, Jeanette M.; Stein, Charles M.; Tardif, Jean-Claude; Caulfield, Mark J.; Jukema, J. Wouter; Rotter, Jerome I.; Krauss, Ronald M.

    2016-01-01

    In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. We performed a meta-analysis of genome-wide

  16. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    NARCIS (Netherlands)

    D. Postmus (Douwe); H. Warren (Helen); S. Trompet (Stella); B.J. Arsenault (Benoit J.); C.L. Avery; J.C. Bis (Joshua); D.I. Chasman (Daniel); C.E. de Keyser (Catherina Elisabeth); H. Deshmukh (Harshal); D.S. Evans (Daniel); Feng, Q. (QiPing); X. Li (Xiaohui); Smit, R.A.J. (Roelof A.J.); A.V. Smith (Albert Vernon); F. Sun (Fangui); K.D. Taylor (Kent); A.M. Arnold (Alice M.); M.J. Barnes (Michael); B.J. Barratt (Bryan J.); J. Betteridge (John); S.M. Boekholdt (Matthijs); E.A. Boerwinkle (Eric); B.M. Buckley (Brendan M.); Y.D. Chen (Y.); A.J. de Craen (Anton); S. Cummings; Denny, J.C. (Joshua C.); G.P. Dubé (Gregory); P.N. Durrington (Paul); G. Eiriksdottir (Gudny); I. Ford (Ian); X. Guo (Xiuqing); T.B. Harris (Tamara); S.R. Heckbert (Susan); A. Hofman (Albert); G. Kees Hovingh; J.J.P. Kastelein (John); Launer, L.J. (Leonore J.); Liu, C.-T. (Ching-Ti); Y. Liu (YongMei); T. Lumley (Thomas); P.M. Mckeigue (Paul); P. Munroe (Patricia); A. Neil (Andrew); D.A. Nickerson (Deborah); F. Nyberg (Fredrik); E. O'Brien (Eoin); C.J. O'Donnell (Christopher); W.S. Post (Wendy S.); N.R. Poulter (Neil); R.S. Vasan (Ramachandran Srini); K.M. Rice (Kenneth); S.S. Rich (Stephen); F. Rivadeneira Ramirez (Fernando); N. Sattar (Naveed); P. Sever (Peter); S. Shaw-Hawkins (Sue); D.C. Shields (Denis C.); P.E. Slagboom (Eline); N.L. Smith (Nicholas); J.D. Smith (Joshua D.); N. Sotoodehnia (Nona); A. Stanton (Alice); D.J. Stott (David. J.); B.H.Ch. Stricker (Bruno); T. Stürmer; A.G. Uitterlinden (André); W.-Q. Wei (Wei-Qi); R.G.J. Westendorp (Rudi); E.A. Whitsel (Eric A.); K.L. Wiggins (Kerri); R.A. Wilke (Russell A.); C. Ballantyne (Christie); H.M. Colhoun (H.); L.A. Cupples (Adrienne); O.H. Franco (Oscar); V. Gudnason (Vilmundur); G.A. Hitman (Graham); C.N.A. Palmer (Colin); B.M. Psaty (Bruce); P.M. Ridker (Paul); J.M. Stafford (Jeanette M.); Stein, C.M. (Charles M.); J.-C. Tardif (Jean-Claude); M. Caulfield (Mark); J.W. Jukema (Jan Wouter); Rotter, J.I. (Jerome I.); R.M. Krauss (Ronald)

    2016-01-01

    textabstractBackground In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We

  17. Statin-induced focal myositis of the upper extremity. A report of two cases

    International Nuclear Information System (INIS)

    Wagner, M.; Muehldorfer-Fodor, M.; Prommersberger, K.J.; Schmitt, R.

    2011-01-01

    Statins are widely used to lower increased cholesterol levels with the aim to prevent major cardiovascular events. However, they bare the risk of myotoxic side effects. We report on two patients with focal weakness and pain in the upper extremities. In both patients, abnormal MRI signal heights in the muscle groups involved were indicative of the final diagnosis of focal myositis during statin therapy.

  18. Statin use is associated with reduced all-cause mortality after endovascular abdominal aortic aneurysm repair.

    NARCIS (Netherlands)

    Leurs, L.J.; Visser, P.; Laheij, R.J.F.; Buth, J.; Harris, P.L.; Blankensteijn, J.D.

    2006-01-01

    It has been shown that preoperative statin therapy reduces all-cause and cardiovascular mortality in patients undergoing major noncardiac vascular surgery. In this report, we investigated the influence of statin use on early and late outcome following endovascular abdominal aortic aneurysm repair

  19. Statin intolerance - an attempt at a unified definition. Position paper from an International Lipid Expert Panel

    NARCIS (Netherlands)

    Banach, Maciej; Rizzo, Manfredi; Toth, Peter P.; Farnier, Michel; Davidson, Michael H.; Al-Rasadi, Khalid; Aronow, Wilbert S.; Athyros, Vasilis; Djuric, Dragan M.; Ezhov, Marat V.; Greenfield, Robert S.; Hovingh, G. Kees; Kostner, Karam; Serban, Corina; Lighezan, Daniel; Fras, Zlatko; Moriarty, Patrick M.; Muntner, Paul; Goudev, Assen; Ceska, Richard; Nicholls, Stephen J.; Broncel, Marlena; Nikolic, Dragana; Pella, Daniel; Puri, Raman; Rysz, Jacek; Wong, Nathan D.; Bajnok, Laszlo; Jones, Steven R.; Ray, Kausik K.; Mikhailidis, Dimitri P.

    2015-01-01

    Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has

  20. Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study

    NARCIS (Netherlands)

    Citgez, Emanuel; van der Palen, Job; Koehorst-Ter Huurne, Kirsten; Movig, Kris; van der Valk, Paul; Brusse-Keizer, Marjolein

    2016-01-01

    BACKGROUND: Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under

  1. Non-every day statin administration--a literature review.

    Science.gov (United States)

    Elis, Avishay; Lishner, Michael

    2012-07-01

    Statins are the treatment of choice for lowering LDL-C levels and reducing cardiovascular events. They have a remarkable safety profile, although some patients do not tolerate them. The aim of the study was to summarize the existing data on non-every day statin administration regimens. We searched the MEDLINE databases to identify articles on non-every day statin administration, published between 1990 and January 2010. All publications regardless of methodology, design, size, or language were included. Data extracted included study design, duration and aims, type of statin, therapeutic regimen, patient characteristics, effectiveness, tolerability, and costs. The 21 retrieved articles were characterized by small sample size, short follow up period, and a preponderance of males and "primary" prevention cases. Several lacked randomization or a control group. The heterogeneity of the study groups, medications, doses, design and aims precluded a pooled or meta-analysis. The most reported and effective regimens were atorvastatin and rosuvastatin on alternate days. These regimens, with or without other lipid lowering agents, were well tolerated even among subjects with previous statin intolerance, and produced meaningful cost savings. Nevertheless, the effectiveness of these regimens on cardiovascular events was not clarified. Atorvastatin or rosuvastatin on alternate days might be considered for patients who are intolerant to statin therapy. Further studies are needed to evaluate the effect of these regimens on cardiovascular events. Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  2. Effects of Plasma Lipids and Statins on Cognitive Function.

    Science.gov (United States)

    Li, Rui; Wang, Tian-Jun; Lyu, Pei-Yuan; Liu, Yang; Chen, Wei-Hong; Fan, Ming-Yue; Xu, Jing

    2018-02-20

    Dementia is the fourth most common cause of death in developed countries. The relationship between plasma lipids and cognitive function is complex and controversial. Due to the increasing life expectancy of the population, there is an urgent need to control vascular risk factors and to identify therapies to prevent and treat both cognitive impairment and dementia. Here, we reviewed the effects of plasma lipids and statins on cognitive function. We searched the PubMed database for research articles published through November 2017 with key words including "plasma lipids," "hyperlipidemia," "hypercholesterolemia," "statins," and "cognition function." Articles were retrieved and reviewed to analyze the effects of plasma lipids and statins on cognitive function and the mechanisms underlying these effects. Many studies have examined the relationship between plasma lipids and cognitive function, but no definitive conclusions can be drawn. The mechanisms involved may include blood-brain barrier injury, the influence on small blood vessels in the brain, the influence on amyloid deposition, and a neuroprotective effect. To date, most studies of statins and cognition have been observational, with few randomized controlled trials. Therefore, firm conclusions regarding whether mid- or long-term statin use affects cognition function and dementia remain elusive. However, increasing concern exists that statins may be a causative factor for cognitive problems. These adverse effects appear to be rare and likely represent a yet-to-be-defined vulnerability in susceptible individuals. The association between plasma lipids and cognition, the mechanism of the influence of plasma lipids on cognitive function, and the association between statins and cognitive function are complex issues and currently not fully understood. Future research aimed at identifying the mechanisms that underlie the effects of plasma lipids and statins on cognition will not only provide important insight into the

  3. Statin use and kidney cancer outcomes: A propensity score analysis.

    Science.gov (United States)

    Nayan, Madhur; Finelli, Antonio; Jewett, Michael A S; Juurlink, David N; Austin, Peter C; Kulkarni, Girish S; Hamilton, Robert J

    2016-11-01

    Studies evaluating the association between statin use and survival outcomes in renal cell carcinoma have demonstrated conflicting results. Our objective was to evaluate this association in a large clinical cohort by using propensity score methods to reduce confounding from measured covariates. We performed a retrospective review of 893 patients undergoing nephrectomy for unilateral, M0 renal cell carcinoma between 2000 and 2014 at a tertiary academic center. Inverse probability of treatment weights were derived from a propensity score model based on clinical, surgical, and pathological characteristics. We used Cox proportional hazard models to evaluate the association between statin use and disease-free survival, cancer-specific survival, and overall survival in the sample weighted by the inverse probability of treatment weights. A secondary analysis was performed matching statin users 1:1 to statin nonusers on the propensity score. Of the 893 patients, 259 (29%) were on statins at the time of surgery. Median follow-up was 47 months (interquartile range: 20-80). Statin use was not significantly associated with disease-free survival (hazard ratio [HR] = 1.09, 95% CI: 0.65-1.81), cancer-specific survival (HR = 0.90, 95% CI: 0.40-2.01), or overall survival (HR = 0.89, 95% CI: 0.55-1.44). Similar results were observed when using propensity score matching. The present study found no significant association between statin use and kidney cancer outcomes. Population-based studies are needed to further evaluate the role of statins in kidney cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Statin-activated nuclear receptor PXR promotes SGK2 dephosphorylation by scaffolding PP2C to induce hepatic gluconeogenesis.

    Science.gov (United States)

    Gotoh, Saki; Negishi, Masahiko

    2015-09-22

    Statin therapy is known to increase blood glucose levels in humans. Statins utilize pregnane X receptor (PXR) and serum/glucocorticoid regulated kinase 2 (SGK2) to activate phosphoenolpyruvate carboxykinase 1 (PEPCK1) and glucose-6-phosphatase (G6Pase) genes, thereby increasing glucose production in human liver cells. Here, the novel statin/PXR/SGK2-mediated signaling pathway has now been characterized for hepatic gluconeogenesis. Statin-activated PXR scaffolds the protein phosphatase 2C (PP2C) and SGK2 to stimulate PP2C to dephosphorylate SGK2 at threonine 193. Non-phosphorylated SGK2 co-activates PXR-mediated trans-activation of promoters of gluconeogenic genes in human liver cells, thereby enhancing gluconeogenesis. This gluconeogenic statin-PXR-SGK2 signal is not present in mice, in which statin treatment suppresses hepatic gluconeogenesis. These findings provide the basis for statin-associated side effects such as an increased risk for Type 2 diabetes.

  5. Statin intolerance – an attempt at a unified definition. Position paper from an International Lipid Expert Panel

    Science.gov (United States)

    Rizzo, Manfredi; Toth, Peter P.; Farnier, Michel; Davidson, Michael H.; Al-Rasadi, Khalid; Aronow, Wilbert S.; Athyros, Vasilis; Djuric, Dragan M.; Ezhov, Marat V.; Greenfield, Robert S.; Hovingh, G. Kees; Kostner, Karam; Serban, Corina; Lighezan, Daniel; Fras, Zlatko; Moriarty, Patrick M.; Muntner, Paul; Goudev, Assen; Ceska, Richard; Nicholls, Stephen J.; Broncel, Marlena; Nikolic, Dragana; Pella, Daniel; Puri, Raman; Rysz, Jacek; Wong, Nathan D.; Bajnok, Laszlo; Jones, Steven R.; Ray, Kausik K.; Mikhailidis, Dimitri P.

    2015-01-01

    Statins are one of the most commonly prescribed drugs in clinical practice. They are usually well tolerated and effectively prevent cardiovascular events. Most adverse effects associated with statin therapy are muscle-related. The recent statement of the European Atherosclerosis Society (EAS) has focused on statin associated muscle symptoms (SAMS), and avoided the use of the term ‘statin intolerance’. Although muscle syndromes are the most common adverse effects observed after statin therapy, excluding other side effects might underestimate the number of patients with statin intolerance, which might be observed in 10–15% of patients. In clinical practice, statin intolerance limits effective treatment of patients at risk of, or with, cardiovascular disease. Knowledge of the most common adverse effects of statin therapy that might cause statin intolerance and the clear definition of this phenomenon is crucial to effectively treat patients with lipid disorders. Therefore, the aim of this position paper was to suggest a unified definition of statin intolerance, and to complement the recent EAS statement on SAMS, where the pathophysiology, diagnosis and the management were comprehensively presented. PMID:25861286

  6. Genetic determinants of statin intolerance

    Directory of Open Access Journals (Sweden)

    Pollex Rebecca L

    2007-03-01

    Full Text Available Abstract Background Statin-related skeletal muscle disorders range from benign myalgias – such as non-specific muscle aches or joint pains without elevated serum creatinine kinase (CK concentration – to true myositis with >10-fold elevation of serum CK, to rhabdomyolysis and myoglobinuria. The genetic basis of statin-related muscle disorders is largely unknown. Because mutations in the COQ2 gene are associated with severe inherited myopathy, we hypothesized that common, mild genetic variation in COQ2 would be associated with inter-individual variation in statin intolerance. We studied 133 subjects who developed myopathy on statin monotherapy and 158 matched controls who tolerated statins without incident or complaint. Results COQ2 genotypes, based on two single nucleotide polymorphisms (SNP1 and SNP2 and a 2-SNP haplotype, all showed significant associations with statin intolerance. Specifically, the odds ratios (with 95% confidence intervals for increased risk of statin intolerance among homozygotes for the rare alleles were 2.42 (0.99 to 5.89, 2.33 (1.13 to 4.81 and 2.58 (1.26 to 5.28 for SNP1 and SNP2 genotypes, and the 2-SNP haplotype, respectively. Conclusion These preliminary pharmacogenetic results, if confirmed, are consistent with the idea that statin intolerance which is manifested primarily through muscle symptoms is associated with genomic variation in COQ2 and thus perhaps with the CoQ10 pathway.

  7. Statin-associated muscle symptoms-Managing the highly intolerant.

    Science.gov (United States)

    Backes, James M; Ruisinger, Janelle F; Gibson, Cheryl A; Moriarty, Patrick M

    Musculoskeletal symptoms are the most commonly reported adverse effects associated with statin therapy. Yet, certain data indicate that these symptoms often present in populations with underlying musculoskeletal complaints and are not likely statin related. Switching statins or using lower doses resolves muscle complaints in most patients. However, there is a growing population of individuals who experience intolerable musculoskeletal symptoms with multiple statins, regardless of the individual agent or prescribed dose. Recent randomized, placebo-controlled trials enrolling highly intolerant subjects provide significant insight regarding statin-associated muscle symptoms (SAMS). Notable findings include the inconsistency with reproducing muscle complaints, as approximately 40% of subjects report SAMS when taking a statin but not while receiving placebo, but a substantial cohort reports intolerable muscle symptoms with placebo but none when on a statin. These data validate SAMS for those likely experiencing true intolerance, but for others, suggest a psychosomatic component or misattribution of the source of pain and highlights the importance of differentiating from the musculoskeletal symptoms caused by concomitant factors. Managing the highly intolerant requires candid patient counseling, shared decision-making, eliminating contributing factors, careful clinical assessment and the use of a myalgia index score, and isolating potential muscle-related adverse events by gradually reintroducing drug therapy with the utilization of intermittent dosing of lipid-altering agents. We provide a review of recent data and therapeutic guidance involving a focused step-by-step approach for managing SAMS among the highly intolerant. Such strategies usually allow for clinically meaningful reductions in low-density lipoprotein cholesterol and an overall lowering of cardiovascular risk. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial

    DEFF Research Database (Denmark)

    Ridker, P.M.; Genest, J.; Boekholdt, S.M.

    2010-01-01

    Background HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment. Methods...... Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more. Participants were randomly allocated...... these quartiles and the JUPITER primary endpoint of first non-fatal myocardial infarction or stroke, hospitalisation for unstable angina, arterial revascularisation, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT00239681. Findings For 17802 patients in the JUPITER trial...

  9. Statin cost effectiveness in primary prevention: A systematic review of the recent cost-effectiveness literature in the United States

    Directory of Open Access Journals (Sweden)

    Mitchell Aaron P

    2012-07-01

    Full Text Available Abstract Background The literature on the cost-effectiveness of statin drugs in primary prevention of coronary heart disease is complex. The objective of this study is to compare the disparate results of recent cost-effectiveness analyses of statins. Findings We conducted a systematic review of the literature on statin cost-effectiveness. The four studies that met inclusion criteria reported varying conclusions about the cost-effectiveness of statin treatment, without a clear consensus as to whether statins are cost-effective for primary prevention. However, after accounting for each study’s assumptions about statin costs, we found substantial agreement among the studies. Studies that assumed statins to be more expensive found them to be less cost-effective, and vice-versa. Furthermore, treatment of low-risk groups became cost-effective as statins became less expensive. Conclusions Drug price is the primary determinant of statin cost-effectiveness within a given risk group. As more statin drugs become generic, patients at low risk for coronary disease may be treated cost-effectively. Though many factors must be weighed in any medical decision, from a cost-effectiveness perspective, statins may now be considered an appropriate therapy for many patients at low risk for heart disease.

  10. Clinical Profile of Statin Intolerance in the Phase 3 GAUSS-2 Study.

    Science.gov (United States)

    Cho, Leslie; Rocco, Michael; Colquhoun, David; Sullivan, David; Rosenson, Robert S; Dent, Ricardo; Xue, Allen; Scott, Rob; Wasserman, Scott M; Stroes, Erik

    2016-06-01

    Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an anti-PCSK9 antibody in Statin Intolerant Subjects Study (GAUSS-2; NCT 01763905). GAUSS-2 compared evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) to ezetimibe in hypercholesterolemic patients who discontinued statin therapy due to statin-associated muscle symptoms (SAMS). GAUSS-2 was a 12-week, double-blind, placebo-controlled, randomized study that enrolled patients with elevated LDL-C who were either not on a statin or able to tolerate only a low-dose due to SAMS. Patients had received ≥2 statins and were unable to tolerate any statin dose or increase in dose above a specified weekly dose due to SAMS. Three hundred seven patients (mean [SD] age, 62 [10] years; 54 % males) were randomized 2:1 (evolocumab:ezetimibe). Mean (SD) LDL-C was 4.99 (1.51) mmol/L. Patients had used ≥2 (100 %), ≥3 (55 %), or ≥4 (21 %) statins. Coronary artery disease was present in 29 % of patients. Statin-intolerant symptoms were myalgia in 80 % of patients, weakness in 39 %, and more serious complications in 20 %. In 98 % of patients, SAMS interfered with normal daily activity; in 52 %, symptoms precluded moderate exertion. Evaluation of the GAUSS-2 trial population of statin-intolerant patients demonstrates that most patients were high risk with severely elevated LDL-C and many had statin-associated muscle symptoms that interfered with their quality of life.

  11. Nonadherence to statins: individualized intervention strategies outside the pill box

    Directory of Open Access Journals (Sweden)

    Lansberg P

    2018-05-01

    Full Text Available Peter Lansberg,1 Andre Lee,2 Zhen-Vin Lee,3 Kannan Subramaniam,4 Sajita Setia5 1Department of Pediatrics, University Medical Center, Groningen, the Netherlands; 2Department of Pharmacy, National University of Singapore, Singapore; 3Cardiology Unit, Department of Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia; 4Global Medical Affairs, Asia-Pacific region, Pfizer Australia, West Ryde, NSW, Australia; 5Medical Affairs, Pfizer Pte Ltd, Singapore Abstract: Poor adherence to statin therapy is linked to significantly increased risk of cardiovascular events and death. Unfortunately, adherence to statins is far from optimal. This is an alarming concern for patients prescribed potentially life-saving cholesterol-lowering medication, especially for those at high risk of cardiovascular events. Research on statin adherence has only recently garnered broader attention; hence, major reasons unique to adherence to statin therapy need to be identified as well as suggestions for countermeasures. An integrated approach to minimizing barriers and enhancing facilitation at the levels of the patient, provider, and health system can help address adherence issues. Health care professionals including physicians, pharmacists, and nurses have an obligation to improve patient adherence, as routine care. In order to achieve sustained results, a multifaceted approach is indispensable. Keywords: cardiovascular disease, nonadherence, nocebo, myopathy, statins

  12. Guideline concordance of new statin prescriptions: who got a statin?

    Science.gov (United States)

    Cascino, Thomas; Vali, Marzieh; Redberg, Rita; Bravata, Dawn M; Boscardin, John; Eilkhani, Elnaz; Keyhani, Salomeh

    2017-09-01

    Statins are recommended to reduce serum cholesterol in patients at risk for atherosclerotic cardiovascular disease. Despite the prevalence of statin use, little is known about the indications for new prescriptions. We assessed the concordance of new statin prescriptions in the Veterans Health Administration (VHA) compared with the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III) guidelines (the guidelines in force in 2012) and the American College of Cardiology (ACC)-American Heart Association (AHA) 2013 guidelines. Cross-sectional study. We identified every patient who received a new prescription (no statin use in the prior year) in the VHA in 2012. Patients were excluded if they had incomplete data, triglycerides greater than 400 mg/dL, or fewer than 2 primary care visits to ensure adequate baseline data to calculate Framingham and ACC-AHA 2013 risk scores. We identified 250,243 new statin prescriptions in 2012 in the VHA, with 121,081 meeting inclusion criteria. Among new prescriptions, 68% were prescribed for primary prevention and 32% were prescribed for secondary prevention. Among patients receiving new statins for primary prevention, 48% did not have an indication supported by the ATP III guideline and 20% did not have an indication supported by the ACC/AHA guideline. Overall, approximately 19% of patients may have received a statin for an indication not supported by either guideline. Veterans are commonly prescribed statins for indications not supported by professional society guidelines. The finding of common use of statins outside established guidelines represents an opportunity to improve the quality and value of the healthcare delivery.

  13. Maximal safe dose of I-131 after failure of standard fixed dose therapy in patients with differentiated thyroid carcinoma

    International Nuclear Information System (INIS)

    Lee, Jong-Jin; Chung, June-Key; Kim, Sung-Eun; Kang, Won-Jun; Park, Do-Joon; Lee, Dong-Soo; Cho, Bo-Youn; Lee, Myung-Chul

    2008-01-01

    The maximal safe dose (MSD) on the basis of bone marrow irradiation levels allows the delivery of a large amount of I-131 to thyroid cancer tissue. The efficacy of MSD therapy in differentiated metastatic thyroid cancers that persisted after conventional fixed dose therapy is investigated. Forty-seven differentiated thyroid carcinoma patients with non-responsive residual disease despite repetitive fixed dose I-131 therapy were enrolled in this study. Their postoperative pathologies were 43 papillary carcinomas and 4 follicular carcinomas. The MSD was calculated with the Memorial Sloan-Kettering Cancer Center protocol using serial blood samples. The MSDs were administered at intervals of 6 months. Treatment responses were evaluated using I-131 whole-body scans and serum thyroglobulin measurements. The mean calculated MSD was 12.5±2.1 GBq (339.6±57.5 mCi). Of the 46 patients, 7 (14.9%) showed complete remission, 15 (31.9%) partial remission, 19 (40.4%) stable disease, and 6 (12.8%) disease progression. Of the patients who showed complete or partial remission, 15 (65%) showed response after the first MSD session and 6 (26%) showed response after the second session. Twenty-nine patients (62%) experienced transient cytopenia after therapy, but three did not recover to the baseline level. The maximal safe dose provides an effective means of treatment in patients who failed to respond adequately to conventional fixed dose therapy. I-131 MSD therapy can be considered in patients who fail fixed dose therapy. (author)

  14. THE PROBLEM OF STATIN USE IN PATIENTS WITH CARDIOVASCULAR DISEASES AND CONCOMITANT LIVER DISEASES. WHAT PREVENTS OVERCOMING STATINOPHOBIA?

    Directory of Open Access Journals (Sweden)

    S. N. Bel'diev

    2016-01-01

    Full Text Available According to a recent study, Russian physicians often and sometimes unreasonably find it impossible to use statins in patients with cardiovascular diseases and concomitant chronic liver diseases. Analysis of domestic publications of recent years reveals the following factors which can impede overcoming statinophobia: 1 fragmentary and contradictory statement of the problem "Statins and liver" in Russian clinical guidelines for management of patients with high cardiovascular risk; 2 common perception that isolated transaminase increase in response to statin therapy is an indicator of "cytolysis" or "cytolytic syndrome"; 3 unreasonably overestimated lipid-lowering activity of combination therapy with low doses of statins and ursodeoxycholic acid; 4 view of the inadmissibility of statin use in patients with transaminase levels more than three upper limit of normal. To overcome these shortcomings and mistakes it seems appropriate to issue national clinical guidelines on statin use in high cardiovascular risk patients with underlying liver disease and/or with elevated transaminases.

  15. Gender difference in hipolipemic and anti-inflammatory effects of statins in diabetics with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Đinđić Boris

    2009-01-01

    Full Text Available Background/Aim. Statins produce hipolipemic and pleotropic effects on markers of inflammation with stabilization of atheromatous plaque. The aim of this paper was to examine gender difference in hipolipemic and antiinflammatory effects of statins in patients with diabetes mellitus (DM type 2 with coronary artery disease (CAD. Methods. Sixty dyslipidemic patients with DM type 2 were analyzed. Lifestyle modification and hipolipemic diet were applied in all patients divided into two groups: 30 patients with statins therapy (20 mg of simvastatin or equivalent dose of some other statins, during 3 months and 30 patients without statins therapy. Estimation of obesity, quality of glicoregulation, and determination of inflammatory parameters: Creactive protein (CRP, fibrinogen, total and differential leukocyte count, intracellular adhesive molecules (ICAM-1, vascular adhesive molecule-(VCAM-1 and lipid profile (total cholesterol - TC, LDL-C, HDL-C, triglicerides - TG were done. Results. Women with DM type 2 were more obese and had significant disturbances in lipid profiles, glicoregulation and inflammatory markers compared to men. Statins therapy significantly improved all lipid parameters and quality of glicoregulation in women, while there were only significant reduction of LDL-C and nonHDL-C in males. There were more significant reductions of inflammatory markers in women as compared to men with statins therapy. In the group without statins there was not such significant reduction. Concentration of ICAM-1 was the lowest in men on statins therapy, while there were no significant variability of VCAM-1 values between groups and genders. Conclusion. Women with DM type 2 and CAD have more prominent lipoprotein disorders and impaired glicoregulation with expression of enhanced proinflamatory state which could not be seen in men. Statins therapy exerts more favorable effects in women leading to stabilization of lipoprotein profiles, improvement of

  16. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update.

    Science.gov (United States)

    Mancini, G B John; Tashakkor, A Yashar; Baker, Steven; Bergeron, Jean; Fitchett, David; Frohlich, Jiri; Genest, Jacques; Gupta, Milan; Hegele, Robert A; Ng, Dominic S; Pearson, Glen J; Pope, Janet

    2013-12-01

    The Proceedings of a Canadian Working Group Consensus Conference, first published in 2011, provided a summary of statin-associated adverse effects and intolerance and management suggestions. In this update, new clinical studies identified since then that provide further insight into effects on muscle, cognition, cataracts, diabetes, kidney disease, and cancer are discussed. Of these, the arenas of greatest controversy pertain to purported effects on cognition and the emergence of diabetes during long-term therapy. Regarding cognition, the available evidence is not strongly supportive of a major adverse effect of statins. In contrast, the linkage between statin therapy and incident diabetes is more firm. However, this risk is more strongly associated with traditional risk factors for new-onset diabetes than with statin itself and any possible negative effect of new-onset diabetes during statin treatment is far outweighed by the cardiovascular risk reduction benefits. Additional studies are also discussed, which support the principle that systematic statin rechallenge, and lower or intermittent statin dosing strategies are the main methods for dealing with suspected statin intolerance at this time. Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  17. Acylation-stimulating protein is a surrogate biomarker for acute myocardial infarction: Role of statins

    Directory of Open Access Journals (Sweden)

    Hayder M Al-Kuraishy

    2017-01-01

    Conclusion: ASP levels are elevated in patients with acute MI and regarded as surrogate biomarker for acute MI also; therapy with statins leads to significant reduction in ASP levels compared to nonstatins-treated patients that presented with acute MI.

  18. Effect of Statin Use on Outcomes of Adults with Candidemia

    Science.gov (United States)

    Cuervo, Guillermo; Garcia-Vidal, Carolina; Nucci, Marcio; Puchades, Francesc; Fernández-Ruiz, Mario; Mykietiuk, Analía; Manzur, Adriana; Gudiol, Carlota; Pemán, Javier; Viasus, Diego; Ayats, Josefina; Carratalà, Jordi

    2013-01-01

    Background Statins have immunomodulatory properties and hinder Candida growth. However, it is unknown whether they may improve prognosis in patients with candidemia. We sought to determine the effect of prior statin use on the clinical outcomes of patients suffering candidemia. Methods and Findings Multicenter cohort study of hospitalized adults with candidemia between 2005 and 2011 in six hospitals in Spain, Brazil and Argentina. Of 326 candidemias, 44 (13.5%) occurred in statin users and 282 (86.5%) in statin non-users. The median value of APACHE II at candidemia diagnosis was similar between groups (18 vs. 16; p=.36). Candida albicans was the most commonly isolated species, followed by C. parapsilosis, C. tropicalis, C. glabrata, and C. krusei. There were no differences regarding appropriate empirical antifungal treatment. Statin users had a lower early (5 d) case-fatality rate than non-users (4.5 vs. 17%; p=.031). This effect was not observed with other cardiovascular drugs (aspirin, beta blockers and ACE inhibitors). Independent factor related to early case-fatality rate was APACHE II score (AOR, 1.08; 95% CI, 1.03–1.14; p=.002). An appropriate empirical antifungal therapy (AOR, 0.11; 95% CI, 0.04–0.26; p=statin use were independently associated with lower early case-fatality (AOR, 0.17; 95% CI, 0.03–0.93; p=.041). Fourteen days (14d) and overall (30d) case-fatality rates were similar between groups (27% vs. 29%; p=0.77 and 40% vs. 44%; p=.66). Conclusions The use of statins might have a beneficial effect on outcomes of patients with candidemia. This hypothesis deserves further evaluation in randomized trials. PMID:24155941

  19. Towards safe and effective CD38-CAR T cell therapy for myeloma

    NARCIS (Netherlands)

    Drent, Esther

    2018-01-01

    Immunotherapy is a promising field within cancer therapy. The recent progresses resulted in 'Immunotherapy for the treatment of cancer' as break-through of the year in 2013. This was partly due to the great successes with Chimeric Antigen Receptor (CAR) T cell therapy. With CAR T cells, recognition

  20. Statins and Risk of New-Onset Diabetes Mellitus

    Science.gov (United States)

    ... if you have or are at risk for diabetes mellitus. What Does This US Food and Drug Administration Advisory Mean to Me? ... Cause Diabetes Mellitus? What If I Already Have Diabetes? Will Statin Therapy Make It Worse? What Does This US Food and Drug Administration Advisory Mean to Me? ...

  1. Cognitive and Physical Function by Statin Exposure in Elderly Individuals Following Acute Myocardial Infarction.

    Science.gov (United States)

    Swiger, Kristopher J; Martin, Seth S; Tang, Fengming; Blaha, Michael J; Blumenthal, Roger S; Alexander, Karen P; Arnold, Suzanne V; Spertus, John A

    2015-08-01

    Despite beneficial effects on morbidity and mortality after acute myocardial infarction (AMI), concerns remain about the safety of statin therapy, particularly their potential effects on cognitive and physical function, in elderly individuals. Among statin-naive AMI patients age ≥ 65 years in a multicenter US registry, we examined the association between statin prescription at discharge and change in cognition (via Modified Telephone Interview for Cognitive Status [TICS-M]) assessed at 1 and 6 months after AMI. Short Form-12 Physical Component score, hand grip, walk time, and chair-rise tests were used to assess physical function. We conducted noninferiority testing to evaluate the hypothesis that the mean change in cognitive function was no worse among patients recently started on statins compared with those who were not. Among 317 elderly AMI patients, 262 patients (83%) were prescribed a statin at discharge and 55 were not. After matching for propensity to be discharged on statin after AMI, the effect of statin treatment on change in TICS-M from 1 to 6 months (estimated difference, 0.11 points; 95% confidence interval: -2.11 to 2.32, P = 0.92) showed noninferiority (inferiority threshold 3 points). There were no significant differences in any physical function measure. Among statin-naive elderly individuals recovering from AMI, initiation of statin therapy was not associated with detectable changes in short-term cognitive or physical function. These findings support the general safety of statin therapy for secondary prevention in this population. © 2015 Wiley Periodicals, Inc.

  2. Statins: Do They Cause ALS?

    Science.gov (United States)

    ... muscles needed to move, speak, eat and breathe. Statins are medications prescribed for the treatment of high cholesterol. These medications can sometimes cause muscle pain (myalgia), muscle weakness or, very rarely, severe muscle ...

  3. Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy

    DEFF Research Database (Denmark)

    Kirk, Ole; Reiss, Peter; Uberti-Foppa, Caterina

    2002-01-01

    maintenance therapy for cytomegalovirus (CMV) end-organ disease, disseminated Mycobacterium avium complex (MAC) infection, cerebral toxoplasmosis, and extrapulmonary cryptococcosis in patients receiving antiretroviral therapy. DESIGN: Observational study. SETTING: Seven European HIV cohorts. PATIENTS: 358...... identified: 162 for CMV disease, 103 for MAC infection, 75 for toxoplasmosis, and 39 for cryptococcosis. During 781 person-years of follow-up, five patients had relapse. Two relapses (one of CMV disease and one of MAC infection) were diagnosed after maintenance therapy was interrupted when the CD4 lymphocyte....... One relapse (toxoplasmosis) was diagnosed after maintenance therapy interruption at a CD4 lymphocyte count greater than 200 x 10(6) cells/L for 15 months. The overall incidences of recurrent CMV disease, MAC infection, toxoplasmosis, and cryptococcosis were 0.54 per 100 person-years (95% CI, 0.07 to 1...

  4. Treatment and Response to Statins: Gender-related Differences.

    Science.gov (United States)

    Raparelli, Valeria; Pannitteri, Gaetano; Todisco, Tommaso; Toriello, Filippo; Napoleone, Laura; Manfredini, Roberto; Basili, Stefania

    2017-01-01

    Response to drug administration is a primary determinant for treatment success. Sex and gender disparities play a role in determining the efficacy and safety of the most commonly used medications suggesting the need for a sex-tailored approach in prescription. Statins are a cost-effective strategy for cardiovascular disease (CVD) prevention. While statins are similarly effective in secondary CVD prevention, some concerns raised by conflicting data reported in primary CVD prevention clinical trials. The small representation of women in clinical trials and the fewer rates of events due to the lower female baseline CVD risk may have conditioned contradictory meta-analysis findings. Specifically, benefits outweigh disadvantages of statin therapy in women with a high CVD risk, while several doubts exist for the primary prevention of women at low-intermediate CVD risk. Furthermore, disparities between women and men in medication adherence may influence statin efficacy in CVD prevention. The sex-dependent impact of adverse side effects is one of the reasons advocated for explaining the gender gap, but it is not evidence-proved. The present review summarizes the sex and gender differences in the use of statins, pointing out new perspectives and opening issues in sex-tailored CVD prevention strategy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Impact of the JUPITER trial on statin prescribing for primary prevention.

    Science.gov (United States)

    Teng, Jennifer F T; Gomes, Tara; Camacho, Ximena; Grundy, Scott; Juurlink, David N; Mamdani, Muhammad M

    2014-01-01

    As the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial identified a new population of individuals with cholesterol levels below traditional treatment thresholds but with elevated high-sensitivity C-reactive protein (hs-CRP) levels who may benefit from primary prevention with statin therapy, we sought to evaluate the impact of this trial on the incident prescription rates of rosuvastatin alone as well as all statins in a primary prevention population. Population-based, cross-sectional time-series analysis. Administrative health care databases in Ontario, Canada. A total of 299,809 incident statin users 66 years or older were identified during the study period, from January 1, 2003, to March 31, 2011, who were prescribed statin therapy for primary prevention. We evaluated the incident rate of rosuvastatin and all statin use during each quarter of the study period. Overall, no significant trends in all incident statin use were observed (p=0.99). Furthermore, no significant differences were observed in incident rates of rosuvastatin (p=0.21) or all statin (p=0.41) use after the publication of the JUPITER trial. Despite the lack of impact of the JUPITER trial on rosuvastatin or all statin utilization, the relative market share of rosuvastatin increased from 9% to 65% over the study period. The publication of the JUPITER trial did not significantly affect trends in overall statin and rosuvastatin prescribing patterns for primary prevention in this study. Increases in the relative market share of rosuvastatin may be attributed to the impact of the pharmaceutical industry on prescribing patterns. Our results highlight the need to further improve the integration of evidence-based prescribing into cost-effective clinical practice. © 2013 Pharmacotherapy Publications, Inc.

  6. Statins induce apoptosis in rat and human myotube cultures by inhibiting protein geranylgeranylation but not ubiquinone

    International Nuclear Information System (INIS)

    Johnson, Timothy E.; Zhang, Xiaohua; Bleicher, Kimberly B.; Dysart, Gary; Loughlin, Amy F.; Schaefer, William H.; Umbenhauer, Diane R.

    2004-01-01

    Statins are widely used to treat lipid disorders. These drugs are safe and well tolerated; however, in <1% of patients, myopathy and/or rhabdomyolysis can develop. To better understand the mechanism of statin-induced myopathy, we examined the ability of structurally distinct statins to induce apoptosis in an optimized rat myotube model. Compound A (a lactone) and Cerivastatin (an open acid) induced apoptosis, as measured by TUNEL and active caspase 3 staining, in a concentration- and time-dependent manner. In contrast, an epimer of Compound A (Compound B) exhibited a much weaker apoptotic response. Statin-induced apoptosis was completely prevented by mevalonate or geranylgeraniol, but not by farnesol. Zaragozic acid A, a squalene synthase inhibitor, caused no apoptosis on its own and had no effect on Compound-A-induced myotoxicity, suggesting the apoptosis was not a result of cholesterol synthesis inhibition. The geranylgeranyl transferase inhibitors GGTI-2133 and GGTI-2147 caused apoptosis in myotubes; the farnesyl transferase inhibitor FTI-277 exhibited a much weaker effect. In addition, the prenylation of rap1a, a geranylgeranylated protein, was inhibited by Compound A in myotubes at concentrations that induced apoptosis. A similar statin-induced apoptosis profile was seen in human myotube cultures but primary rat hepatocytes were about 200-fold more resistant to statin-induced apoptosis. Although the statin-induced hepatotoxicity could be attenuated with mevalonate, no effect was found with either geranylgeraniol or farnesol. In studies assessing ubiquinone levels after statin treatment in rat and human myotubes, there was no correlation between ubiquinone levels and apoptosis. Taken together, these observations suggest that statins cause apoptosis in myotube cultures in part by inhibiting the geranylgeranylation of proteins, but not by suppressing ubiquinone concentration. Furthermore, the data from primary hepatocytes suggests a cell-type differential

  7. Statin Treatment and Mortality in Bacterial Infections – A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Björkhem-Bergman, Linda; Bergman, Peter; Andersson, Jan; Lindh, Jonatan D.

    2010-01-01

    Background Several studies have reported improved survival in severe bacterial infections among statin treated patients. In addition, statins have been ascribed beneficial anti-inflammatory effects. The aim of this study was to evaluate the effect of statin-treatment on mortality in patients with bacterial infections, by means of a systematic review and a meta-analysis. Methodology and Principal Findings Studies investigating the association between statin use and mortality in patients with bacterial disease were identified in a systematic literature review and a meta-analysis was performed to calculate the overall odds ratio of mortality in statin users. The literature search identified 947 citations from which 40 relevant studies were extracted. In all, 15 studies comprising 113 910 patients were included in the final analysis. Statin use was associated with a significantly (pstatin treatment was no longer significant, with an OR of 0.79 (95% CI 0.58–1.07). Conclusion/Significance According to the meta-analysis of observational studies presented here, patients on statin therapy seem to have a better outcome in bacterial infections. However, the association did not reach statistical significance after adjustment for apparent publication bias. Thus, there is a great need for randomised controlled trials investigating the possible beneficial effect of statins in bacterial infections. PMID:20502712

  8. Increasing incidence of statin treatmentamong the elderly and those withoutprevious cardiovascular conditions. A nationwide register study

    DEFF Research Database (Denmark)

    Kildemoes, Helle Wallach; Andersen, Morten

      Background: Supported by the growing evidence of the beneficial effects of statins in a range of conditions, statin utilization has increased considerably in most Western countries over the last decade. Objectives: To estimate to what extent a widening of indication scope for statins accounts...... with discharge diagnoses and surgical procedures performed during 1977-2005. The disease status for all cohort members was assigned by means of disease markers for seven cardiovascular conditions, corresponding to a hierarchy of broad indications for statin therapy. Using the indication hierarchy, we computed...

  9. Lipid-lowering therapy: who can benefit?

    Science.gov (United States)

    Lewis, Sandra J

    2011-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the US. Despite the decline in CVD-associated mortality rates in recent years, coronary heart disease (CHD) still causes one in every six deaths in this country. Because most CHD risk factors are modifiable (eg, smoking, hypertension, obesity, onset of type 2 diabetes, and dyslipidemia), cardiovascular risk can be reduced by timely and appropriate interventions, such as smoking cessation, diet and lifestyle changes, and lipid-modifying therapy. Dyslipidemia, manifested by elevated low-density lipoprotein cholesterol (LDL-C), is central to the development and progression of atherosclerosis, which can be silent for decades before triggering a first major cardiovascular event. Consequently, dyslipidemia has become a primary target of intervention in strategies for the prevention of cardiovascular events. The guidelines of the Adult Treatment Panel (ATP) III, updated in 2004, recommend therapeutic lifestyle changes and the use of lipid-lowering medications, such as statins, to achieve specific LDL-C goals based on a person's global cardiovascular risk. For high-risk individuals, such as patients with CHD and diabetic patients without CHD, an LDL-C target of < 100 mg/dL is recommended, and statin therapy should be considered to help patients achieve this goal. If correctly dosed in appropriate patients, currently approved statins are generally safe and provide significant cardiovascular benefits in diverse populations, including women, the elderly, and patients with diabetes. A recent primary prevention trial also showed that statins benefit individuals traditionally not considered at high risk of CHD, such as those with no hyperlipidemia but elevated C-reactive protein. Additional evidence suggests that statins may halt or slow atherosclerotic disease progression. Recent evidence confirms the pivotal role of statins in primary and secondary prevention.

  10. On the safe use of verify-and-record systems in external beam radiation therapy

    International Nuclear Information System (INIS)

    Seelantag, W.W.; Davis, J.B.

    1997-01-01

    Verify-and-record (V and R) systems are being used increasingly, not only for verification, but also for computer aided setup and chart printing. The close intercorrelation between V and R system and treatment routine requires new ideas for quality assurance (QA): pure ''machine checking'' as with treatment units is not sufficient anymore. The level of QA obviously depends on the tasks of the V and R system: the most advanced case of the system being used for computer aided setup and for chart printing is discussed -both are indispensable for an efficient use of V and R systems. Seven propositions are defined to make this not only efficient but safe. (author)

  11. Safe Oral Triiodo-L-Thyronine Therapy Protects from Post-Infarct Cardiac Dysfunction and Arrhythmias without Cardiovascular Adverse Effects.

    Directory of Open Access Journals (Sweden)

    Viswanathan Rajagopalan

    Full Text Available A large body of evidence suggests that thyroid hormones (THs are beneficial for the treatment of cardiovascular disorders. We have shown that 3 days of triiodo-L-thyronine (T3 treatment in myocardial infarction (MI rats increased left ventricular (LV contractility and decreased myocyte apoptosis. However, no clinically translatable protocol is established for T3 treatment of ischemic heart disease. We hypothesized that low-dose oral T3 will offer safe therapeutic benefits in MI.Adult female rats underwent left coronary artery ligation or sham surgeries. T3 (~6 μg/kg/day was available in drinking water ad libitum immediately following MI and continuing for 2 month(s (mo. Compared to vehicle-treated MI, the oral T3-treated MI group at 2 mo had markedly improved anesthetized Magnetic Resonance Imaging-based LV ejection fraction and volumes without significant negative changes in heart rate, serum TH levels or heart weight, indicating safe therapy. Remarkably, T3 decreased the incidence of inducible atrial tachyarrhythmias by 88% and improved remodeling. These were accompanied by restoration of gene expression involving several key pathways including thyroid, ion channels, fibrosis, sympathetic, mitochondria and autophagy.Low-dose oral T3 dramatically improved post-MI cardiac performance, decreased atrial arrhythmias and cardiac remodeling, and reversed many adverse changes in gene expression with no observable negative effects. This study also provides a safe and effective treatment/monitoring protocol that should readily translate to humans.

  12. Adoptive T cell Therapy Against Solid Tumors: Success Requires Safe TCRs and Countering Immune Evasion

    NARCIS (Netherlands)

    A. Kunert (Andre)

    2018-01-01

    textabstractImmune therapy has proven its feasibility in cancer treatment and in some cases even its preeminence over other treatment modalities such as chemotherapy. Despite promising results observed in clinical trials utilizing or targeting various components of the patient’s own immune system,

  13. Controversial issue: is it safe to employ mesenchymal stem cells in cell-based therapies?

    DEFF Research Database (Denmark)

    Lepperdinger, Günter; Brunauer, Regina; Jamnig, Angelika

    2008-01-01

    The prospective clinical use of multipotent mesenchymal stromal stem cells (MSC) holds enormous promise for the treatment of a large number of degenerative and age-related diseases. However, the challenges and risks for cell-based therapies are multifaceted. The risks for patients receiving stem ...

  14. Drug-drug Interactions of Statins Potentially Leading to Muscle-Related Side Effects in Hospitalized Patients.

    Science.gov (United States)

    Bucsa, Camelia; Farcas, Andreea; Leucuta, D; Mogosan, Cristina; Bojita, M; Dumitrascu, D L

    2015-01-01

    The associations of drugs that may interact with the statins resulting in elevated serum concentration of the statins are an important risk factor for statin induced muscle disorders. We aimed to determine the prevalence of these associations in all hospitalized patients that had been prescribed statins before/during hospitalization and to find out how often they are associated with muscle-related side effects. This prospective, non-interventional study performed in two internal medicine departments included patients with statin therapy before/during hospitalization. Data on each patient demographic characteristics, co-morbidities and treatment was collected from medical charts and interviews. We evaluated patients' therapy for the targeted associations using Thomson Micromedex Drug Interactions checker and we ranked the identified drug-drug interactions (DDIs) accordingly. Each patient with statin treatment before admission was additionally interviewed in order to identify muscular symptoms. In 109 patients on statin treatment we found 35 potential (p) DDIs of statins in 30 (27.5%) patients, most of which were in the therapy before admission (27 pDDIs). The pDDIs were moderate (20 pDDIs) and major (15 pDDIs). Of the total number of pDDIs, 24 were targeting the muscular system. The drugs most frequently involved in the statins' pDDIs were amiodarone and fenofibrate. Two of the patients with pDDIs reported muscle pain, both having additional risk factors for statin induced muscular effects. The prevalence of statins' pDDIs was high in our study, mostly in the therapy before admission, with only a small number of pDDIs resulting in clinical outcome.

  15. Is Endoscopic Therapy Safe for Upper Gastrointestinal Bleeding in Anticoagulated Patients With Supratherapeutic International Normalized Ratios?

    Science.gov (United States)

    Shim, Choong Nam; Chung, Hyun Soo; Park, Jun Chul; Shin, Sung Kwan; Lee, Sang Kil; Lee, Yong Chan; Kim, Ha Yan; Kim, Dong Wook; Lee, Hyuk

    2016-01-01

    The management of upper gastrointestinal bleeding (UGIB) in anticoagulated patients with supratherapeutic international normalized ratios (INRs) presents a challenge. The purpose of the study was to evaluate the safety of endoscopic therapy for UGIB in anticoagulated patients with supratherapeutic INR in terms of rebleeding and therapeutic outcomes. One hundred ninety-two anticoagulated patients who underwent endoscopic treatment for UGIB were enrolled in the study. Patients were divided into 2 groups based on the occurrence of rebleeding within 30 days of the initial therapeutic endoscopy: no-rebleeding group (n = 168) and rebleeding group (n = 24). The overall rebleeding rate was 12.5%. Bleeding from gastric cancer and bleeding at the duodenum were significantly related to rebleeding in a univariate analysis. Multivariate analysis determined that presenting symptoms other than melena (hematemesis, hematochezia, or others) (odds ratio, 3.93; 95% confidence interval, 1.44-10.76) and bleeding from gastric cancer (odds ratio, 6.10; 95% confidence interval, 1.27-29.25) were significant factors predictive of rebleeding. Supratherapeutic INR at the time of endoscopic therapy was not significantly associated with rebleeding in either univariate or multivariate analysis. Significant differences in bleeding-related mortality, additional intervention to control bleeding, length of hospital stay, and transfusion requirements were revealed between the rebleeding and no-rebleeding groups. There were no significant differences in therapeutic outcomes between patients with INR within the therapeutic range and those with supratherapeutic INR. Supratherapeutic INR at the time of endoscopic therapy did not change rebleeding and therapeutic outcomes. Thus, we should consider endoscopic therapy for UGIB in anticoagulated patients, irrespective of INR at the time of endoscopic therapy.

  16. Quality of life, anxiety and concerns among statin-treated children with familial hypercholesterolaemia and their parents

    NARCIS (Netherlands)

    de Jongh, S.; Kerckhoffs, M. C.; Grootenhuis, M. A.; Bakker, H. D.; Heymans, H. S. A.; Last, B. F.

    2003-01-01

    Aim: To assess the quality of life, anxiety and concerns among statin-treated children with familial hypercholesterolaemia (FH) and their parents. Methods: 69 FH children on statin therapy and 87 parents (51 families) participated in this study. Quality of life of the children, and anxiety levels of

  17. INTEGRATED ASSESSMENT OF STATIN-ASSOCIATED MUSCLE DAMAGE PREDICTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. I. Petrov

    2015-09-01

    Full Text Available Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months, р<0.0001 and in higher doses, than patients without muscle pain/weakness. There were not significant differences in creatine kinase levels between patients with and without muscle symptoms. Patients with SLCO1B1*5 genotype were revealed in both groups, but more often (58% among patients with muscle symptoms. Patients with abnormal C allele having muscle symptoms received statins significantly longer, than these without muscle signs (54.7 vs 13.9 months, р=0.0028.Conclusion. Association between occurrence of muscle symptoms and SLCO1B1*5 allele carriership, statin dose and therapy duration was revealed. Creatine kinase examination was not valuable for finding of statin-induced muscle damage.

  18. INTEGRATED ASSESSMENT OF STATIN-ASSOCIATED MUSCLE DAMAGE PREDICTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE

    Directory of Open Access Journals (Sweden)

    V. I. Petrov

    2013-01-01

    Full Text Available Aim. To assess the risk factors of statin-associated muscle damage in patient with ischemic heart disease.Material and methods. 258 patients with ischemic heart disease treated with statin were included into the study. Total plasma creatine kinase levels were measured and SLCO1B1*5 genotyping was performed. Relationship between statin therapy and adverse events was evaluated by Naranjo algorithm.Results. Patients with muscle symptoms received statins significantly longer (48.8 vs 11.9 months, р<0.0001 and in higher doses, than patients without muscle pain/weakness. There were not significant differences in creatine kinase levels between patients with and without muscle symptoms. Patients with SLCO1B1*5 genotype were revealed in both groups, but more often (58% among patients with muscle symptoms. Patients with abnormal C allele having muscle symptoms received statins significantly longer, than these without muscle signs (54.7 vs 13.9 months, р=0.0028.Conclusion. Association between occurrence of muscle symptoms and SLCO1B1*5 allele carriership, statin dose and therapy duration was revealed. Creatine kinase examination was not valuable for finding of statin-induced muscle damage.

  19. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    Science.gov (United States)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  20. Pre-hemorrhage statin use and the risk of vasospasm following aneurysmal subarachnoid hemorrhage

    Science.gov (United States)

    Moskowitz, Shaye I.; Ahrens, Christine; Provencio, J Javier; Chow, Michael; Rasmussen, Peter A

    2010-01-01

    Background and Purpose Aneurysmal subarachnoid hemorrhage (SAH) is often followed by delayed ischemic deficits attributable to cerebral vasospasm. Recent studies suggest a positive impact of statin therapy on the incidence of vasospasm. This study was designed to assess whether a history of prior use of statin therapy was associated with a lower risk of vasospasm in patients with SAH. Methods We performed a comprehensive retrospective review of patients with aneurysmal SAH between 1997 and 2004. Clinical demographics and imaging data for all patients were reviewed and a logistic regression analysis was performed to identify the predictors of cerebral vasospasm, defined as a combination of clinical signs with radiographic confirmation. Results 308 patients were included. Mean age was higher in the group receiving statins (64 +/- 12 versus 54+/- 12 years). Hunt and Hess scores and treatment modality were not significantly different between the groups. Vasospasm was observed in 31% of patients not taking a statin (n=282) versus 23% taking a statin (n=26), without achieving statistical significance. Discontinuation of the statin did not affect risk of vasospasm. Conclusions Use of a statin prior to an aneurysmal SAH trended to reduce the incidence of subsequent vasospasm, without achieving statistical significance. PMID:18423529

  1. Statin precipitated lactic acidosis?

    Science.gov (United States)

    Neale, R; Reynolds, T M; Saweirs, W

    2004-09-01

    An 82 year old woman was admitted with worsening dyspnoea. Arterial blood gases were taken on air and revealed a pH of 7.39, with a partial pressure of CO2 (pCO2) of 1.2 kPa, pO2 of 19.3 kPa, HCO3 of 13.8 mmol/litre, and base excess of -16.3 mmol/litre: a compensated metabolic acidosis with hyperventilation induced hypocapnia, which is known to be a feature of lactic acidosis. There was also an increased anion gap ((Na140 + K4.0) - (Cl 106 + HCO3 13.8) = 24.2 mEq/litre (reference range, 7-16)), consistent with unmeasured cation. Lactate was measured and found to be raised at 3.33 mmol/litre (reference range, 0.9-1.7). After exclusion of common causes of lactic acidosis Atorvastatin was stopped and her acid-base balance returned to normal. Subsequently, thiamine was also shown to be deficient. The acidosis was thought to have been the result of a mitochondrial defect caused by a deficiency of two cofactors, namely: ubiquinone (as a result of inhibition by statin) and thiamine (as a result of dietary deficiency).

  2. Statin use and Parkinson's disease in Denmark

    DEFF Research Database (Denmark)

    Ritz, Beate; Manthripragada, Angelika D; Qian, Lei

    2010-01-01

    diagnosis. Employing logistic regression adjusting for age, sex, diagnosis of chronic obstructive pulmonary disease, and Charlson comorbidity, we observed none to slightly inverse associations between PD diagnosis and statin prescription drug use. Inverse associations with statin use were only observed...

  3. Mass media and GP statin prescribing.

    NARCIS (Netherlands)

    Verheij, R.A.; Kleijer, S.J.; Dijk, L. van; Schellevis, F.G.

    2009-01-01

    Background: In March 2007, a Dutch consumer affairs television programme (Radar) questioned the effectiveness of statins in reducing mortality and cardiovascular incidents. We investigated the effects of this television broadcasting on statin prescriptions by GPs in people with and without

  4. Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study.

    Science.gov (United States)

    Kaasenbrood, Lotte; Poulter, Neil R; Sever, Peter S; Colhoun, Helen M; Livingstone, Shona J; Boekholdt, S Matthijs; Pressel, Sara L; Davis, Barry R; van der Graaf, Yolanda; Visseren, Frank L J

    2016-05-01

    In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was 4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]). ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that may complement informed decision making. URL: http

  5. Understanding Statin Use in America and Gaps in Patient Education (USAGE): an internet-based survey of 10,138 current and former statin users.

    Science.gov (United States)

    Cohen, Jerome D; Brinton, Eliot A; Ito, Matthew K; Jacobson, Terry A

    2012-01-01

    Statins substantially reduce the risk of cardiovascular disease and are generally well-tolerated. Despite this, many patients discontinue therapy. A better understanding of the characteristics of current and former statin users may be helpful for formulating strategies to improve long-term adherence. The Understanding Statin Use in America and Gaps in Education (USAGE) survey assessed the attitudes, beliefs, practices, and behavior of current and former statin users. Individuals 18 years or older who reported a history of high cholesterol and current or former statin use were identified within a registered consumer panel cohort in the United States and invited to participate in an Internet survey. Of the 10,138 respondents, 8918 (88%) were current statin users and 1220 (12%) were former users. Participants (mean age 61 years) were predominantly white (92%), female (61%), of middle income (median $44,504/yr), and had health insurance (93%). Among current users, 95% took a statin alone, and 70% had not missed a dose in the past month. Although ∼70% reported that their physicians had explained the importance of cholesterol levels for their heart health former users were less satisfied with the discussions (65% vs. 83%, P users, respectively (P users was cost (32%) and the primary reason for discontinuation was side effects (62%). This survey provides important insights into behavior and attitudes among current and former statin users and the results suggest that more effective dialogue between healthcare providers and patients may increase persistence of statin use, particularly when the patient has concerns about side effects and drug costs. Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  6. Use of statins and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, David; Andersen, L; Hallas, Jesper

    2013-01-01

    Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting.......Laboratory studies and a single case-control study have suggested a protective effect of statins on the risk of glioma. We wished to investigate the influence of statin use on the risk of glioma in a population-based setting....

  7. Statins and morbidity and mortality in COPD in the COMIC study: a prospective COPD cohort study.

    Science.gov (United States)

    Citgez, Emanuel; van der Palen, Job; Koehorst-Ter Huurne, Kirsten; Movig, Kris; van der Valk, Paul; Brusse-Keizer, Marjolein

    2016-01-01

    Both chronic inflammation and cardiovascular comorbidity play an important role in the morbidity and mortality of patients with chronic obstructive pulmonary disease (COPD). Statins could be a potential adjunct therapy. The additional effects of statins in COPD are, however, still under discussion. The aim of this study is to further investigate the association of statin use with clinical outcomes in a well-described COPD cohort. 795 patients of the Cohort of Mortality and Inflammation in COPD (COMIC) study were divided into statin users or not. Statin use was defined as having a statin for at least 90 consecutive days after inclusion. Outcome parameters were 3-year survival, based on all-cause mortality, time until first hospitalisation for an acute exacerbation of COPD (AECOPD) and time until first community-acquired pneumonia (CAP). A sensitivity analysis was performed without patients who started a statin 3 months or more after inclusion to exclude immortal time bias. Statin use resulted in a better overall survival (corrected HR 0.70 (95% CI 0.51 to 0.96) in multivariate analysis), but in the sensitivity analysis this association disappeared. Statin use was not associated with time until first hospitalisation for an AECOPD (cHR 0.95, 95% CI 0.74 to 1.22) or time until first CAP (cHR 1.1, 95% CI 0.83 to 1.47). In the COMIC study, statin use is not associated with a reduced risk of all-cause mortality, time until first hospitalisation for an AECOPD or time until first CAP in patients with COPD.

  8. Strategy Escalation: An emerging paradigm for safe clinical development of T cell gene therapies

    Directory of Open Access Journals (Sweden)

    Junghans Richard

    2010-06-01

    Full Text Available Abstract Gene therapy techniques are being applied to modify T cells with chimeric antigen receptors (CARs for therapeutic ends. The versatility of this platform has spawned multiple options for their application with new permutations in strategies continually being invented, a testimony to the creative energies of many investigators. The field is rapidly expanding with immense potential for impact against diverse cancers. But this rapid expansion, like the Big Bang, comes with a somewhat chaotic evolution of its therapeutic universe that can also be dangerous, as seen by recently publicized deaths. Time-honored methods for new drug testing embodied in Dose Escalation that were suitable for traditional inert agents are now inadequate for these novel "living drugs". In the following, I propose an approach to escalating risk for patient exposures with these new immuno-gene therapy agents, termed Strategy Escalation, that accounts for the molecular and biological features of the modified cells and the methods of their administration. This proposal is offered not as a prescriptive but as a discussion framework that investigators may wish to consider in configuring their intended clinical applications.

  9. Statins in acute neurologic disease:which one, which dose, when to start, and when not to stop

    Institute of Scientific and Technical Information of China (English)

    Bong-Su Kang; Gene Sung; May Kim-Tenser; Nerses Sanossian

    2016-01-01

    Statins could have physiologic properties that may beneift patients that have been diagnosed with various acute neurological diseases. This review aims tosummarize the literature pertaining to stain use in acute neurological disease such as subarachnoid hemorrhage, intracerebral hemorrhage (ICH), cerebral ischemia (CI), traumatic brain injury, status epilepticus and meningitis. The authors reviewed published abstracts and manuscripts pertaining to experimental and clinical trials relevant to statins in acute neurological disease. Although acute statin therapy in the setting of subarachnoid hemorrhage might reduce delayed cerebral ischemia and mortality, it should not be considered standard care at this time. Acute statins therapy has not demonstrated anybeneift yet folowing an ICH or CI. Acute statin withdrawal may worsen outcome in acute CI. Observational and case-control studies suggest that pretreatment with statin at time of onset may be associated with better outcomes. Even though preclinical studies have shown statins to have beneifcial effects, there has been no clinical evidence. In conclusion, current published studies have not shown that acute statin therapy has any beneifcal effects in acute neurologic diseases and therefore further large randomized clinical trials are needed.

  10. LIFESTAT – Living with statins

    DEFF Research Database (Denmark)

    Christensen, Christa Lykke; Helge, Jørn Wulff; Krasnik, Allan

    2016-01-01

    AIM: LIFESTAT is an interdisciplinary project that leverages approaches and knowledge from medicine, the humanities and the social sciences to analyze the impact of statin use on health, lifestyle and well-being in cohorts of Danish citizens. The impetus for the study is the fact that 10....... The study investigates the biological consequences of statin treatment; determines the mechanism(s) by which statin use causes muscle and mitochondrial dysfunction; and analyzes achievement of treatment goals, people's perception of disease risk, media influence on people's risk and health perception...... and unintended side effects (e.g. myalgia, and glucose and exercise intolerance). METHODS: The LIFESTAT project combines invasive human experiments, biomedical analyses, nationwide surveys, epidemiological studies, qualitative interviews, media content analyses, and ethnographic participant observations...

  11. The effect of statins on cardiovascular outcomes by smoking status: A systematic review and meta-analysis of randomized controlled trials

    NARCIS (Netherlands)

    Ursoniu, Sorin; Mikhailidis, Dimitri P.; Serban, Maria-Corina; Penson, Peter; Toth, Peter P.; Ridker, Paul M.; Ray, Kausik K.; Kees Hovingh, G.; Kastelein, John J.; Hernandez, Adrian V.; Manson, JoAnn E.; Rysz, Jacek; Banach, Maciej

    2017-01-01

    Smoking is an important risk factor for cardiovascular disease (CVD) morbidity and mortality. The impact of statin therapy on CVD risk by smoking status has not been fully investigated. Therefore we assessed the impact of statin therapy on CVD outcomes by smoking status through a systematic review

  12. Stroke and the Cell Therapy Saga: Towards a Safe, Swift and Efficient Utilization of cells.

    Science.gov (United States)

    Kubis, Nathalie

    2017-01-01

    The first clinical trials of cell therapy in stroke were first published in the 2000s and consisted of neural stems cells transplanted via the intracerebral pathway. Since mesenchymal stem cells showed similar capacities to differentiate into neural cells and allowed autologous cell transplantation, they were then preferentially studied, including diabetes and hypertension. More recently, bone marrow derived mononuclear cells were successfully transplanted in stroke with no need of culture processing, and simple collection by density gradient centrifugation rendering them immediately ready for use. They improve post-stroke neurological deficit in rodents and clinical trials have shown the feasibility of intra-arterial or intravenous administration. The underlying mechanisms are not yet understood. We investigated the therapeutic potential of peripheral blood derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+). We showed that intravenously injected PB-MNC+ after cerebral ischemia reduced infarct volume at day 3, increased cell proliferation in the peri-infarct area and the subventricular zone, decreased microglial cell density, and upregulated TGF-β expression. At D14, microvessel density was increased and functional recovery enhanced, whereas plasma levels of BDNF were increased in treated mice. Ephrin-B2 induced phenotype switching of PB-MNC by upregulating genes controlling cell proliferation, inflammation and angiogenesis, as confirmed by adhesion and Matrigel assays. PB-MNC+ transplantation in stroke is a promising approach and should be investigated for the development of rapid, non-invasive bedside cell therapy strategies in stroke.(Presented at the 1944th Meeting, July 19, 2017).

  13. Improved outcome after primary vitrectomy in diabetic patients treated with statins.

    Science.gov (United States)

    Tuuminen, Raimo; Sahanne, Sari; Haukka, Jari; Loukovaara, Sirpa

    2016-01-01

    To evaluate the effect of preoperative statin treatment on the outcome of primary vitrectomy in type 1 and 2 diabetic patients. In this open, observational institutional study, a total of 192 eyes of 171 type 1 and 2 adult diabetic patients admitted for primary vitrectomy for management of sight-threatening forms of diabetic retinopathy were divided according to the use of lipid-lowering therapy: those with statin treatment (79 eyes of 73 patients) and those taking no statin medication (113 eyes of 98 patients). One-month best-corrected visual acuity (BCVA) gain and cumulative 12-month revitrectomy frequency were analyzed. In multivariate linear regression, diabetic patients with statin treatment had a better 1-month BCVA improvement than did those without statin treatment (absolute difference 0.26, 95% confidence interval [CI] 0.02-0.50, p = 0.028). Subgroup analysis revealed that diabetic patients on statin had better postoperative BCVA improvement when preoperative status included partial or panretinal laser photocoagulation (p = 0.042 and p = 0.049) and anti-vascular endothelial growth factor therapy (p = 0.011). Moreover, diabetic patients with preoperative macular edema (p = 0.009), vitreous hemorrhage (p<0.001), proliferative retinopathy (p<0.001), or tractional retinal detachment (p = 0.010) had better BCVA recovery if receiving statin. In Cox proportional hazards regression model, revitrectomies in our 12-month follow-up were less frequent in diabetic patients on statin treatment (hazard ratio 0.28, 95% CI 0.08-0.93, p = 0.037). These data provide novel insight into the potential clinical benefit for patients with sight-threatening diabetic retinopathy undergoing vitrectomy treated with statin.

  14. 45. Ezetimibe and statins yields on silent holter ambulatory myocardial ischemia

    Directory of Open Access Journals (Sweden)

    W. Kadro

    2016-07-01

    Full Text Available Further cholestrol lowering may affect silent ischemia detected on holter monitoring. Cholesterol lowering is associated with a reduction in cardiovascular morbidity and mortality. Statins are the main drugs for cholesterol lowering. Ezetimibe when added to statins gives further reduction in cholesterol but its long-term effect on cardiovascular morbidity and mortality and ischemic events is not known. This study sought to determine whether further cholesterol lowering with ezitimibe will also results in a reduction of myocardial ischemia during daily life. We enrolled 50 patients with proven stable coronary artery disease (CAD and at least one episode of ST-segment depression on ambulatory ECG monitoring. All of them were receiving optimal therapy for CAD including statin therapy for cholesterol reduction. 25 patients were randomized to continue their statin therapy (Statin only group and 25 to recieve statin plus ezitimibe 10 mg/day (ezitimibe group. Serum cholesterol and LDL cholesterol levels and ambulatory monitoring were repeated after 4–6 months of therapy. The two groups were comparable with respect to baseline characteristics, number of episodes of ST-segment depression, and baseline serum cholesterol levels. The ezitimibe group had lower mean total and LDL cholesterol levels at study end and experienced a significant reduction in the number of episodes of ST-segment depression compared with the statin only group. ST-segment depression was completely resolved in 13 of 25 patients (52% in the ezitimibe group versus 3 of 25 (12% in the statin only group. The ezitimibe group exhibited a highly significant reduction in ambulatory ischemia (P < .001. By logistic regression, treatment with ezitimibe was an independent predictor of ischemia resolution. Further cholesterol lowering with ezitimibe can result in reduction or resolution of myocardial ischemia recorded as episodes of ST-segment depression in ambulatory monitoring of the ECG.

  15. Does Googling lead to statin intolerance?

    Science.gov (United States)

    Khan, Sarah; Holbrook, Anne; Shah, Baiju R

    2018-07-01

    The nocebo effect, where patients with expectations of adverse effects are more likely to experience them, may contribute to the high rate of statin intolerance found in observational studies. Information that patients read on the internet may be a precipitant of this effect. The objective of the study was to establish whether the number of websites about statin side effects found using Google is associated with the prevalence of statin intolerance. The prevalence of statin intolerance in 13 countries across 5 continents was established in a recent study via a web-based survey of primary care physicians and specialists. Using the Google search engine for each country, the number of websites about statin side effects was determined, and standardized to the number of websites about statins overall. Searches were restricted to pages in the native language, and were conducted after connecting to each country using a virtual private network (VPN). English-speaking countries (Australia, Canada, UK, USA) had the highest prevalence of statin intolerance and also had the largest standardized number of websites about statin side effects. The sample Pearson correlation coefficient between these two variables was 0.868. Countries where patients using Google are more likely to find websites about statin side effects have greater levels of statin intolerance. The nocebo effect driven by online information may be contributing to statin intolerance. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Safe sex

    Science.gov (United States)

    ... sex; Sexually transmitted - safe sex; GC - safe sex; Gonorrhea - safe sex; Herpes - safe sex; HIV - safe sex; ... contact. STIs include: Chlamydia Genital herpes Genital warts Gonorrhea Hepatitis HIV HPV Syphilis STIs are also called ...

  17. Exploring association between statin use and breast cancer risk: an updated meta-analysis.

    Science.gov (United States)

    Islam, Md Mohaimenul; Yang, Hsuan-Chia; Nguyen, Phung-Anh; Poly, Tahmina Nasrin; Huang, Chih-Wei; Kekade, Shwetambara; Khalfan, Abdulwahed Mohammed; Debnath, Tonmoy; Li, Yu-Chuan Jack; Abdul, Shabbir Syed

    2017-12-01

    The benefits of statin treatment for preventing cardiac disease are well established. However, preclinical studies suggested that statins may influence mammary cancer growth, but the clinical evidence is still inconsistent. We, therefore, performed an updated meta-analysis to provide a precise estimate of the risk of breast cancer in individuals undergoing statin therapy. For this meta-analysis, we searched PubMed, the Cochrane Library, Web of Science, Embase, and CINAHL for published studies up to January 31, 2017. Articles were included if they (1) were published in English; (2) had an observational study design with individual-level exposure and outcome data, examined the effect of statin therapy, and reported the incidence of breast cancer; and (3) reported estimates of either the relative risk, odds ratios, or hazard ratios with 95% confidence intervals (CIs). We used random-effect models to pool the estimates. Of 2754 unique abstracts, 39 were selected for full-text review, and 36 studies reporting on 121,399 patients met all inclusion criteria. The overall pooled risks of breast cancer in patients using statins were 0.94 (95% CI 0.86-1.03) in random-effect models with significant heterogeneity between estimates (I 2  = 83.79%, p = 0.0001). However, we also stratified by region, the duration of statin therapy, methodological design, statin properties, and individual stain use. Our results suggest that there is no association between statin use and breast cancer risk. However, observational studies cannot clarify whether the observed epidemiologic association is a causal effect or the result of some unmeasured confounding variable. Therefore, more research is needed.

  18. Adherence to drug label recommendations for avoiding drug interactions causing statin-induced myopathy--a nationwide register study.

    Directory of Open Access Journals (Sweden)

    Jennifer Settergren

    Full Text Available To investigate the extent to which clinicians avoid well-established drug-drug interactions that cause statin-induced myopathy. We hypothesised that clinicians would avoid combining erythromycin or verapamil/diltiazem respectively with atorvastatin or simvastatin. In patients with statin-fibrate combination therapy, we hypothesised that gemfibrozil was avoided to the preference of bezafibrate or fenofibrate. When combined with verapamil/diltiazem or fibrates, we hypothesized that the dispensed doses of atorvastatin/simvastatin would be decreased.Cross-sectional analysis of nationwide dispensing data. Odds ratios of interacting erythromycin, verapamil/diltiazem versus respective prevalence of comparator drugs doxycycline, amlodipine/felodipine in patients co-dispensed interacting statins simvastatin/atorvastatin versus patients unexposed (pravastatin/fluvastatin/rosuvastatin was calculated. For fibrates, OR of gemfibrozil versus fenofibrate/bezafibrate in patients co-dispensed any statin was assessed.OR of interacting erythromycin versus comparator doxycycline did not differ between patients on interacting and comparator statins either in patients dispensed high or low statin doses (adjusted OR 0.87; 95% CI 0.60-1.25 and 0.92; 95% CI 0.69-1.23. Interacting statins were less common among patients dispensed verapamil/diltiazem as compared to patients on amlodipine/felodipine (OR high dose 0.62; CI 0.56-0.68 and low dose 0.63; CI 0.58-0.68. Patients on any statin were to a lesser extent dispensed gemfibrozil compared to patients not dispensed a statin (OR high dose 0.65; CI 0.55-0.76 and low dose 0.70; CI 0.63-0.78. Mean DDD (SD for any statin was substantially higher in patients co-dispensed gemfibrozil 178 (149 compared to patients on statin monotherapy 127 (93, (p<0.001.Prescribers may to some extent avoid co-prescription of statins with calcium blockers and fibrates with an increased risk of myopathy. We found no evidence for avoiding co

  19. Evaluation of skeletal muscle during calf exercise by 31-phosphorus magnetic resonance spectroscopy in patients on statin medications.

    Science.gov (United States)

    Wu, Jim S; Buettner, Catherine; Smithline, Howard; Ngo, Long H; Greenman, Robert L

    2011-01-01

    Muscle pain is a common side effect of statin medications, but the cause is poorly understood. We characterized phosphocreatine (PCr) exercise recovery kinetics in 10 patients with hypercholesterolemia before and after a 4-week regimen of statin therapy using 31-phosphorus magnetic resonance spectroscopy ((31) P-MRS). (31) P spectra were obtained before, during, and after exercise on a calf flexion pedal ergometer. Creatine kinase (CK) serum levels were drawn before and after statin therapy. The mean metabolic recovery time constant in subjects increased from 28.1 s (SE = 6.5 s) to 55.4 s (SE = 7.4 s) after statin therapy. The unweighted mean of the pre/post-recovery time difference was -27.3 s (SE = 12.4 s; P = 0.02). Pre- and post-therapy CK levels were not significantly different (P = 0.50). Metabolic recovery time in the calf is prolonged in patients after statin use. This suggests that statins impair mitochondrial oxidative function, and (31) P MRS is a potential study model for statin-associated myopathy. Copyright © 2010 Wiley Periodicals, Inc.

  20. Evaluation of skeletal muscle during calf exercise by 31P MR spectroscopy in patients on statin medications

    Science.gov (United States)

    Buettner, Catherine; Smithline, Howard; Ngo, Long H; Greenman, Robert L.

    2012-01-01

    Introduction Muscle pain is a common side effect of statin medications, however, the cause is poorly understood. Methods We characterized phosphocreatine (PCr) exercise recovery kinetics in 10 patients with hypercholesterolemia before and after a 4 week regimen of statin therapy using 31P magnetic resonance spectroscopy (31P-MRS). 31P spectra were obtained before, during, and following exercise on a calf flexion pedal ergometer. Creatine kinase (CK) serum levels were drawn before and after statin therapy. Results The mean metabolic recovery time constant in subjects increased from 28.1s (SE=6.5s) to 55.4s (SE=7.4s) following statin therapy. The unweighted mean of the pre-post recovery time difference was -27.3s (SE=12.4s); (p-value = 0.02). Pre- and post-therapy CK levels were not significantly different (p-value = 0.50). Discussion Metabolic recovery time in the calf is prolonged in patients following statin use. This suggests that statins impair mitochondrial oxidative function, and 31P –MRS is a potential study model for statin-associated myopathy. PMID:21171098

  1. MICROCIRCULATORY ISCHEMIA AND STATINS: LESSONS OF INTERVENTION CARDIOLOGY

    Directory of Open Access Journals (Sweden)

    An. A. Alexandrov

    2015-12-01

    Full Text Available Review is devoted to the pathogenesis of microcirculatory ischemia. Microcirculatory dysfunction has been identified in different groups of patients including syndrome X, diabetes mellitus 2 type, coronary heart disease. In coronary patients after transluminal angioplasty microcirculatory dysfunction is the reason of phenomenon of “non-reflow”. In result the procedure of revascularization is less effective. Therapy by statins can be beneficial for patients with microcirculatory ischemia.

  2. [Benefits and risks for primary prevention with statins in the elderly].

    Science.gov (United States)

    Joseph, Jean-Philippe; Afonso, Mélanie; Berdaï, Driss; Salles, Nathalie; Bénard, Antoine; Gay, Bernard; Bonnet, Fabrice

    2015-12-01

    Statins in primary prevention before 75 years old reduce cardiovascular events from 20 to 30% and mortality from 10% with acceptable side effects. We investigated whether these results persisted for patients aged 75 and older taking statin. Methodic review of large randomized clinical trials and meta-analyzes that included patients 75 years and older treated with statins in primary prevention. Since the 1990s, a score of randomized controlled trials studying statins versus placebo in primary prevention were published and studied in meta-analyses. Exclusion criteria, including persons older than 70 years, are often restrictive. The impact on all-cause mortality in the four main studies and meta-analyses in over 75 years has not been demonstrated. On the other hand, a recent meta-analyses of observational studies including subjects between 70 and 89 years treated with statins found that low total cholesterol was associated with a moderate decrease in cardiovascular mortality, with no decrease in all-cause mortality. Moreover, in a common context of comorbidities in this age group, statins may be responsible for many adverse effects, drug interactions and impaired quality of life. Given the lack of formal evidence of effectiveness in terms of all-cause mortality and a high level of adverse effects, the benefit/risk of primary prevention with statins is not established in the elderly. The economic weight of statin prescriptions and their possible impact on quality of life justify an economic analysis of discontinuing statin therapy for people 75 years and older. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Effect of statins on clinical and molecular responses to intramuscular interferon beta-1a.

    Science.gov (United States)

    Rudick, R A; Pace, A; Rani, M R S; Hyde, R; Panzara, M; Appachi, S; Shrock, J; Maurer, S L; Calabresi, P A; Confavreux, C; Galetta, S L; Lublin, F D; Radue, E-W; Ransohoff, R M

    2009-06-09

    Findings from a small clinical study suggested that statins may counteract the therapeutic effects of interferon beta (IFNbeta) in patients with relapsing-remitting multiple sclerosis (RRMS). We conducted a post hoc analysis of data from the Safety and Efficacy of Natalizumab in Combination With IFNbeta-1a in Patients With Relapsing-Remitting Multiple Sclerosis (SENTINEL) study to determine the effects of statins on efficacy of IFNbeta. SENTINEL was a prospective trial of patients with RRMS treated with natalizumab (Tysabri, Biogen Idec, Inc., Cambridge, MA) plus IM IFNbeta-1a (Avonex, Biogen Idec, Inc.) 30 microg compared with placebo plus IM IFNbeta-1a 30 microg. Clinical and MRI outcomes in patients treated with IM IFNbeta-1a only (no-statins group, n = 542) were compared with those of patients taking IM IFNbeta-1a and statins at doses used to treat hyperlipidemia (statins group, n = 40). No significant differences were observed between treatment groups in adjusted annualized relapse rate (p = 0.937), disability progression (p = 0.438), number of gadolinium-enhancing lesions (p = 0.604), or number of new or enlarging T2-hyperintense lesions (p = 0.802) at 2 years. More patients in the statins group reported fatigue, extremity pain, muscle aches, and increases in hepatic transaminases compared with patients in the no-statins group. Statin treatment had no ex vivo or in vitro effect on induction of IFN-stimulated genes. Statin therapy does not appear to affect clinical effects of IM interferon beta-1a in patients with relapsing-remitting multiple sclerosis or the primary molecular response to interferon beta treatment.

  4. Impact of statin adherence on cardiovascular disease and mortality outcomes: a systematic review

    Science.gov (United States)

    De Vera, Mary A; Bhole, Vidula; Burns, Lindsay C; Lacaille, Diane

    2014-01-01

    Aims While suboptimal adherence to statin medication has been quantified in real-world patient settings, a better understanding of its impact is needed, particularly with respect to distinct problems of medication taking. Our aim was to synthesize current evidence on the impacts of statin adherence, discontinuation and persistence on cardiovascular disease and mortality outcomes. Methods We conducted a systematic review of peer-reviewed studies using a mapped search of Medline, Embase and International Pharmaceutical Abstracts databases. Observational studies that met the following criteria were included: defined patient population; statin adherence exposure; defined study outcome [i.e. cardiovascular disease (CVD), mortality]; and reporting of statin-specific results. Results Overall, 28 studies were included, with 19 studies evaluating outcomes associated with statin adherence, six with statin discontinuation and three with statin persistence. Among adherence studies, the proportion of days covered was the most widely used measure, with the majority of studies reporting increased risk of CVD (statistically significant risk estimates ranging from 1.22 to 5.26) and mortality (statistically significant risk estimates ranging from 1.25 to 2.54) among non-adherent individuals. There was greater methodological variability in discontinuation and persistence studies. However, findings of increased CVD (statistically significant risk estimates ranging from 1.22 to 1.67) and mortality (statistically significant risk estimates ranging from 1.79 to 5.00) among nonpersistent individuals were also consistently reported. Conclusions Observational studies consistently report an increased risk of adverse outcomes associated with poor statin adherence. These findings have important implications for patients and physicians and emphasize the importance of monitoring and encouraging adherence to statin therapy. PMID:25364801

  5. Statin use and risk of disease recurrence and death after radical prostatectomy.

    Science.gov (United States)

    Keskiväli, Teemu; Kujala, Paula; Visakorpi, Tapio; Tammela, Teuvo L J; Murtola, Teemu J

    2016-04-01

    Statins have been linked with improved prostate cancer survival and lower risk of recurrence in men treated with radiation therapy. However, the association is unclear for surgically-treated men. We studied the risk of prostate cancer recurrence and death by statin usage after radical prostatectomy in a cohort of prostate cancer patients treated with radical prostatectomy. A cohort of 1,314 men who underwent curative-intent radical prostatectomy at the Tampere University Hospital, Tampere, Finland during 1995-2009 were linked to national prescription database to obtain detailed information on statin purchases. The risk of PSA recurrence and death (overall and prostate cancer-specific) by statin use before and after the surgery were evaluated using Cox regression with model adjustment for tumor characteristics, total cholesterol and simultaneous use of antidiabetic and antihypertensive drugs. Tissue expression of putative prognostic markers were measured from a subgroup of 323 men. During the median follow-up of 8.6 years after surgery 484 men recurred, while 244 men died (32 due to prostate cancer). In general statin use before or after prostatectomy was not associated with risk of disease recurrence or death. Tissue expression of Ki-67 and ERG modified the association between statin use and risk of disease recurrence; the risk estimates were lower in men with Ki-67 expression above the median (P for interaction 0.001 and 0.004 for statin use before and after prostatectomy, respectively) and no ERG expression in the tumor tissue (P for interaction 0.006 and 0.011). Statin use generally did not affect prostate cancer prognosis after prostatectomy. The effect on disease recurrence may depend on tumor properties, such as proliferation activity. Thus possible future prospective studies should recognize and enroll subgroups of prostate cancer patients most likely to benefit from statins. © 2015 Wiley Periodicals, Inc.

  6. National trends in statin use by coronary heart disease risk category.

    Directory of Open Access Journals (Sweden)

    Jun Ma

    2005-05-01

    Full Text Available Only limited research tracks United States trends in the use of statins recorded during outpatient visits, particularly use by patients at moderate to high cardiovascular risk.Data collected between 1992 and 2002 in two federally administered surveys provided national estimates of statin use among ambulatory patients, stratified by coronary heart disease risk based on risk factor counting and clinical diagnoses. Statin use grew from 47% of all lipid-lowering medications in 1992 to 87% in 2002, with atorvastatin being the leading medication in 2002. Statin use by patients with hyperlipidemia, as recorded by the number of patient visits, increased significantly from 9% of patient visits in 1992 to 49% in 2000 but then declined to 36% in 2002. Absolute increases in the rate of statin use were greatest for high-risk patients, from 4% of patient visits in 1992 to 19% in 2002. Use among moderate-risk patients increased from 2% of patient visits in 1992 to 14% in 1999 but showed no continued growth subsequently. In 2002, 1 y after the release of the Adult Treatment Panel III recommendations, treatment gaps in statin use were detected for more than 50% of outpatient visits by moderate- and high-risk patients with reported hyperlipidemia. Lower statin use was independently associated with younger patient age, female gender, African American race (versus non-Hispanic white, and non-cardiologist care.Despite notable improvements in the past decade, clinical practice fails to institute recommended statin therapy during many ambulatory visits of patients at moderate-to-high cardiovascular risk. Innovative approaches are needed to promote appropriate, more aggressive statin use for eligible patients.

  7. Patient beliefs and attitudes to taking statins: systematic review of qualitative studies.

    Science.gov (United States)

    Ju, Angela; Hanson, Camilla S; Banks, Emily; Korda, Rosemary; Craig, Jonathan C; Usherwood, Tim; MacDonald, Peter; Tong, Allison

    2018-06-01

    Statins are effective in preventing cardiovascular disease (CVD) events and are recommended for at-risk individuals but estimated adherence rates are low. To describe patients' perspectives, experiences, and attitudes towards taking statins. Systematic review of qualitative studies reporting perspectives of patients on statins. PsycINFO, CINAHL, Embase, MEDLINE, and PhD dissertations from inception to 6 October 2016 were searched for qualitative studies on adult patients' perspectives on statins. All text and participant quotations were extracted from each article and analysed by thematic synthesis. Thirty-two studies involving 888 participants aged 22-93 years across eight countries were included. Seven themes were identified: confidence in prevention (trust in efficacy, minimising long-term catastrophic CVD, taking control, easing anxiety about high cholesterol); routinising into daily life; questioning utility (imperceptible benefits, uncertainties about pharmacological mechanisms); medical distrust (scepticism about overprescribing, pressure to start therapy); threatening health (competing priorities and risks, debilitating side effects, toxicity to body); signifying sickness (fear of perpetual dependence, losing the battle); and financial strain. An expectation that statins could prevent CVD and being able to integrate the statin regimen in daily life facilitated acceptance of statins among patients. However, avoiding the 'sick' identity and prolonged dependence on medications, uncertainties about the pharmacological mechanisms, risks to health, side effects, costs, and scepticism about clinicians' motives for prescribing statins were barriers to uptake. Shared decision making that addresses the risks, reasons for prescribing, patient priorities, and implementing strategies to minimise lifestyle intrusion and manage side effects may improve patient satisfaction and continuation of statins. © British Journal of General Practice 2018.

  8. Algorithms to Identify Statin Intolerance in Medicare Administrative Claim Data.

    Science.gov (United States)

    Colantonio, Lisandro D; Kent, Shia T; Huang, Lei; Chen, Ligong; Monda, Keri L; Serban, Maria-Corina; Manthripragada, Angelika; Kilgore, Meredith L; Rosenson, Robert S; Muntner, Paul

    2016-10-01

    To compare characteristics of patients with possible statin intolerance identified using different claims-based algorithms versus patients with high adherence to statins. We analyzed 134,863 Medicare beneficiaries initiating statins between 2007 and 2011. Statin intolerance and discontinuation, and high adherence to statins, defined by proportion of days covered ≥80 %, were assessed during the 365 days following statin initiation. Definition 1 of statin intolerance included statin down-titration or discontinuation with ezetimibe initiation, having a claim for a rhabdomyolysis or antihyperlipidemic event followed by statin down-titration or discontinuation, or switching between ≥3 types of statins. Definition 2 included beneficiaries who met Definition 1 and those who down-titrated statin intensity. We also analyzed beneficiaries who met Definition 2 of statin intolerance or discontinued statins. The prevalence of statin intolerance was 1.0 % (n = 1320) and 5.2 % (n = 6985) using Definitions 1 and 2, respectively. Overall, 45,266 (33.6 %) beneficiaries had statin intolerance by Definition 2 or discontinued statins and 55,990 (41.5 %) beneficiaries had high adherence to statins. Compared with beneficiaries with high adherence to statins, those with statin intolerance and who had statin intolerance or discontinued statins were more likely to be female versus male, and black, Hispanic or Asian versus white. The multivariable adjusted odds ratio for statin intolerance by Definitions 1 and 2 comparing patients initiating high versus low/moderate intensity statins were 2.82 (95%CI: 2.42-3.29), and 8.58 (8.07-9.12), respectively, and for statin intolerance or statin discontinuation was 2.35 (2.25-2.45). Definitions of statin intolerance presented herein can be applied to analyses using administrative claims data.

  9. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  10. Statins as antiarrhythmics: a systematic review part I: effects on risk of atrial fibrillation.

    Science.gov (United States)

    Abuissa, Hussam; O'Keefe, James H; Bybee, Kevin A

    2009-10-01

    Recent studies have demonstrated that statins may possess antiarrhythmic properties in addition to their lipid-lowering effects. Studies which reported the association of statins with the incidence of atrial arrhythmias were identified through a systematic review of published literature. One randomized, placebo-controlled trial of 200 patients undergoing cardiac surgery showed that atorvastatin decreased the incidence of postoperative atrial fibrillation by 61%. Observational studies in patients with stable coronary disease, left ventricular dysfunction, or those undergoing cardiac or noncardiac surgery show that statin therapy is associated with an approximately 50% lower rate of atrial fibrillation. Two small randomized trials reported conflicting results: one showing that atorvastatin reduced the recurrence of AF after electrical cardioversion and the other finding that pravastatin did not. Published data suggests that statins may possess antiarrhythmic properties that reduce the propensity for atrial fibrillation. Most of this data is observational; more randomized, placebo-controlled trials are needed.

  11. Expanding the Evidence Base: Comparing Randomized Controlled Trials and Observational Studies of Statins.

    Science.gov (United States)

    Atar, Dan; Ong, Seleen; Lansberg, Peter J

    2015-01-01

    It is widely accepted that randomized controlled trials (RCTs) are the gold standard for demonstrating the efficacy of a given therapy (results under ideal conditions). Observational studies, on the other hand, can complement this by demonstrating effectiveness (results under real-world conditions). To examine the role that observational studies can play in complementing data from RCTs, we reviewed published studies for statins, a class of drugs that have been widely used to reduce the risk of cardiovascular (CV) events by lowering low-density lipoprotein cholesterol levels. RCTs have consistently demonstrated the benefits of statin treatment in terms of CV risk reduction and have demonstrated that more intensive statin therapy has incremental benefits over less intensive treatment. Observational studies of statin use in 'real-world' populations have served to augment the evidence base generated from statin RCTs in preselected populations of patients who are often at high CV risk and have led to similar safety and efficacy findings. They have also raised questions about factors affecting medication adherence, under-treatment, switching between statins, and failure to reach low-density lipoprotein cholesterol target levels, questions for which the answers could lead to improved patient care.

  12. Identification and Management of Statin-Associated Symptoms in Clinical Practice: Extension of a Clinician Survey to 12 Further Countries.

    Science.gov (United States)

    Rosenson, Robert S; Gandra, Shravanthi R; McKendrick, Jan; Dent, Ricardo; Wieffer, Heather; Cheng, Lung-I; Catapano, Alberico L; Oh, Paul; Kees Hovingh, G; Stroes, Erik S

    2017-04-01

    Statins are the first-choice pharmacological treatment for patients with hypercholesterolemia and at risk for cardiovascular disease; however, a minority of patients experience statin-associated symptoms (SAS) and are considered to have reduced statin tolerance. The objective of this study was to establish how patients with SAS are identified and managed in clinical practice in Austria, Belgium, Colombia, Croatia, the Czech Republic, Denmark, Portugal, Switzerland, Russia, Saudi Arabia, Turkey, and the United Arab Emirates. A cross-sectional survey was conducted (2015-2016) among clinicians (n = 60 per country; Croatia: n = 30) who are specialized/experienced in the treatment of hypercholesterolemia. Participants were asked about their experience of patients presenting with potential SAS and how such patients were identified and treated. Muscle-related symptoms were the most common presentation of potential SAS (average: 51%; range across countries [RAC] 17-74%); other signs/symptoms included persistent elevation in transaminases. To establish whether symptoms are due to statins, clinicians required rechallenge after discontinuation of statin treatment (average: 77%; RAC 40-90%); other requirements included trying at least one alternative statin. Clinicians reported that half of high-risk patients with confirmed SAS receive a lower-dose statin (average: 53%; RAC 43-72%), and that most receive another non-statin lipid-lowering therapy with or without a concomitant statin (average: 65%; RAC 52-83%). The specialists and GPs surveyed use stringent criteria to establish causality between statin use and signs or symptoms, and persevere with statin treatment where possible.

  13. Statin-associated muscle-related adverse effects: a case series of 354 patients.

    Science.gov (United States)

    Cham, Stephanie; Evans, Marcella A; Denenberg, Julie O; Golomb, Beatrice A

    2010-06-01

    To characterize the properties and natural history of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-associated muscle-related adverse effects (MAEs). Patient-targeted postmarketing adverse-effect surveillance approach coupling survey design with an open-ended narrative. University-affiliated health care system. Three hundred fifty-four patients (age range 34-86 yrs) who self-reported muscle-related problems associated with statin therapy. Patients with perceived statin-associated MAEs completed a survey assessing statin drugs and dosages; characteristics of the MAEs; time course of onset, resolution, or recurrence; and impact on quality of life (QOL). Cases were assessed for putative drug adverse-effect causality by using the Naranjo adverse drug reaction probability scale criteria and were evaluated for inclusion in groups for which mortality benefit with statins has been shown. Patients reported muscle pain (93%), fatigue (88%), and weakness (85%). Three hundred patients (85%) met literature criteria for probable or definite drug adverse-effect causality. Ninety-four percent of atorvastatin usages (240/255) generated MAEs versus 61% of lovastatin usages (38/62, pstatins reproduced MAEs in 100% of 39 rechallenges versus 73% (29/40) with lower potency rechallenges (pstatin initiation varied (median 14 wks); some MAEs occurred after long-term symptom-free use. Recurrence with rechallenge had a significantly shorter latency to onset (median 2 wks). The MAEs adversely affected all assessed functional and QOL domains. Most patients with probable or definite MAEs were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy. This study complements available information on the properties and natural history of statin-associated MAEs, affirming dose dependence and strong QOL impact. The data indicating a dose-dependent relationship between MAE risk and recurrence suggest

  14. Time series evaluation of an intervention to increase statin tablet splitting by general practitioners.

    Science.gov (United States)

    Polinski, Jennifer M; Schneeweiss, Sebastian; Maclure, Malcolm; Marshall, Blair; Ramsden, Samuel; Dormuth, Colin

    2011-02-01

    Tablet splitting, in which a higher-dose tablet is split to get 2 doses, reduces patients' drug costs. Statins can be split safely. General practitioners (GPs) may not direct their patients to split statins because of safety concerns or unawareness of costs. Medical chart inserts provide cost-effective education to physicians. The aim of this study was to assess whether providing GPs with statin-splitting chart inserts would increase splitting rates, and to identify predictors of splitting. In 2005 and 2006, we faxed a statin chart insert to British Columbia GPs with a request for a telephone interview. Consenting GPs were mailed 3 statin chart inserts and interviewed by phone (the intervention). In an interrupted time series, we compared monthly rates of statin-splitting prescriptions among intervention and nonintervention GPs before, during, and after the intervention. In multivariate logistic regressions accounting for patient clustering, predictors of splitting included physician and patient demographics and the specific statin prescribed. Of 5051 GPs reached, 282 (6%) agreed to the intervention. Before the intervention, GPs' splitting rate was 2.6%; after intervention, GPs' splitting rate was 7.5%. The rate for the nonintervention GPs was 4.4%. Intervention GPs were 1.68 (95% CI, 1.12-2.53) times more likely to prescribe splitting after the intervention than were nonintervention GPs. Other predictors were a patient's female sex (odds ratio [OR] = 1.26; 95% CI, 1.18-1.34), lower patient income (OR = 1.33; 95% CI, 1.18-1.34), and a lack of drug insurance (OR = 1.89; 95% CI, 1.69-2.04). An inexpensive intervention was effective in producing a sustained increase in GPs' splitting rate during 22 months of observed follow-up. Expanding statin-splitting education to all GPs might reduce prescription costs for many patients and payors. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

  15. Does Adjuvant Treatment With Ginkgo Biloba to Statins Have Additional Benefits in Patients With Dyslipidemia?

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2018-06-01

    Full Text Available Objective: Ginkgo biloba are widely used alone or in combination with other lipid-lowering agents in the treatment of dyslipidemia in China. We conducted this meta-analysis to investigate whether adjuvant treatment with ginkgo biloba leaves to statins has incremental benefits in patients with dyslipidemia.Methods: Potential studies were searched from PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, VIP, and Wanfang database up to October 2017. Only randomized controlled trials (RCTs comparing the efficacy and safety of ginkgo biloba leaves plus statins versus statins alone in patients with dyslipidemia were included.Results: Eight RCTs involving 664 patients were included. Compared with statins therapy alone, combination of statins and ginkgo biloba leaves therapy achieved greater reductions in triglycerides [mean difference (MD -0.32 mmol/L; 95% confidence interval (CI -0.43 to -0.20], total cholesterol (MD -0.61 mmol/L; 95% CI -0.90 to -0.33, or low-density lipoprotein cholesterol (LDL-C (MD -0.32 mmol/L; 95% CI -0.48 to -0.16, and a greater increment in high-density lipoprotein cholesterol (MD 0.26 mmol/L; 95% CI 0.15 to 0.37. Subgroup analyses showed that ginkgo biloba leaves plus simvastatin appeared to achieve a greater reduction in serum levels of triglycerides, total cholesterol, and LDL-C than in combination with atorvastatin therapy.Conclusion: This meta-analysis suggests that adjuvant treatment with ginkgo biloba leaves appears to improve blood lipid parameters than statins therapy alone. More well-designed RCTs are needed to investigate the benefits of the combination of statins and ginkgo biloba leaves.

  16. Metabolomic Profiling of Statin Use and Genetic Inhibition of HMG-CoA Reductase.

    Science.gov (United States)

    Würtz, Peter; Wang, Qin; Soininen, Pasi; Kangas, Antti J; Fatemifar, Ghazaleh; Tynkkynen, Tuulia; Tiainen, Mika; Perola, Markus; Tillin, Therese; Hughes, Alun D; Mäntyselkä, Pekka; Kähönen, Mika; Lehtimäki, Terho; Sattar, Naveed; Hingorani, Aroon D; Casas, Juan-Pablo; Salomaa, Veikko; Kivimäki, Mika; Järvelin, Marjo-Riitta; Davey Smith, George; Vanhala, Mauno; Lawlor, Debbie A; Raitakari, Olli T; Chaturvedi, Nish; Kettunen, Johannes; Ala-Korpela, Mika

    2016-03-15

    Statins are first-line therapy for cardiovascular disease prevention, but their systemic effects across lipoprotein subclasses, fatty acids, and circulating metabolites remain incompletely characterized. This study sought to determine the molecular effects of statin therapy on multiple metabolic pathways. Metabolic profiles based on serum nuclear magnetic resonance metabolomics were quantified at 2 time points in 4 population-based cohorts from the United Kingdom and Finland (N = 5,590; 2.5 to 23.0 years of follow-up). Concentration changes in 80 lipid and metabolite measures during follow-up were compared between 716 individuals who started statin therapy and 4,874 persistent nonusers. To further understand the pharmacological effects of statins, we used Mendelian randomization to assess associations of a genetic variant known to mimic inhibition of HMG-CoA reductase (the intended drug target) with the same lipids and metabolites for 27,914 individuals from 8 population-based cohorts. Starting statin therapy was associated with numerous lipoprotein and fatty acid changes, including substantial lowering of remnant cholesterol (80% relative to low-density lipoprotein cholesterol [LDL-C]), but only modest lowering of triglycerides (25% relative to LDL-C). Among fatty acids, omega-6 levels decreased the most (68% relative to LDL-C); other fatty acids were only modestly affected. No robust changes were observed for circulating amino acids, ketones, or glycolysis-related metabolites. The intricate metabolic changes associated with statin use closely matched the association pattern with rs12916 in the HMGCR gene (R(2) = 0.94, slope 1.00 ± 0.03). Statin use leads to extensive lipid changes beyond LDL-C and appears efficacious for lowering remnant cholesterol. Metabolomic profiling, however, suggested minimal effects on amino acids. The results exemplify how detailed metabolic characterization of genetic proxies for drug targets can inform indications, pleiotropic effects

  17. A safe procedure for connecting a continuous renal replacement therapy device into an extracorporeal membrane oxygenation circuit.

    Science.gov (United States)

    Suga, Natsumi; Matsumura, Yosuke; Abe, Ryuzo; Hattori, Noriyuki; Nakada, Taka-Aki; Oda, Shigeto

    2017-06-01

    Patients receiving extracorporeal membrane oxygenation (ECMO) often require continuous renal replacement therapy (CRRT). The intra-circuit pressure of adult ECMO usually deviates from the physiological range. We investigated the use of CRRT connected to an ECMO circuit with physiological intra-circuit pressures (0-150 mmHg, defined as the "safety range") using an in vitro experiment involving a water-filled ECMO circuit. The intra-circuit pressure pre-pump, post-pump, and post-oxygenator were measured while varying the height of the pump or ECMO flow. The bypass conduit pressure and distance from the post-oxygenator port were measured to find the "safety point", where the bypass pressure remained within the safety range. Both drainage and return limbs of the CRRT machine were connected to the safety point and the inlet and outlet pressures of the hemofilter were recorded while varying the ECMO and CRRT flow. The pre-pump pressure only remained within the safety range for heights >75 cm (ECMO flow = 4 L/min) or ECMO flow machine safely under physiological pressures in adult patients receiving ECMO.

  18. [Help me--I do not tolerate my statin].

    Science.gov (United States)

    Nater, Harald; Perger, Ludwig; Suter, Paolo M

    2015-05-06

    Statins represent the most widely prescribed drugs. Accordingly, in daily practice statin-related muscle pain and other myopathic sensations are frequently seen. In this practice review the clinical approach to statin myopathy is discussed.

  19. The association of antidepressant and statin use with death and incident cardiovascular disease varies by depression severity.

    Science.gov (United States)

    May, Heidi T; Bair, Tami L; Reiss-Brennan, Brenda; Knight, Stacey; Anderson, Jeffrey L; Horne, Benjamin D; Brunisholz, Kimberly D; Muhlestein, Joseph B

    2017-09-01

    Depression has been reported to be associated with a greater risk of death and cardiovascular disease (CVD); however, the impact of antidepressants (ADM) on CVD risk remains controversial. Statin use is known to decrease CVD risk. Whether the use of these medications together affects CVD risk has not been studied. Patients (N = 26,828) completing the patient health questionnaire (PHQ-9), ≥40 years of age, without prior CVD, and no prior ADM use were studied. Depressive severity was categorized as none-mild (PHQ-9 score ≤14, n = 21,517) and moderate-severe (PHQ-9 score ≥15, n = 5311). Cox hazard regression was used to evaluate the association of no ADM/no statin use (n = 23,104 [86.1%]), ADM/no statin use (n = 877 [3.3%]), no ADM/statin use (n = 2627 [9.8%]), and ADM/statin use (n = 220 [.8%]) with major adverse cardiovascular events (MACE: death, CAD, stroke). Patients averaged 56 ± 12 years; 61% female. There were 1182 (4.4%) 3 year MACE events. The association of ADM and statin use with MACE varied by depressive symptom severity, with statin therapy associated with a decreased risk in the none-mild group (HR = .78, p = .007) and ADM in the moderate-high group (HR = 0.58, p = 0.02). Concomitant use of ADMs and statins did not appear to provide additive benefit.

  20. Statins and transcriptional regulation: The FXR connection

    International Nuclear Information System (INIS)

    Habeos, Ioannis; Ziros, Panos G.; Psyrogiannis, Agathoklis; Vagenakis, Apostolos G.; Papavassiliou, Athanasios G.

    2005-01-01

    Farnesoid X receptor (FXR) is a nuclear receptor involved in lipoprotein as well as glucose metabolism. Statins are widely used hypolipidemic agents with many pleiotropic actions. It is known that statins affect other nuclear hormone receptors, but no reports are available on the effect of these drugs on FXR. Employing an animal model (Syrian hamsters), we hereby present evidence to demonstrate that Simvastatin, a broadly prescribed statin, decreases the expression of FXR at both the RNA and protein levels and down-regulates its DNA-binding activity. This novel property may have important implications on the mode statins influence on lipoprotein and carbohydrate homeostasis in the organism

  1. Impact of aspirin and statins on long-term survival in patients hospitalized with acute myocardial infarction complicated by heart failure

    DEFF Research Database (Denmark)

    Lewinter, Christian; Bland, John M; Crouch, Simon

    2014-01-01

    AIMS: Aspirin and statins are established therapies for acute myocardial infarction (MI), but their benefits in patients with chronic heart failure (HF) remain elusive. We investigated the impact of aspirin and statins on long-term survival in patients hospitalized with acute MI complicated by HF...

  2. Beta-blockers and statins in the context of asthma

    Directory of Open Access Journals (Sweden)

    Joanna Pawlak

    2009-12-01

    Full Text Available Asthma is a disease with a complex pathogenesis and differentiated clinical picture with airway inflammation in its background. Many cells and cell-released substances are engaged in the course of the disease. The basic treatment strategy in asthma is based on chronic administration of inhaled glucocorticosteroids (with a strong anti-inflammatory effect and beta2-adrenoreceptor agonists (bronchodilatory effect. Much attention has been recently paid to the effects of other medicines on mechanisms important in the pathogenesis of asthma, including beta-blockers and statins. Many researchers have suggested a potentially useful role of some beta-blockers in chronic asthma therapy, particularly considering their effect on the pharmacodynamics of beta receptors in the bronchi. Moreover, statins, due to their anti-inflammatory and immunomodulatory effects, can also be useful in the management of asthma.

  3. Promoting knowledge of statins in patients with low health literacy using an audio booklet

    Directory of Open Access Journals (Sweden)

    Gossey JT

    2011-08-01

    Full Text Available J Travis Gossey1, Simon N Whitney2, Michael A Crouch3, Maria L Jibaja-Weiss2, Hong Zhang4, Robert J Volk41Department of Medicine, Weill Cornell Medical College, New York, NY, USA; 2Department of Family and Community Medicine, Baylor College of Medicine, Houston, TX, USA; 3Memorial Family Medicine Residency Program, Sugar Land, TX, USA; 4Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, and Houston Center for Education and Research on Therapeutics, Houston, TX, USABackground: Statins are generally well tolerated and effective at reducing a patient’s risk of both primary and secondary cardiovascular events. Many patients who would benefit from statin therapy either do not adhere to or stop taking their statin medication within the first year. We developed an audio booklet targeted to low health literacy patients to teach them about the benefits and risks of statins to help the patients adhere to their statin therapy.Methods: Through focus groups and an iterative design, an audio booklet was developed for both English-speaking and Spanish-speaking patients. We then compared the booklet with standard of care in 132 patients from our target patient population to measure its impact on knowledge and understanding of statins.Results: The patients enjoyed the audio booklet and showed significant increases in knowledge after listening to it when compared with those who received the standard of care materials.Conclusion: The audio booklet shows promise as a tool that can be used effectively in clinical practice to teach patients about statin therapy.Keywords: patient adherence, patient education, medical decision-making, hypercholesterolemia

  4. Statins for aortic valve stenosis

    Directory of Open Access Journals (Sweden)

    Luciana Thiago

    Full Text Available ABSTRACT BACKGROUND: Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. OBJECTIVES: To evaluate the effectiveness and safety of statins in aortic valve stenosis. METHODS: Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions. Selection criteria: Randomized controlled clinical trials (RCTs comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. Data collection and analysis: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity, freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalization for any reason, overall mortality, adverse events and patient quality of life. Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. MAIN RESULTS: We included four RCTs with 2360 participants comparing statins (1185 participants with placebo (1175 participants. We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD -0.54, 95% confidence interval (CI -1.88 to 0.80; participants = 1935; studies = 2, valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2

  5. Statins for aortic valve stenosis.

    Science.gov (United States)

    Thiago, Luciana; Tsuji, Selma Rumiko; Nyong, Jonathan; Puga, Maria Eduarda Dos Santos; Góis, Aécio Flávio Teixeira de; Macedo, Cristiane Rufino; Valente, Orsine; Atallah, Álvaro Nagib

    2016-01-01

    Aortic valve stenosis is the most common type of valvular heart disease in the USA and Europe. Aortic valve stenosis is considered similar to atherosclerotic disease. Some studies have evaluated statins for aortic valve stenosis. To evaluate the effectiveness and safety of statins in aortic valve stenosis. Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS - IBECS, Web of Science and CINAHL Plus. These databases were searched from their inception to 24 November 2015. We also searched trials in registers for ongoing trials. We used no language restrictions.Selection criteria: Randomized controlled clinical trials (RCTs) comparing statins alone or in association with other systemic drugs to reduce cholesterol levels versus placebo or usual care. Data collection and analysis: Primary outcomes were severity of aortic valve stenosis (evaluated by echocardiographic criteria: mean pressure gradient, valve area and aortic jet velocity), freedom from valve replacement and death from cardiovascular cause. Secondary outcomes were hospitalization for any reason, overall mortality, adverse events and patient quality of life.Two review authors independently selected trials for inclusion, extracted data and assessed the risk of bias. The GRADE methodology was employed to assess the quality of result findings and the GRADE profiler (GRADEPRO) was used to import data from Review Manager 5.3 to create a 'Summary of findings' table. We included four RCTs with 2360 participants comparing statins (1185 participants) with placebo (1175 participants). We found low-quality evidence for our primary outcome of severity of aortic valve stenosis, evaluated by mean pressure gradient (mean difference (MD) -0.54, 95% confidence interval (CI) -1.88 to 0.80; participants = 1935; studies = 2), valve area (MD -0.07, 95% CI -0.28 to 0.14; participants = 127; studies = 2), and aortic jet velocity (MD -0.06, 95% CI -0.26 to 0

  6. Long-term effect of statins on the risk of new-onset osteoporosis: A nationwide population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Tsung-Kun Lin

    Full Text Available Several observational cohort and meta-analytical studies in humans have shown that statin users have a lower risk of fractures or greater bone mineral densities (BMD than nonusers. However, some studies including randomized clinical trials have the opposite results, particularly in Asian populations.This study investigates the impacts of statins on new-onset osteoporosis in Taiwan.In a nationwide retrospective population-based cohort study, 45,342 subjects aged between 50-90 years having received statin therapy (statin-users since January 1 2001, and observed through December 31 2013 were selected from the National Health Insurance Research Database of Taiwan. Likewise, 115,594 patients had no statin therapy (statin-non-users were included as controls in this study. Multivariable Cox proportional hazards analysis for drug exposures was employed to evaluate the association between statin treatment and new-onset of osteoporosis risk. We also used the long-rank test to evaluate the difference of probability of osteoporosis-free survival.During the 13-year follow-up period, 16,146 of all enrolled subjects (10.03% developed osteoporosis, including 3097 statin-users (6.83% and 13,049 statin-non-users (11.29%. Overall, statin therapy reduced the risk of new-onset osteoporosis by 48% (adjusted hazard ratio [HR] 0.52; 95% CI 0.50 to 0.54. A dose-response relationship between statin treatment and the risk of new-onset osteoporosis was observed. The adjusted hazard ratios for new-onset osteoporosis were 0.84 (95% CI, 0.78 to 0.90, 0.56 (95% CI, 0.52 to 0.60 and 0.23 (95% CI, 0.21 to 0.25 when cumulative defined daily doses (cDDDs ranged from 28 to 90, 91 to 365, and more than 365, respectively, relative to nonusers. Otherwise, high-potency statins (rosuvastatin and atorvastatin and moderate-potency statin (simvastatin seemed to have a potential protective effect for osteoporosis.In this population-based cohort study, we found that statin use is associated

  7. Statins and risk of poststroke hemorrhagic complications

    Science.gov (United States)

    MacIsaac, Rachael L.; Abdul-Rahim, Azmil H.; Siegerink, Bob; Bath, Philip M.; Endres, Matthias; Lees, Kennedy R.; Nolte, Christian H.

    2016-01-01

    Objective: To assess whether statin treatment before or after acute ischemic stroke (AIS) affects the risk of acute intracerebral hemorrhage (ICH), postacute ICH, and mortality within 90 days. Methods: Data were sought from the Virtual International Stroke Trials Archive, an international repository of clinical trials data. Using propensity score matching, we retrospectively compared patients with prior statin treatment and newly initiated statin within 3 days after AIS to patients without statin exposure. Outcomes of interest were acute symptomatic ICH (sICH), any acute ICH, postacute ICH, and mortality during follow-up of 3 months. Results: A total of 8,535 patients (mean age 70 years, 54% male, median baseline NIH Stroke Scale score 13) were analyzed. After propensity score matching, prior statin use was not strongly associated with sICH (adjusted odds ratio [OR] 1.33, 95% confidence interval [CI] 0.83–2.14) or any ICH (adjusted OR 1.35, 95% CI 0.92–1.98). There was no evidence of an interaction between prior statin use and thrombolysis. New initiation of statins was not associated with postacute ICH (adjusted hazard ratio [HR] 1.60, 95% CI 0.70–3.65). There was a signal towards lower 90-day mortality in patients with prior statin use (adjusted HR 0.84, 95% CI 0.70–1.00) and especially early initiation of statins (adjusted HR 0.67, 95% CI 0.46–0.97). Conclusions: Statin use prior to AIS was not associated with early hemorrhagic complications, irrespective of treatment with thrombolysis. New initiation of statin treatment early after AIS did not affect risk of postacute ICH, but might be associated with reduced mortality. PMID:27016519

  8. Process improvement for the safe delivery of multidisciplinary-executed treatments-A case in Y-90 microspheres therapy.

    Science.gov (United States)

    Cai, Bin; Altman, Michael B; Garcia-Ramirez, Jose; LaBrash, Jason; Goddu, S Murty; Mutic, Sasa; Parikh, Parag J; Olsen, Jeffrey R; Saad, Nael; Zoberi, Jacqueline E

    To develop a safe and robust workflow for yttrium-90 (Y-90) radioembolization procedures in a multidisciplinary team environment. A generalized Define-Measure-Analyze-Improve-Control (DMAIC)-based approach to process improvement was applied to a Y-90 radioembolization workflow. In the first DMAIC cycle, events with the Y-90 workflow were defined and analyzed. To improve the workflow, a web-based interactive electronic white board (EWB) system was adopted as the central communication platform and information processing hub. The EWB-based Y-90 workflow then underwent a second DMAIC cycle. Out of 245 treatments, three misses that went undetected until treatment initiation were recorded over a period of 21 months, and root-cause-analysis was performed to determine causes of each incident and opportunities for improvement. The EWB-based Y-90 process was further improved via new rules to define reliable sources of information as inputs into the planning process, as well as new check points to ensure this information was communicated correctly throughout the process flow. After implementation of the revised EWB-based Y-90 workflow, after two DMAIC-like cycles, there were zero misses out of 153 patient treatments in 1 year. The DMAIC-based approach adopted here allowed the iterative development of a robust workflow to achieve an adaptable, event-minimizing planning process despite a complex setting which requires the participation of multiple teams for Y-90 microspheres therapy. Implementation of such a workflow using the EWB or similar platform with a DMAIC-based process improvement approach could be expanded to other treatment procedures, especially those requiring multidisciplinary management. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  9. STATIN CONTAINING COMPOSITIONS FOR TREATMENT OF CANCER

    NARCIS (Netherlands)

    Schiffelers, Raymond M.; Metselaar, J.M.; Storm, Gerrit

    2008-01-01

    The present invention relates to compositions comprising statin, and especially to the use of such compositions in the treatment of cancer or in the inhibition of cancer growth. More specifically, the invention relates to a method for targeting a statin to tumor tissue.

  10. Do statins protect against upper gastrointestinal bleeding?

    DEFF Research Database (Denmark)

    Gulmez, Sinem Ezgi; Lassen, Annmarie Touborg; Aalykke, Claus

    2009-01-01

    AIMS: Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial. We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other...

  11. Pleiotropic effects of statins in stroke prevention

    Directory of Open Access Journals (Sweden)

    Yenny Yenny

    2016-02-01

    Full Text Available Cardiovascular disease is the leading cause of death and disability, and  contributes substantially to healthcare budgets. The lipid-lowering drugs, 3-hydroxy-3-methylgulutaryl-coenzyme A (HMG-CoA reductase inhibitor or statins, reducing mortality and cardiovascular morbidity in patients with established cardiovascular disease. Statins therefore have a place in the secondary prevention of cardiovascular disease. Recent experimental and clinical studies suggest that statins may exert vascular protective effect beyond cholesterol reduction. The cholesterol-independet or “pleiotropic” effects of statin include the upregulation and activation of endothelial nitric acid synthase (eNOS that can increase nitric oxide (NO production. Augmentation of NO production increases cerebral blood flow, which can lead to neuroprotection during brain ischaemia. By inhibiting mevalonate synthesis, statins prevent the formation of several isoprenoids (including farnesylpyrophosphate and geranylgeranylpyrophosphate. Inhibiting geranylgeranylation of RhoA small G proteins increases the stability of eNOS mRNA through the remodeling of endothelial actin microfilamens. Moreover, statins directly increase eNOS activity within minutes by activating the pathway involving phosphoinositide 3-kinase and protein kinase B. In the secondary prevention of stroke, the use of statins reduces the incidence of either recurrent stroke or other major vascular events and treatment should be initiated soon after the event. The use of statins does not increase hemorrhagic stroke or cancer and may also favor atherosclerotic plaque regression.

  12. Pleiotropic effects of statins in stroke prevention

    Directory of Open Access Journals (Sweden)

    Yenny

    2009-08-01

    Full Text Available Cardiovascular disease is the leading cause of death and disability, and contributes substantially to healthcare budgets. The lipid-lowering drugs, 3-hydroxy-3-methylgulutaryl-coenzyme A (HMG-CoA reductase inhibitor or statins, reducing mortality and cardiovascular morbidity in patients with established cardiovascular disease. Statins therefore have a place in the secondary prevention of cardiovascular disease. Recent experimental and clinical studies suggest that statins may exert vascular protective effect beyond cholesterol reduction. The cholesterol-independet or “pleiotropic” effects of statin include the upregulation and activation of endothelial nitric acid synthase (eNOS that can increase nitric oxide (NO production. Augmentation of NO production increases cerebral blood flow, which can lead to neuroprotection during brain ischaemia. By inhibiting mevalonate synthesis, statins prevent the formation of several isoprenoids (including farnesylpyrophosphate and geranylgeranylpyrophosphate. Inhibiting geranylgeranylation of RhoA small G proteins increases the stability of eNOS mRNA through the remodeling of endothelial actin microfilamens. Moreover, statins directly increase eNOS activity within minutes by activating the pathway involving phosphoinositide 3-kinase and protein kinase B. In the secondary prevention of stroke, the use of statins reduces the incidence of either recurrent stroke or other major vascular events and treatment should be initiated soon after the event. The use of statins does not increase hemorrhagic stroke or cancer and may also favor atherosclerotic plaque regression.

  13. Statin use and risk for ovarian cancer

    DEFF Research Database (Denmark)

    Baandrup, L; Dehlendorff, C; Friis, Søren

    2015-01-01

    BACKGROUND: Limited data suggest that statin use reduces the risk for ovarian cancer. METHODS: Using Danish nationwide registries, we identified 4103 cases of epithelial ovarian cancer during 2000-2011 and age-matched them to 58,706 risk-set sampled controls. Conditional logistic regression....... The inverse association between statin use and mucinous tumours merits further investigation....

  14. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    International Nuclear Information System (INIS)

    Katz, Matthew S.; Minsky, Bruce D.; Saltz, Leonard B.; Riedel, Elyn; Chessin, David B.; Guillem, Jose G.

    2005-01-01

    Purpose: To assess whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, might enhance the efficacy of neoadjuvant chemoradiation in rectal cancer. Methods and Materials: Between 1996 and 2001, 358 patients with clinically resectable, nonmetastatic rectal cancer underwent surgery at Memorial Sloan-Kettering Cancer Center after neoadjuvant chemoradiation for either locally advanced tumors or low-lying tumors that would require abdominoperineal resection. We excluded 9 patients for radiation therapy dose <45 Gy or if statin use was unknown, leaving 349 evaluable patients. Median radiation therapy dose was 50.4 Gy (range, 45-55.8 Gy), and 308 patients (88%) received 5-flurouracil-based chemotherapy. Medication use, comorbid illnesses, clinical stage as assessed by digital rectal examination and ultrasound, and type of chemotherapy were analyzed for associations with pathologic complete response (pCR), defined as no microscopic evidence of tumor. Fisher's exact test was used for categoric variables, Mantel-Haenszel test for ordered categoric variables, and logistic regression for multivariate analysis. Results: Thirty-three patients (9%) used a statin, with no differences in clinical stage according to digital rectal examination or ultrasound compared with the other 324 patients. At the time of surgery, 23 nonstatin patients (7%) were found to have metastatic disease, compared with 0% for statin patients. The unadjusted pCR rates with and without statin use were 30% and 17%, respectively (p = 0.10). Variables significant univariately at the p = 0.15 level were entered into a multivariate model, as were nonsteroidal anti-inflammatory drugs (NSAIDs), which were strongly associated with statin use. The odds ratio for statin use on pCR was 4.2 (95% confidence interval, 1.7-12.1; p = 0.003) after adjusting for NSAID use, clinical stage, and type of chemotherapy. Conclusion: In multivariate analysis, statin use is associated with an improved p

  15. Influence of the use of statin on the stability of erythrocyte membranes in multiple sclerosis.

    Science.gov (United States)

    de Freitas, Mariana Vaini; de Oliveira, Marcela Ramos; dos Santos, Diogo Fernandes; de Cássia Mascarenhas Netto, Rita; Fenelon, Sheila Bernardino; Penha-Silva, Nilson

    2010-02-01

    Multiple sclerosis (MS) probably occurs by oxidative, inflammatory and autoimmune mechanisms. This study investigated the influence of statin on the stability of erythrocyte membranes in MS patients. The population was composed of one group with simvastatin therapy (20 mg/day), another group without statin therapy and a healthy control group. The stability of erythrocytes was evaluated by the half-transition points, H(50) and D(50), obtained from the curves of hemolysis induced by hypotonic shock and ethanol action, respectively. Erythrocytes of MS patients were less stable against lysis by both chaotropes. This behavior may be merely a consequence of the lifestyle of MS patients or it may be intrinsically associated with the conjunct of factors responsible for the development of the disease. The use of statin by MS patients was associated with lower levels of LDL and total cholesterol, as expected, and with higher stability of erythrocytes against ethanol compared to the values of untreated MS patients.

  16. Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia

    Directory of Open Access Journals (Sweden)

    Benes LB

    2016-12-01

    Full Text Available Lane B Benes1, Nikhil S Bassi2, Michael H Davidson1 1Department of Medicine, Section of Cardiology, 2Department of Medicine, University of Chicago, Chicago, IL, USA Abstract: The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin. Keywords: omega-3 carboxylic acids, non-HDL-C, hypertriglyceridemia, residual risk, statin

  17. Effect of statins on skeletal muscle function.

    Science.gov (United States)

    Parker, Beth A; Capizzi, Jeffrey A; Grimaldi, Adam S; Clarkson, Priscilla M; Cole, Stephanie M; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S; Simpson, Kathleen; White, C Michael; Thompson, Paul D

    2013-01-01

    Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials, and the effect of statins on muscle performance has not been carefully studied. The Effect of Statins on Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase, exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo was administered for 6 months to 420 healthy, statin-naive subjects. No individual creatine kinase value exceeded 10 times normal, but average creatine kinase increased 20.8±141.1 U/L (Pmuscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 versus 10; P=0.05). Myalgic subjects on atorvastatin or placebo had decreased muscle strength in 5 of 14 and 4 of 14 variables, respectively (P=0.69). These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average creatine kinase, suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in creatine kinase should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00609063.

  18. Statins and angiogenesis: Is it about connections?

    International Nuclear Information System (INIS)

    Khaidakov, Magomed; Wang, Wenze; Khan, Junaid A.; Kang, Bum-Yong; Hermonat, Paul L.; Mehta, Jawahar L.

    2009-01-01

    Statins, inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, have been shown to induce both angiogenic and angiostatic responses. We attempted to resolve this controversy by studying the effects of two different statins, rosuvastatin and simvastatin, in two different assay systems. In the matrigel angiogenesis assay, both statins enhanced tube formation by human umbilical vein endothelial cells (HUVECs, p < 0.01 vs. control). In the ex vivo mouse aortic ring sprouting assay, both statins virtually abolished new vessel formation (p < 0.01). As a basic difference between the two models of angiogenesis is dispersed state of endothelial cells vs. compact monolayer, we analyzed influence of statins on endothelial junction proteins. RT-PCR analysis and cytoimmunostaining of HUVECs treated with simvastatin revealed increased expression of VE-cadherin (p < 0.05). The blockade of VE-cadherin with a specific antibody reversed simvastatin-induced tube formation (p < 0.002). These data suggest that statins through VE-cadherin stimulation modulate cell-cell adhesion and diminish the ability of cells to proliferate and migrate. The observations of reduced angiogenesis in the intact vessel may relate to anti-atherosclerotic and anti-cancer effects of statins, and provide a feasible explanation for conflicting data under different experimental conditions.

  19. Statins and risk of breast cancer recurrence

    Directory of Open Access Journals (Sweden)

    Sakellakis M

    2016-11-01

    Full Text Available Minas Sakellakis,1 Karolina Akinosoglou,1 Anastasia Kostaki,2 Despina Spyropoulou,1 Angelos Koutras,1 1Department of Medicine, Division of Oncology, University Hospital, Patras Medical School, Patras, 2Department of Statistics, Athens University of Economics and Business, Athens, Greece Background: The primary end point of our study was to test whether the concurrent use of a statin is related to a lower risk of recurrence and increased relapse-free survival in patients with early breast cancer. Materials and methods: We reviewed 610 female patients with stage I, II, or III breast cancer who had been surgically treated and who had subsequently received at least adjuvant chemotherapy in order to prevent recurrence. Results: Among the 610 patients with breast cancer, 83 (13.6% were receiving a statin on a chronic basis for other medical purposes. Overall, statin users displayed longer mean relapse-free survival (16.6 vs 10.2 years, P=0.028. After data had been adjusted for patient and disease characteristics, statin users maintained a lower risk of recurrence. This favorable outcome in statin users was particularly evident when we included only younger patients in the analysis (20 vs 10 years, P=0.006. Conclusion: Statins may be linked to a favorable outcome in early breast cancer patients, especially in younger age-groups. Keywords: statins, breast, cancer, adjuvant, recurrence

  20. Equity in statin use in New Zealand

    Directory of Open Access Journals (Sweden)

    Norris P

    2014-03-01

    Full Text Available INTRODUCTION: Preventive medications such as statins are used to reduce cardiovascular risk. There is some evidence to suggest that people of lower socioeconomic position are less likely to be prescribed statins. In New Zealand, Maori have higher rates of cardiovascular disease. AIM: This study aimed to investigate statin utilisation by socioeconomic position and ethnicity in a region of New Zealand. METHODS: This was a cross-sectional study in which data were collected on all prescriptions dispensed from all pharmacies in one city during 2005/6. Linkage with national datasets provided information on patients' age, gender and ethnicity. Socioeconomic position was identified using the New Zealand Index of Socioeconomic Deprivation 2006. RESULTS: Statin use increased with age until around 75 years. Below age 65 years, those in the most deprived socioeconomic areas were most likely to receive statins. In the 55-64 age group, 22.3% of the most deprived population received a statin prescription (compared with 17.5% of the mid and 18.6% of the least deprived group. At ages up to 75 years, use was higher amongst Maori than non-Maori, particularly in middle age, where Maori have a higher risk of cardiovascular disease. In the 45-54 age group, 11.6% of Maori received a statin prescription, compared with 8.7% of non-Maori. DISCUSSION: Statin use approximately matched the pattern of need, in contrast to other studies which found under-treatment of people of low socioeconomic position. A PHARMAC campaign to increase statin use may have increased use in high-risk groups in New Zealand.

  1. Statin Selection in Qatar Based on Multi-indication Pharmacotherapeutic Multi-criteria Scoring Model, and Clinician Preference.

    Science.gov (United States)

    Al-Badriyeh, Daoud; Fahey, Michael; Alabbadi, Ibrahim; Al-Khal, Abdullatif; Zaidan, Manal

    2015-12-01

    Statin selection for the largest hospital formulary in Qatar is not systematic, not comparative, and does not consider the multi-indication nature of statins. There are no reports in the literature of multi-indication-based comparative scoring models of statins or of statin selection criteria weights that are based primarily on local clinicians' preferences and experiences. This study sought to comparatively evaluate statins for first-line therapy in Qatar, and to quantify the economic impact of this. An evidence-based, multi-indication, multi-criteria pharmacotherapeutic model was developed for the scoring of statins from the perspective of the main health care provider in Qatar. The literature and an expert panel informed the selection criteria of statins. Relative weighting of selection criteria was based on the input of the relevant local clinician population. Statins were comparatively scored based on literature evidence, with those exceeding a defined scoring threshold being recommended for use. With 95% CI and 5% margin of error, the scoring model was successfully developed. Selection criteria comprised 28 subcriteria under the following main criteria: clinical efficacy, best publish evidence and experience, adverse effects, drug interaction, dosing time, and fixed dose combination availability. Outcome measures for multiple indications were related to effects on LDL cholesterol, HDL cholesterol, triglyceride, total cholesterol, and C-reactive protein. Atorvastatin, pravastatin, and rosuvastatin exceeded defined pharmacotherapeutic thresholds. Atorvastatin and pravastatin were recommended as first-line use and rosuvastatin as a nonformulary alternative. It was estimated that this would produce a 17.6% cost savings in statins expenditure. Sensitivity analyses confirmed the robustness of the evaluation's outcomes against input uncertainties. Incorporating a comparative evaluation of statins in Qatari practices based on a locally developed, transparent, multi

  2. Skin-safe photothermal therapy enabled by responsive release of acid-activated membrane-disruptive polymer from polydopamine nanoparticle upon very low laser irradiation.

    Science.gov (United States)

    Zhu, Rui; Gao, Feng; Piao, Ji-Gang; Yang, Lihua

    2017-07-25

    How to ablate tumor without damaging skin is a challenge for photothermal therapy. We, herein, report skin-safe photothermal cancer therapy provided by the responsive release of acid-activated hemolytic polymer (aHLP) from the photothermal polydopamine (PDA) nanoparticle upon irradiation at very low dosage. Upon skin-permissible irradiation (via an 850 nm laser irradiation at the power density of 0.4 W cm -2 ), the nanoparticle aHLP-PDA generates sufficient localized-heat to bring about mild hyperthermia treatment and consequently, responsively sheds off the aHLP polymer from its PDA nanocore; this leads to selective cytotoxicity to cancer cells under the acidic conditions of the extracellular microenvironment of tumor. As a result, our aHLP-PDA nanoparticle upon irradiation at a low dosage effectively inhibits tumor growth without damaging skin, as demonstrated using animal models. Effective in mitigating the otherwise inevitable skin damage in tumor photothermal therapy, the nanosystem reported herein offers an efficient pathway towards skin-safe photothermal therapy.

  3. Safety and tolerability of prolonged-release nicotinic acid in statin-treated patients

    NARCIS (Netherlands)

    Birjmohun, R. S.; Kastelein, J. J. P.; Poldermans, D.; Stroes, E. S. G.; Hostalek, U.; Assmann, G.

    2007-01-01

    Objective: To evaluate the safety and tolerability of prolonged -release nicotinic acid (Niaspan*) added to statin therapy in patients at increased cardiovascular risk. Methods: This was a 6-month, prospective, observational, multicentre, open-label evaluation of prolonged-release nicotinic acid

  4. How safe is safe?

    International Nuclear Information System (INIS)

    Hughes, C.F.; Flood, M.

    1996-01-01

    60 and 70 degree convexo-concave valve. Nine hundred and one valves were implanted in Australia. Twelve strut fractures were reported. Two other patients have been explanted and have demonstrated 'single leg separation'. This particular problem was only investigated when two patients died of a fractured valve in the same hospital on the same day. A retrospective study of all known patients in Australia has shown poor follow up, lack of knowledge and indeed lack of interest in device failure modes. Consequently, the Australian and New Zealand Heart Valve Registry was established to track all implanted valves and to notify physicians of any new information. This is perhaps the first device-specific register in Australia. The safety of individual devices is often not known by manufacturers, regulators and clinicians alike. No follow up is available and large volume long term studies are yet to be implemented for the majority of devices. Without such studies and without mandatory problem reporting, the relative safety of medical devices will continue to be measured by banner headlines, sensational TV 'grabs' and protracted law suits. At present, only schemes such as the Problem Reporting Scheme can tell us (albeit vaguely) 'how safe is safe'

  5. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    International Nuclear Information System (INIS)

    Kollmeier, Marisa A.; Katz, Matthew S.; Mak, Kimberley; Yamada, Yoshiya; Feder, David J.; Zhang Zhigang; Jia Xiaoyu; Shi Weiji; Zelefsky, Michael J.

    2011-01-01

    Purpose: To investigate the association between 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and biochemical and survival outcomes after high-dose radiotherapy (RT) for prostate cancer. Methods and Materials: A total of 1711 men with clinical stage T1-T3 prostate cancer were treated with conformal RT to a median dose of 81 Gy during 1995-2007. Preradiotherapy medication data were available for 1681 patients. Three hundred eighty-two patients (23%) were taking a statin medication at diagnosis and throughout RT. Nine hundred forty-seven patients received a short-course of neoadjuvant and concurrent androgen-deprivation therapy (ADT) with RT. The median follow-up was 5.9 years. Results: The 5- and 8-year PSA relapse-free survival (PRFS) rates for statin patients were 89% and 80%, compared with 83% and 74% for those not taking statins (p = 0.002). In a multivariate analysis, statin use (hazard ratio [HR] 0.69, p = 0.03), National Comprehensive Cancer Network (NCCN) low-risk group, and ADT use were associated with improved PRFS. Only high-risk patients in the statin group demonstrated improvement in PRFS (HR 0.52, p = 0.02). Across all groups, statin use was not associated with improved distant metastasis-free survival (DMFS) (p = 0.51). On multivariate analysis, lower NCCN risk group (p = 0.01) and ADT use (p = 0.005) predicted improved DMFS. Conclusions: Statin use during high-dose RT for clinically localized prostate cancer was associated with a significant improvement in PRFS in high-risk patients. These data suggest that statins have anticancer activity and possibly provide radiosensitization when used in conjunction with RT in the treatment of prostate cancer.

  6. Statin use and survival following glioblastoma multiforme

    DEFF Research Database (Denmark)

    Gaist, David; Hallas, Jesper; Friis, Søren

    2014-01-01

    with glioblastoma multiforme (GBM). METHODS: We identified 1562 patients diagnosed with GBM during 2000-2009 from the Danish Cancer Registry and linked this cohort to Danish nationwide demographic and health registries. Within the GBM cohort, each patient recorded as using statins prior to diagnosis (defined as ≥2......-cause death associated with prediagnostic statin use. RESULTS: A total of 339 GBM patients were included in the analyses. Of these, 325 died during median follow-up of 6.9 months (interquartile range: 3.8-13.4 months). Prediagnostic statin use was associated with a reduced HR of death (0.79; 95% CI: 0......: 0.63-1.01). CONCLUSION: Long-term prediagnostic statin use may improve survival following GBM....

  7. Statins: antimicrobial resistance breakers or makers?

    Directory of Open Access Journals (Sweden)

    Humphrey H.T. Ko

    2017-10-01

    Full Text Available Introduction The repurposing of non-antibiotic drugs as adjuvant antibiotics may help break antimicrobial resistance (AMR. Statins are commonly prescribed worldwide to lower cholesterol. They also possess qualities of AMR “breakers”, namely direct antibacterial activity, synergism with antibiotics, and ability to stimulate the host immune system. However, statins’ role as AMR breakers may be limited. Their current extensive use for cardiovascular protection might result in selective pressures for resistance, ironically causing statins to be AMR “makers” instead. This review examines statins’ potential as AMR breakers, probable AMR makers, and identifies knowledge gaps in a statin-bacteria-human-environment continuum. The most suitable statin for repurposing is identified, and a mechanism of antibacterial action is postulated based on structure-activity relationship analysis. Methods A literature search using keywords “statin” or “statins” combined with “minimum inhibitory concentration” (MIC was performed in six databases on 7th April 2017. After screening 793 abstracts, 16 relevant studies were identified. Unrelated studies on drug interactions; antifungal or antiviral properties of statins; and antibacterial properties of mevastatin, cerivastatin, antibiotics, or natural products were excluded. Studies involving only statins currently registered for human use were included. Results Against Gram-positive bacteria, simvastatin generally exerted the greatest antibacterial activity (lowest MIC compared to atorvastatin, rosuvastatin, and fluvastatin. Against Gram-negative bacteria, atorvastatin generally exhibited similar or slightly better activity compared to simvastatin, but both were more potent than rosuvastatin and fluvastatin. Discussion Statins may serve as AMR breakers by working synergistically with existing topical antibiotics, attenuating virulence factors, boosting human immunity, or aiding in wound healing. It

  8. Statin use is not associated with improved progression free survival in cetuximab treated KRAS mutant metastatic colorectal cancer patients: results from the CAIRO2 study.

    Directory of Open Access Journals (Sweden)

    Lisanne L Krens

    Full Text Available Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321 the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208 this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR for PFS for statin users was 1.12 (95% confidence interval 0.78-1.61 and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71-1.54. In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06-2.22. However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95-2.10. In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab.

  9. Muscle symptoms in statin users, associations with cytochrome P450, and membrane transporter inhibitor use: a subanalysis of the USAGE study.

    Science.gov (United States)

    Ito, Matthew K; Maki, Kevin C; Brinton, Eliot A; Cohen, Jerome D; Jacobson, Terry A

    2014-01-01

    Drug interactions have been identified as a risk factor for muscle-related side effects in statin users. The aim was to assess whether use of medications that inhibit cytochrome P450 (CYP450) isozymes, organic anion transporting polypeptide 1B1 (OATP1B1), or P-glycoprotein (P-gp) are associated with muscle-related symptoms among current and former statin users. Persons (n = 10,138) from the Understanding Statin Use in America and Gaps in Education (USAGE) internet survey were categorized about whether they ever reported new or worsening muscle pain while taking a statin (n = 2935) or ever stopped a statin because of muscle pain (n = 1516). Univariate and multivariate logistic regression models were used to assess associations between use of concomitant therapies that inhibit CYP450 isozymes, OATP1B1, P-gp, or a combination and muscle-related outcomes. In multivariate analyses, concomitant use of a CYP450 inhibitor was associated with increased odds for new or worse muscle pain (odds ratio [OR] = 1.42; P statin because of muscle pain (OR = 1.28; P = .037). Concomitant use of medication known to inhibit both OATP1B1 and P-gp was also associated with increased odds (OR = 1.80; P = .030) of ever having stopped a statin because of muscle pain. Concomitant use of medication(s) that inhibit statin metabolism was associated with increased odds of new or worse muscle pain while taking a statin and having previously stopped a statin because of muscle symptoms. These data emphasize the importance of enhancing the capabilities of clinicians and health systems for identifying and reducing statin drug interactions. Copyright © 2014 National Lipid Association. All rights reserved.

  10. Hydroxymethylglutaryl-CoA Reductase Inhibitors in Older Persons with Acute Myocardial Infarction: Evidence for an Age–Statin Interaction

    Science.gov (United States)

    Foody, JoAnne Micale; Rathore, Saif S.; Galusha, Deron; Masoudi, Frederick A.; Havranek, Edward P.; Radford, Martha J.; Krumholz, Harlan M.

    2009-01-01

    OBJECTIVES To characterize the relationship between hydroxymethylglutaryl-CoA reductase inhibitors (statins) and outcomes in older persons with acute myocardial infarction (AMI). DESIGN Observational study. SETTING Acute care hospitals in the United States from April 1998 to June 2001. PARTICIPANTS Medicare patients aged 65 and older with a principal discharge diagnosis of AMI (N = 65,020) who did and did not receive a discharge prescription for statins. MEASUREMENTS The primary outcome of interest was all-cause mortality at 3 years after discharge. RESULTS Of 23,013 patients with AMI assessed, 5,513 (24.0%) were receiving a statin at discharge. Nearly 40% of eligible patients (n =8,452) were aged 80 and older, of whom 1,310 (15.5%) were receiving a statin at discharge. In a multivariable model taking into account demographic, clinical, physician and hospital characteristics, and propensity score, discharge statin therapy was associated with significantly lower 3-year mortality (hazard ratio (HR) =0.89 (95% confidence interval (CI) =0.83–0.96)). In an analysis stratified by age, discharge statins were associated with lower mortality in patients younger than 80 (HR =0.84, 95% CI =0.76–0.92) but not in those aged 80 and older (HR =0.97, 95% CI =0.87–1.09). CONCLUSION Statin therapy is associated with lower mortality in older patients with AMI younger than 80 but not in those aged 80 and older, as a group. This finding questions whether statin efficacy data in younger patients can be broadly applied to the very old and indicates the need for further study of this group. PMID:16551308

  11. Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy.

    Science.gov (United States)

    Chung, Yoo-Ri; Park, Sung Wook; Choi, Shin-Young; Kim, Seung Woo; Moon, Ka Young; Kim, Jeong Hun; Lee, Kihwang

    2017-01-07

    To investigate the effects of dyslipidemia and statin therapy on progression of diabetic retinopathy and diabetic macular edema in patients with type 2 diabetes. The medical records of 110 patients with type 2 diabetes (70 statin users and 40 non-users) were retrospectively reviewed. The two outcome measures were progression of diabetic retinopathy by two or more steps on the early treatment diabetic retinopathy study scale and diabetic macular edema based on optical coherence tomography. Serum lipid profiles were analyzed from 6 months prior to diagnosis of diabetic macular edema. Diabetic retinopathy progressed in 23% of statin users and 18% of non-users (p = 0.506), but diabetic macular edema was present in 23% of statin users and 48% of non-users (p = 0.008). Statins reduced low-density lipoprotein cholesterol levels in patients with and without diabetic macular edema (p = 0.043 and p = 0.031, respectively). Among statin users, patients with diabetic macular edema had higher levels of triglycerides (p = 0.004) and lower levels of high-density lipoprotein cholesterol (p = 0.033) than those without diabetic macular edema. Logistic regression analysis showed that statin use significantly lowered the risk of diabetic macular edema [odds ratio (OR): 0.33, 95% confidence interval (CI) 0.12-0.91, p = 0.032]. Hypertriglyceridemia at 6 months prior to development of macular edema was significantly associated with central retinal thickness (OR: 1.52; 95% CI 1.14-2.02, p = 0.005). Lipid lowering therapy with statins protected against the development of diabetic macular edema and progression of diabetic retinopathy in patients with type 2 diabetes. Hypertriglyceridemia could be used as a surrogate marker for diabetic macular edema.

  12. Motivational effects of coronary artery calcium scores on statin adherence and weight loss.

    Science.gov (United States)

    Kalia, Nove K; Cespedes, Lucas; Youssef, George; Li, Dong; Budoff, Matthew J

    2015-05-01

    The aim of this study was to assess the effect on adherence to statin therapy and assess the effect of beneficial changes in behavior that resulted in weight loss in patients who underwent coronary artery calcium (CAC) scoring with cardiac computed tomography. Despite convincing data demonstrating the benefits of HmGCoA inhibitors for both primary and secondary prevention of coronary heart disease, they remain underused. Also, despite convincing data demonstrating the benefits of weight loss for both primary and secondary prevention of coronary heart disease, it remains difficult to motivate behavioral changes resulting in weight loss. In this study, we assess whether higher CAC scores are associated with increased compliance with statin medication and whether higher CAC scores are associated with beneficial lifestyle behaviors resulting in weight loss. We retrospectively analyzed patients that had undergone baseline CAC testing and returned for a follow-up scan. All patients had weight documented and were administered a questionnaire regarding compliance to medications. The primary endpoint was measurable weight loss between visit one and visit two and the self-reported compliance to statin use. The study population with data regarding statin compliance consisted of 2608 individuals (72% men, mean age 58±8 years) who were followed for a mean of 4.1±3.2 years after an initial CAC scan. Overall, statin compliance was lowest (27.4%) among those with CAC=0, and gradually increased with higher CAC scores (1-99, 39.2%; 100-399, 53.6%; ≥400, 58.8%; Ptool, a higher rate of adherences with statin therapy was observed in patients with higher CAC scores.

  13. Skin immunization by microneedle patch overcomes statin-induced suppression of immune responses to influenza vaccine.

    Science.gov (United States)

    Vassilieva, Elena V; Wang, Shelly; Li, Song; Prausnitz, Mark R; Compans, Richard W

    2017-12-19

    Recent studies indicated that in elderly individuals, statin therapy is associated with a reduced response to influenza vaccination. The present study was designed to determine effects on the immune response to influenza vaccination induced by statin administration in a mouse model, and investigate potential approaches to improve the outcome of vaccination on the background of statin therapy. We fed middle aged BALB/c mice a high fat "western" diet (WD) alone or supplemented with atorvastatin (AT) for 14 weeks, and control mice were fed with the regular rodent diet. Mice were immunized with a single dose of subunit A/Brisbane/59/07 (H1N1) vaccine, either systemically or with dissolving microneedle patches (MNPs). We observed that a greater age-dependent decline in the hemagglutinin inhibition titers occurred in systemically-immunized mice than in MNP- immunized mice. AT dampened the antibody response in the animals vaccinated by either route of vaccine delivery. However, the MNP-vaccinated AT-treated animals had ~20 times higher total antibody levels to the influenza vaccine than the systemically vaccinated group one month postvaccination. We propose that microneedle vaccination against influenza provides an approach to ameliorate the immunosuppressive effect of statin therapy observed with systemic immunization.

  14. Intravenous Administration Is an Effective and Safe Route for Cancer Gene Therapy Using the Bifidobacterium-Mediated Recombinant HSV-1 Thymidine Kinase and Ganciclovir

    Directory of Open Access Journals (Sweden)

    Huicong Zhou

    2016-06-01

    Full Text Available The herpes simplex virus thymidine kinase/ganciclovir (HSV TK/GCV system is one of the best studied cancer suicide gene therapy systems. Our previous study showed that caspase 3 expression was upregulated and bladder tumor growth was significantly reduced in rats treated with a combination of Bifidobacterium (BF and HSV TK/GCV (BF-rTK/GCV. However, it was raised whether the BF-mediated recombinant thymidine kinase combined with ganciclovir (BF-rTK/GCV was safe to administer via venous for cancer gene therapy. To answer this question, the antitumor effects of BF-rTK/GCV were mainly evaluated in a xenograft nude mouse model bearing MKN-45 gastric tumor cells. The immune response, including analysis of cytokine profiles, was analyzed to evaluate the safety of intramuscular and intravenous injection of BF-rTK in BALB/c mice. The results suggested that gastric tumor growth was significantly inhibited in vivo by BF-rTK/GCV. However, the BF-rTK/GCV had no effect on mouse body weight, indicating that the treatment was safe for the host. The results of cytokine profile analysis indicated that intravenous injection of a low dose of BF-rTK resulted in a weaker cytokine response than that obtained with intramuscular injection. Furthermore, immunohistochemical analysis showed that intravenous administration did not affect the expression of immune-associated TLR2 and TLR4. Finally, the BF-rTK/GCV inhibited vascular endothelial growth factor (VEGF expression in mouse model, which is helpful for inhibiting of tumor angiogenesis. That meant intravenous administration of BF-rTK/GCV was an effective and safe way for cancer gene therapy.

  15. Statins and Hip Fracture Prevention – A Population Based Cohort Study in Women

    Science.gov (United States)

    Helin-Salmivaara, Arja; Korhonen, Maarit J.; Lehenkari, Petri; Junnila, Seppo Y. T.; Neuvonen, Pertti J.; Ruokoniemi, Päivi; Huupponen, Risto

    2012-01-01

    Objective To study the association of long-term statin use and the risk of low-energy hip fractures in middle-aged and elderly women. Design A register-based cohort study. Setting Finland. Participants Women aged 45–75 years initiating statin therapy between 1996 and 2001 with adherence to statins ≥80% during the subsequent five years (n = 40 254), a respective cohort initiating hypertension drugs (n = 41 610), and women randomly selected from the population (n = 62 585). Main Outcome Measures Incidence rate of and hazard ratio (HR) for low-energy hip fracture during the follow-up extending up to 7 years after the 5-year exposure period. Results Altogether 199 low-energy hip fractures occurred during the 135 330 person-years (py) of follow-up in the statin cohort, giving an incidence rate of 1.5 hip fractures per 1000 py. In the hypertension and the population cohorts, the rates were 2.0 per 1000 py (312 fractures per 157 090 py) and 1.0 per 1000 py (212 fractures per 216 329 py), respectively. Adjusting for a propensity score and individual variables strongly predicting the outcome, good adherence to statins for five years was associated with a 29% decreased risk (HR 0.71; 95% CI 0.58–0.86) of a low-energy hip fracture in comparison with adherent use of hypertension drugs. The association was of the same magnitude when comparing the statin users with the population cohort, the HR being 0.69 (0.55–0.87). When women with poor (statins were compared to those with good adherence to hypertension drugs (≥80%) or to the population cohort, the protective effect associated with statin use attenuated with the decreasing level of adherence. Conclusions 5-year exposure to statins is associated with a reduced risk of low-energy hip fracture in women aged 50–80 years without prior hospitalizations for fractures. PMID:23144731

  16. Preemptive intravenous immunoglobulin allows safe and timely administration of antineoplastic therapies in patients with multiple myeloma and parvovirus B19 disease.

    Science.gov (United States)

    Katragadda, L; Shahid, Z; Restrepo, A; Muzaffar, J; Alapat, D; Anaissie, E

    2013-08-01

    Parvovirus B19 (B19) disease is a rare cause of anemia in cancer patients and often goes unrecognized, causing delays in anticancer therapy. A retrospective review was carried out of the records of patients with multiple myeloma who underwent melphalan-based autologous stem cell transplantation (MEL-ASCT) and developed B19 infection (January 2009-December 2011). Cases were defined by the presence of clinical and laboratory findings consistent with B19 disease in patients with repeatedly positive plasma quantitative polymerase chain reaction for parvovirus. Six patients qualified as cases; 5 presented with trilineage cytopenias (chronic in 1) and 1 with anemia later progressing to pancytopenia. Transfusion-dependent thrombocytopenia led to testing in 5 patients. Two of these patients also had manifestations of autoimmune disease. Therapy with intravenous immunoglobulin (IVIG) resulted in clinical and hematologic response in all; however, 1 patient, whose white blood cell counts and serum hemoglobin levels improved, required splenectomy for persistent thrombocytopenia. All patients required additional IVIG for recurrent B19 disease. Although viral load at diagnosis did not correlate with the severity of cytopenia, its decrease was associated with response during 17 of 20 evaluable episodes (P = 0.02). Preemptive IVIG allowed the safe administration of chemotherapy in 3 patients, including MEL-ASCT in 1. Parvovirus B19 can cause severe disease in myeloma patients including ASCT recipients. Thrombocytopenia - not anemia - was the leading presentation and may be associated with autoimmune conditions. Patients with unexplained cytopenias, particularly when prolonged, should undergo testing for circulating parvovirus. A reduction in viral load was associated with response to IVIG, although additional therapy was needed for recurrent disease. Most importantly, preemptive IVIG allowed for safe and timely administration of antineoplastic therapy in patients with ongoing B

  17. Absence of anti-HMG-CoA reductase autoantibodies in severe self-limited statin-related myopathy.

    Science.gov (United States)

    Floyd, James S; Brody, Jennifer A; Tiniakou, Eleni; Psaty, Bruce M; Mammen, Andrew

    2016-06-01

    Patients with self-limited statin-related myopathy improve spontaneously when statins are stopped. In contrast, patients with statin-associated autoimmune myopathy have autoantibodies recognizing 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and usually require immunosuppressive therapy to control their disease. On initial presentation, it can sometimes be difficult to distinguish between these 2 diseases, as both present with muscle pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this study was to determine whether patients with severe self-limited statin-related myopathy also make anti-HMGCR autoantibodies. We screened 101 subjects with severe self-limited cerivastatin-related myopathy for anti-HMGCR autoantibodies. No patient with severe self-limited cerivastatin-related myopathy had anti-HMGCR autoantibodies. Anti-HMGCR autoantibody testing can be used to help differentiate whether a patient has self-limited myopathy due to cerivastatin or autoimmune statin-associated myopathy; these findings may apply to other statins as well. Muscle Nerve 54: 142-144, 2016. © 2016 Wiley Periodicals, Inc.

  18. Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

    Science.gov (United States)

    Dunne, Jonathan A; Bailey, Marc A; Griffin, Kathryn J; Sohrabi, Soroush; Coughlin, Patrick A; Scott, D Julian A

    2014-01-01

    In the era of Abdominal Aortic Aneurysm (AAA) screening, pharmacotherapies to attenuate AAA growth are sought. HMG Co-A reductase inhibitors (statins) have pleiotropic actions independent of their lipid lowering effects and have been suggested as potential treatment for small AAAs. We systematically review the clinical evidence for this effect. Medline, EMBASE and the Cochrane Central Register of Controlled Trials (1950-2011) were searched for studies reporting data on the role of statin therapy on AAA growth rate. No language restrictions were placed on the search. References of retrieved articles and pertinent journals were hand searched. Included studies were reviewed by 2 independent observers. The search retrieved 164 papers, 100 were irrelevant based on their title, 47 were reviews and 1 was a letter. 8 studies were excluded based on review of their abstract leaving 8 for inclusion in the study. Eight observational clinical studies with a total of 4,466 patients were reviewed. Four studies demonstrated reduced AAA expansion in statin users while 4 studies failed to demonstrate this effect. The method of determining AAA growth rates varied significantly between the studies and the ability of many studies to control for misclassification bias was poor. The claim that statins attenuate AAA growth remains questionable. Further prospective studies with stringent identification and verification of statin usage and a standardised method of estimating AAA growth rates are required. Statin type and dose also merit consideration.

  19. Unexpected formation of gold nanoflowers by a green synthesis method as agents for a safe and effective photothermal therapy.

    Science.gov (United States)

    Yang, Da-Peng; Liu, Xuan; Teng, Choon Peng; Owh, Cally; Win, Khin Yin; Lin, Ming; Loh, Xian Jun; Wu, Yun-Long; Li, Zibiao; Ye, Enyi

    2017-10-26

    Star fruit (Averrhoa carambola) juice rich in vitamin C and polyphenolic antioxidants was used to synthesize branched gold nanoflowers. These biocompatible and stable gold nanoflowers show strong near-infrared absorption. They are successfully demonstrated to be highly efficient for both in vitro and in vivo photothermal therapy by using an 808 nm laser.

  20. Is it safe to use a kinetic therapy bed for care of patients with cervical spine injuries?

    Science.gov (United States)

    Prasarn, Mark L; Horodyski, MaryBeth; Behrend, Caleb; Del Rossi, Gianlucca; Dubose, Dewayne; Rechtine, Glenn R

    2015-02-01

    Bedrest is often used for temporary management, as well as definitive treatment, for many spinal injuries. Under such circumstances patients cannot remain flat for extended periods due to possible skin breakdown, blood clots, or pulmonary complications. Kinetic therapy beds are often used in the critical care setting, although this is felt to be unsafe for turning patients with spine fractures. We sought to evaluate whether a kinetic therapy bed would cause as much spinal motion at an unstable cervical injury as occurs during manual log-rolling on a standard intensive care unit bed. Unstable C5-C6 ligamentous injuries were surgically created in 15 fresh, whole cadavers. Sensors were affixed to C5 and C6 posteriorly and electromagnetic motion tracking analysis performed. In all cases a cervical collar was applied by an orthotist after creation of the injury. The amount of angular motion and linear displacement that occurred at this injured level was measured during manual log-rolling and patient turning using a kinetic therapy bed. For statistical analysis, the range of motion for angles about each axis and displacement in each direction was analyzed by multivariate analysis of variance with repeated measures. When comparing manual log-rolling and kinetic bed therapy, significantly more angular motion was created by the log-roll manoeuvre in flexion-extension (p=0.03) and lateral bending (p=0.01). There was no significant difference in axial rotation between the two methods (p=0.80). There were no significant differences demonstrated in medial-lateral and anterior-posterior translation. There was almost two times the axial displacement between manual log-rolling and the kinetic therapy bed and this reached statistical significance (p=0.05). There is less motion at an unstable cervical injury in flexion-extension, lateral bending, and axial displacement when turning a patient using a kinetic therapy bed as opposed to traditional manual log-rolling. It may be

  1. Quantifying public radiation exposure related to lutetium-177 octreotate therapy for the development of a safe outpatient treatment protocol.

    Science.gov (United States)

    Olmstead, Craig; Cruz, Kyle; Stodilka, Robert; Zabel, Pamela; Wolfson, Robert

    2015-02-01

    Radionuclide therapies, including treatment of neuroendocrine tumors with lutetium-177 (Lu-177) octreotate, often involve hospital admission to minimize radiation exposure to the public. Overnight admission due to Lu-177 octreotate therapy incurs additional cost for the hospital and is an inconvenience for the patient. This study endeavors to characterize the potential radiation risk to caregivers and the public should Lu-177 octreotate therapies be performed on an outpatient basis. Dose rate measurements of radiation emanating from 10 patients were taken 30 min, 4, and 20 h after initiation of Lu-177 octreotate therapy. Instadose radiation dose measurement monitors were also placed around the patients' rooms to assess the potential cumulative radiation exposure during the initial 30 min-4 h after treatment (simulating the hospital-based component of the outpatient model) as well as 4-20 h after treatment (simulating the discharged outpatient portion). The mean recorded dose rate at 30 min, 4, and 20 h after therapy was 20.4, 14.0, and 6.6 μSv/h, respectively. The majority of the cumulative dose readings were below the minimum recordable threshold of 0.03 mSv, with a maximum dose recorded of 0.18 mSv. Given the low dose rate and cumulative levels of radiation measured, the results support that an outpatient Lu-177 octreotate treatment protocol would not jeopardize public safety. Nevertheless, the concept of ALARA still requires that detailed radiation safety protocols be developed for Lu-177 octreotate outpatients to minimize radiation exposure to family members, caregivers, and the general public.

  2. Exploitation of Aspergillus terreus for the Production of Natural Statins

    Directory of Open Access Journals (Sweden)

    Mishal Subhan

    2016-04-01

    Full Text Available The fungus Aspergillus (A. terreus has dominated the biological production of the “blockbuster” drugs known as statins. The statins are a class of drugs that inhibit HMG-CoA reductase and lead to lower cholesterol production. The statins were initially discovered in fungi and for many years fungi were the sole source for the statins. At present, novel chemically synthesised statins are produced as inspired by the naturally occurring statin molecules. The isolation of the natural statins, compactin, mevastatin and lovastatin from A. terreus represents one of the great achievements of industrial microbiology. Here we review the discovery of statins, along with strategies that have been applied to scale up their production by A. terreus strains. The strategies encompass many of the techniques available in industrial microbiology and include the optimization of media and fermentation conditions, the improvement of strains through classical mutagenesis, induced genetic manipulation and the use of statistical design.

  3. Review Article Therapeutic Potential of Statins in Age-related ...

    African Journals Online (AJOL)

    2011-08-09

    Aug 9, 2011 ... Keywords: Age-related macular, Non-invasive treatment, Pleiotropic effects, Prevention, Statins. Received 14 June ... two types: non-exudative or “dry', characterised by .... Dam Eye Study in Wisconsin, statin use at the 10-.

  4. A survey of the FDA's AERS database regarding muscle and tendon adverse events linked to the statin drug class.

    Directory of Open Access Journals (Sweden)

    Keith B Hoffman

    Full Text Available BACKGROUND: Cholesterol management drugs known as statins are widely used and often well tolerated; however, a variety of muscle-related side effects can arise. These adverse events (AEs can have serious impact, and form a significant barrier to therapy adherence. Surveillance of post-marketing AEs is of vital importance to understand real-world AEs and reporting differences between individual statin drugs. We conducted a review of post-approval muscle and tendon AE reports in association with statin use, to assess differences within the drug class. METHODS: We analyzed all case reports from the FDA AE Reporting System (AERS database linking muscle-related AEs to statin use (07/01/2005-03/31/2011. Drugs examined were: atorvastatin, simvastatin, lovastatin, pravastatin, rosuvastatin, and fluvastatin. RESULTS: Relative risk rates for rosuvastatin were consistently higher than other statins. Atorvastatin and simvastatin showed intermediate risks, while pravastatin and lovastatin appeared to have the lowest risk rates. Relative risk of muscle-related AEs, therefore, approximately tracked with per milligram LDL-lowering potency, with fluvastatin an apparent exception. Incorporating all muscle categories, rates for atorvastatin, simvastatin, pravastatin, and lovastatin were, respectively, 55%, 26%, 17%, and 7.5% as high, as rosuvastatin, approximately tracking per milligram potency (Rosuvastatin>Atorvastatin>Simvastatin>Pravastatin ≈ Lovastatin and comporting with findings of other studies. Relative potency, therefore, appears to be a fundamental predictor of muscle-related AE risk, with fluvastatin, the least potent statin, an apparent exception (risk 74% vs rosuvastatin. INTERPRETATION: AE reporting rates differed strikingly for drugs within the statin class, with relative reporting aligning substantially with potency. The data presented in this report offer important reference points for the selection of statins for cholesterol management in

  5. Nutraceuticals in the management of patients with statin-associated muscle symptoms, with a note on real-world experience.

    Science.gov (United States)

    Ward, Natalie C; Pang, Jing; Ryan, Jacqueline D M; Watts, Gerald F

    2018-01-01

    There is considerable evidence for the role of low-density lipoprotein cholesterol (LDL-C) in the development of atherosclerotic cardiovascular disease. Although statin therapy remains the most frequency prescribed medication to reduce LDL-C and lower risk of cardiovascular disease, a considerable number of patients develop muscle-related side affects. This review summarizes recent literature supporting the role of nutraceuticals as LDL-C-lowering therapy in statin-intolerant patients, with evidence from our own clinical practices. © 2018 Wiley Periodicals, Inc.

  6. The Role of Statins in Disease Modification and Cardiovascular Risk in Rheumatoid Arthritis

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    Stergios Soulaidopoulos

    2018-02-01

    Full Text Available Rheumatoid arthritis (RA is an autoimmune, inflammatory disorder associated with excess cardiovascular morbidity and mortality. A complex interplay between traditional risk factors (dyslipidemia, insulin resistance, arterial hypertension, obesity, smoking and chronic inflammation is implicated in the development of premature atherosclerosis and consequently in the higher incidence of cardiovascular events observed in RA patients. Despite the acknowledgment of elevated cardiovascular risk among RA individuals, its management remains suboptimal. While statin administration has a crucial role in primary and secondary cardiovascular disease prevention strategies as lipid modulating factors, there are limited data concerning the precise benefit of such therapy in patients with RA. Systemic inflammation and anti-inflammatory treatments influence lipid metabolism, leading to variable states of dyslipidemia in RA. Hence, the indications for statin therapy for cardiovascular prevention may differ between RA patients and the general population and the precise role of lipid lowering treatment in RA is yet to be established. Furthermore, some evidence supports a potential beneficial impact of statins on RA disease activity, attributable to their anti-inflammatory and immunomodulatory properties. This review discusses existing data on the efficacy of statins in reducing RA-related cardiovascular risk as well as their potential beneficial effects on disease activity.

  7. Long-term Conventionally Dosed Vancomycin Therapy In Patients With Orthopaedic Implant-related Infections Seems As Effective And Safe As Long-term Penicillin Or Clindamycin Therapy. A Retrospective Cohort Study Of 103 Patients.

    Science.gov (United States)

    Aleman, Jacomien; Moojen, Dirk Jan F; van Ogtrop, Marc L; Poolman, Rudolf W; Franssen, Eric J F

    2018-01-01

    vancomycin, as initial therapy, was not significantly less effective and safe as long-term treatment with an antibiotic of the penicillin class or clindamycin, as initial therapy.

  8. Risk of Intracranial Hemorrhage From Statin Use in Asians: A Nationwide Cohort Study.

    Science.gov (United States)

    Chang, Chia-Hsuin; Lin, Chin-Hsien; Caffrey, James L; Lee, Yen-Chieh; Liu, Ying-Chun; Lin, Jou-Wei; Lai, Mei-Shu

    2015-06-09

    Reports of statin usage and increased risk of intracranial hemorrhage (ICH) have been inconsistent. This study examined potential associations between statin usage and the risk of ICH in subjects without a previous history of stroke. Patients initiating statin therapy between 2005 and 2009 without a previous history of ischemic or hemorrhagic stroke were identified from Taiwan's National Health Insurance database. Participants were stratified by advanced age (≥70 years), sex, and diagnosed hypertension. The outcome of interest was hospital admission for ICH (International Classification of Diseases, Ninth Revision, Clinical Modification codes 430, 431, 432). Cox regression models were applied to estimate the hazard ratio of ICH. The cumulative statin dosage stratified by quartile and adjusted for baseline disease risk score served as the primary variable using the lowest quartile of cumulative dosage as a reference. There were 1 096 547 statin initiators with an average follow-up of 3.3 years. The adjusted hazard ratio for ICH between the highest and the lowest quartile was nonsignificant at 1.06 with a 95% confidence interval spanning 1.00 (0.94-1.19). Similar nonsignificant results were found in sensitivity analyses using different outcome definitions or model adjustments, reinforcing the robustness of the study findings. Subgroup analysis identified an excess of ICH frequency in patients without diagnosed hypertension (adjusted hazard ratio 1.36 [1.11-1.67]). In general, no association was observed between cumulative statin use and the risk of ICH among subjects without a previous history of stroke. An increased risk was identified among the nonhypertensive cohort, but this finding should be interpreted with caution. © 2015 American Heart Association, Inc.

  9. Effect of metformin monotherapy on serum lipid profile in statin-naïve individuals with newly diagnosed type 2 diabetes mellitus: a cohort study

    Directory of Open Access Journals (Sweden)

    Szu Han Lin

    2018-04-01

    Full Text Available Background Cardiovascular disease is a major cause of mortality and morbidity in people with type 2 diabetes mellitus (T2DM. Studies have consistently identified dyslipidemia as an important risk factor for the development of macrovascular disease. The landmark United Kingdom Prospective Diabetes Study has shown that metformin therapy reduces cardiovascular events in overweight people with T2DM. This study investigates the effect of metformin monotherapy on serum lipid profile in statin-naïve individuals with newly diagnosed T2DM, and whether the effect, if any, is dosage-related. Methods This cohort study enrolled individuals exceeding 20 years of age, with recent onset T2DM, who received at least 12 months of metformin monotherapy and blood tests for serum lipid at 6-month intervals. Exclusion criteria involved people receiving any additional antidiabetic medication or lipid-lowering drug therapy. Lipid-modifying effect of metformin was recorded as levels of serum triglycerides (TG, high density lipoprotein cholesterol (HDL-C, and low density lipoprotein cholesterol (LDL-C measured at six month intervals. Results The study enrolled 155 participants with a mean age of 58.6 years and average glycosylated hemoglobin A1c of 8%. After initiating metformin therapy, LDL-C was significantly reduced from 111 mg/dl to 102 mg/dL at 6 months (P < 0.001, TG was reduced from 132 mg/dl to 122 mg/dL at 12 months (P = 0.046, and HDL-C increased from 45.1 mg/dL to 46.9 mg/dL at 12 months (P = 0.02. However, increasing the dosage of metformin yielded no significant effect on its lipid-lowering efficacy. Discussion Metformin monotherapy appreciably improves dyslipidemia in statin-naive people with T2DM. Its lipid-modifying effect may be attributable to insulin sensitization, reduction of irreversibly glycated LDL-C, and weight loss. In practice, people with dyslipidemia who are ineligible for lipid-lowering agents may benefit from metformin therapy

  10. Statin use and vitreoretinal surgery: Findings from a Finnish population-based cohort study.

    Science.gov (United States)

    Loukovaara, Sirpa; Sahanne, Sari; Takala, Annika; Haukka, Jari

    2018-01-16

    Vitreoretinal (VR) surgery is the third most common intraocular surgery after refractive and cataract surgery. The impact of statin therapy on VR surgery outcomes remains unclear, despite a potentially beneficial effect. We explored the association of preoperative statin therapy and the need for revitrectomy after primary vitrectomy. Our historical, population-based, register-based, VR surgery cohort consisted of 5709 patients operated in a tertiary, academic referral hospital in Finland, during 2008-2014, covering 6.5 years. Subgroup analysis was performed as follows: eyes operated due to (i) rhegmatogenous retinal detachment (RRD), (ii) VR interface diseases (macular pucker/hole), (iii) diabetic maculopathy or proliferative retinopathy, (iv) vitreous haemorrhage, (v) lens subluxation, (vi) vitreous opacities or (vii) other VR indication. The primary end-point event was revitrectomy during a postoperative follow-up period of 1 year due to retinal redetachment, vitreous rehaemorrhage, postoperative endophthalmitis, recurrent pucker or unclosed macular hole. Rhegmatogenous retinal detachment (RRD) was the second most frequent indication of VR surgery, including 1916 patients, with 305 re-operations with rate 0.20 (95% CI 0.18-0.23) per person-year. Statin treatment in time of operation was associated with lower risk of re-operation according to relative scale (incidence rate ratio 0.72, 95% CI 0.53-0.97), but not in absolute scale (incidence rate difference -0.58, 95% CI -4.30 to 3.15 for 100 person-years). No association with statin therapy and vitrectomy outcome was observed in the other VR subgroups. Use of statin treatment was associated with a 28% lower risk of revitrectomy in patients operated due to RRD. Further randomized clinical trials are highly warranted. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Statins and PPARα agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    International Nuclear Information System (INIS)

    Johnson, Timothy E.; Zhang, Xiaohua; Shi, Shu; Umbenhauer, Diane R.

    2005-01-01

    Statins and fibrates (weak PPARα agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPARα agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPARα compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPARγ agonist Rosiglitazone caused little or no cell death at up to 10 μM and the PPARδ ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPARα agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPARα agonism mediates in part the toxicity response to PPARα compounds. Furthermore, PPARα agonists and statins cause myotoxicity through distinct and independent pathways

  12. Statins and PPAR{alpha} agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Timothy E [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Zhang, Xiaohua [Department of Biometrics Research, Merck Research Laboratories, West Point, PA 19486 (United States); Shi, Shu [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States); Umbenhauer, Diane R [Department of Safety Assessment, Merck Research Laboratories, WP45-319, Merck Research Laboratories, West Point, PA 19486 (United States)

    2005-11-01

    Statins and fibrates (weak PPAR{alpha} agonists) are prescribed for the treatment of lipid disorders. Both drugs cause myopathy, but with a low incidence, 0.1-0.5%. However, combined statin and fibrate therapy can enhance myopathy risk. We tested the myotoxic potential of PPAR subtype selective agonists alone and in combination with statins in a differentiated rat myotube model. A pharmacologically potent experimental PPAR{alpha} agonist, Compound A, induced myotoxicity as assessed by TUNEL staining at a minimum concentration of 1 nM, while other weaker PPAR{alpha} compounds, for example, WY-14643, Gemfibrozil and Bezafibrate increased the percentage of TUNEL-positive nuclei at micromolar concentrations. In contrast, the PPAR{gamma} agonist Rosiglitazone caused little or no cell death at up to 10 {mu}M and the PPAR{delta} ligand GW-501516 exhibited comparatively less myotoxicity than that seen with Compound A. An experimental statin (Compound B) and Atorvastatin also increased the percentage of TUNEL-positive nuclei and co-treatment with WY-14643, Gemfibrozil or Bezafibrate had less than a full additive effect on statin-induced cell killing. The mechanism of PPAR{alpha} agonist-induced cell death was different from that of statins. Unlike statins, Compound A and WY-14643 did not activate caspase 3/7. In addition, mevalonate and geranylgeraniol reversed the toxicity caused by statins, but did not prevent the cell killing induced by WY-14643. Furthermore, unlike statins, Compound A did not inhibit the isoprenylation of rab4 or rap1a. Interestingly, Compound A and Compound B had differential effects on ATP levels. Taken together, these observations support the hypothesis that in rat myotube cultures, PPAR{alpha} agonism mediates in part the toxicity response to PPAR{alpha} compounds. Furthermore, PPAR{alpha} agonists and statins cause myotoxicity through distinct and independent pathways.

  13. Upsetting the apple cart: a community anticoagulation clinic survey of life event factors that undermine safe therapy.

    Science.gov (United States)

    Edmundson, Sarah; Stuenkel, Diane L; Connolly, Phyllis M

    2005-09-01

    Anticoagulation therapy is a life-enhancing therapy for patients who are at risk for embolic events secondary to atrial fibrillation, valve replacement, and other comorbidities. Clinicians are motivated to decrease the amount of time that patients are either under- or over-anticoagulated, common conditions that decrease patient safety at either extreme. The primary purpose of this descriptive study was to examine the relationship between personal life event factors as measured by Norbeck's Life Events Questionnaire, core demographics such as age and income, and anticoagulation regulation. Although many factors affect anticoagulation therapy, the precise impact of life events, positive or negative, is unknown. The salient findings of this study (n = 202) showed a small, though statistically significant, inverse relationship (r = -0.184, P < .01) between negative life events and decreased time within therapeutic international normalized ratio. Total Life Event scores showed a statistically significant inverse relationship (r = -0.159, P < .05) to international normalized ratio time within therapeutic level. Lower income was inversely associated with higher negative Life Event scores (r = -0.192, P < .01). The findings demonstrate the need for strategies that address the potential impact of life events in conjunction with coexisting screening measures used in anticoagulation clinics. Implications for this study are limited by lack of methodology documenting concurrent social support factors and limitations of the research tool to reflect life event issues specific to outpatient seniors.

  14. Statin treatment and risk of recurrent venous thromboembolism

    DEFF Research Database (Denmark)

    Nguyen, Cu Dinh; Andersson, Charlotte; Jensen, Thomas Bo

    2013-01-01

    Objectives Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin ...

  15. Stereotactic Radiation Therapy can Safely and Durably Control Sites of Extra-Central Nervous System Oligoprogressive Disease in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients Receiving Crizotinib

    Energy Technology Data Exchange (ETDEWEB)

    Gan, Gregory N., E-mail: gregory.gan@ucdenver.edu [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Weickhardt, Andrew J.; Scheier, Benjamin; Doebele, Robert C. [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States); Gaspar, Laurie E.; Kavanagh, Brian D. [Department of Radiation Oncology, University of Colorado, Aurora, Colorado (United States); Camidge, D. Ross [Department of Medical Oncology, University of Colorado, Aurora, Colorado (United States)

    2014-03-15

    Purpose: To analyze the durability and toxicity of radiotherapeutic local ablative therapy (LAT) applied to extra-central nervous system (eCNS) disease progression in anaplastic lymphoma kinase-positive non-small cell lung cancer (NSCLC) patients. Methods and Materials: Anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib and manifesting ≤4 discrete sites of eCNS progression were classified as having oligoprogressive disease (OPD). If subsequent progression met OPD criteria, additional courses of LAT were considered. Crizotinib was continued until eCNS progression was beyond OPD criteria or otherwise not suitable for further LAT. Results: Of 38 patients, 33 progressed while taking crizotinib. Of these, 14 had eCNS progression meeting OPD criteria suitable for radiotherapeutic LAT. Patients with eCNS OPD received 1-3 courses of LAT with radiation therapy. The 6- and 12-month actuarial local lesion control rates with radiation therapy were 100% and 86%, respectively. The 12-month local lesion control rate with single-fraction equivalent dose >25 Gy versus ≤25 Gy was 100% versus 60% (P=.01). No acute or late grade >2 radiation therapy-related toxicities were observed. Median overall time taking crizotinib among those treated with LAT versus those who progressed but were not suitable for LAT was 28 versus 10.1 months, respectively. Patients continuing to take crizotinib for >12 months versus ≤12 months had a 2-year overall survival rate of 72% versus 12%, respectively (P<.0001). Conclusions: Local ablative therapy safely and durably eradicated sites of individual lesion progression in anaplastic lymphoma kinase-positive NSCLC patients receiving crizotinib. A dose–response relationship for local lesion control was observed. The suppression of OPD by LAT in patients taking crizotinib allowed an extended duration of exposure to crizotinib, which was associated with longer overall survival.

  16. Statin-induced autoimmune necrotizing myositis

    Directory of Open Access Journals (Sweden)

    Katarzyna Ząber

    2016-02-01

    Full Text Available Myositides comprise a large group of disorders involving limb muscle weakness. In differential diagnosis we have to consider idiopathic myositides, myositides associated with other diseases, and those induced by external factors, e.g. drug-induced. Statins are commonly used drugs, but many patients experience a broad spectrum of adverse effects including symptoms from skeletal muscle. Physicians should pay special attention to patients reporting muscle weakness lasting longer than 12 weeks, despite statin withdrawal, as well as other symptoms: dysphagia, disturbed grip function, elevated creatinine kinase (CK levels and abnormal electromyography. The reported case deals with the problem of differential diagnosis of drug-induced muscle injury, polymyositis with a recently reported myopathy – statin-induced autoimmune necrotizing myositis, related to anti-HMGCR antibodies.

  17. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

    Directory of Open Access Journals (Sweden)

    Chase W Kessinger

    Full Text Available Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT will develop the post-thrombotic syndrome (PTS. Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice. Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1, tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs, and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.

  18. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

    Science.gov (United States)

    Kessinger, Chase W; Kim, Jin Won; Henke, Peter K; Thompson, Brian; McCarthy, Jason R; Hara, Tetsuya; Sillesen, Martin; Margey, Ronan J P; Libby, Peter; Weissleder, Ralph; Lin, Charles P; Jaffer, Farouc A

    2015-01-01

    Despite anticoagulation therapy, up to one-half of patients with deep vein thrombosis (DVT) will develop the post-thrombotic syndrome (PTS). Improving the long-term outcome of DVT patients at risk for PTS will therefore require new approaches. Here we investigate the effects of statins--lipid-lowering agents with anti-thrombotic and anti-inflammatory properties--in decreasing thrombus burden and decreasing vein wall injury, mediators of PTS, in established murine stasis and non-stasis chemical-induced venous thrombosis (N = 282 mice). Treatment of mice with daily atorvastatin or rosuvastatin significantly reduced stasis venous thrombus burden by 25% without affecting lipid levels, blood coagulation parameters, or blood cell counts. Statin-driven reductions in VT burden (thrombus mass for stasis thrombi, intravital microscopy thrombus area for non-stasis thrombi) compared similarly to the therapeutic anticoagulant effects of low molecular weight heparin. Blood from statin-treated mice showed significant reductions in platelet aggregation and clot stability. Statins additionally reduced thrombus plasminogen activator inhibitor-1 (PAI-1), tissue factor, neutrophils, myeloperoxidase, neutrophil extracellular traps (NETs), and macrophages, and these effects were most notable in the earlier timepoints after DVT formation. In addition, statins reduced DVT-induced vein wall scarring by 50% durably up to day 21 in stasis VT, as shown by polarized light microscopy of picrosirius red-stained vein wall collagen. The overall results demonstrate that statins improve VT resolution via profibrinolytic, anticoagulant, antiplatelet, and anti-vein wall scarring effects. Statins may therefore offer a new pharmacotherapeutic approach to improve DVT resolution and to reduce the post-thrombotic syndrome, particularly in subjects who are ineligible for anticoagulation therapy.

  19. Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial

    Science.gov (United States)

    Golomb, Beatrice A.; Dimsdale, Joel E.; Koslik, Hayley J.; Evans, Marcella A.; Lu, Xun; Rossi, Steven; Mills, Paul J.; Criqui, Michael H.

    2015-01-01

    Background Low/ered cholesterol is linked to aggression in some study designs. Cases/series have reported reproducible aggression increases on statins, but statins also bear mechanisms that could reduce aggression. Usual statin effects on aggression have not been characterized. Methods 1016 adults (692 men, 324 postmenopausal women) underwent double-blind sex-stratified randomization to placebo, simvastatin 20mg, or pravastatin 40mg (6 months). The Overt-Aggression-Scale-Modified–Aggression-Subscale (OASMa) assessed behavioral aggression. A significant sex-statin interaction was deemed to dictate sex-stratified analysis. Exploratory analyses assessed the influence of baseline-aggression, testosterone-change (men), sleep and age. Results The sex-statin interaction was significant (P=0.008). In men, statins tended to decrease aggression, significantly so on pravastatin: difference=-1.0(SE=0.49)P=0.038. Three marked outliers (OASMa-change ≥40 points) offset otherwise strong significance-vs-placebo: statins:-1.3(SE=0.38)P=0.0007; simvastatin:-1.4(SE=0.43)P=0.0011; pravastatin:-1.2(SE=0.45)P=0.0083. Age≤40 predicted greater aggression-decline on statins: difference=-1.4(SE=0.64)P=0.026. Aggression-protection was emphasized in those with low baseline aggression: ageaggression (N=40) statin-difference-vs-placebo=-2.4(SE=0.71)P=0.0016. Statins (especially simvastatin) lowered testosterone, and increased sleep problems. Testosterone-drop on statins predicted aggression-decline: β=0.64(SE=0.30)P=0.034, particularly on simvastatin: β=1.29(SE=0.49)P=0.009. Sleep-worsening on statins significantly predicted aggression-increase: β=2.2(SE=0.55)Paggression-increase on statins became significant with exclusion of one younger, surgically-menopausal woman (N=310) β=0.70(SE=0.34)P=0.039. The increase was significant, without exclusions, for women of more typical postmenopausal age (≥45): (N=304) β=0.68(SE=0.34)P=0.048 – retaining significance with modified age

  20. Gemfibrozil in Combination with Statins-Is It Really Contraindicated?

    Science.gov (United States)

    Wiggins, Barbara S; Saseen, Joseph J; Morris, Pamela B

    2016-04-01

    Gemfibrozil is a lipid-modifying agent that belongs to the fibric acid derivative class. Fibric acid derivatives activate peroxisome proliferator activated receptor α (PPAR-α). The primary role of these agents in clinical practice is for the management of hypertriglyceridemia. Triglycerides may be reduced by as much as 74 % in some patients. In addition to lowering triglycerides, these agents can also decrease very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) as well as raise high-density lipoprotein cholesterol (HDL-C). Based on the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults and the National Lipid Association, pharmacologic therapy to reduce triglycerides should be considered when triglyceride levels are ≥500 mg/dL. While the use of gemfibrozil has decreased over the years for a variety of reasons, muscle-associated adverse effects is the predominant reason and the one that is most clinically relevant. However, despite these concerns, there are situations in which the use of gemfibrozil in combination with a statin may be necessary. Understanding the metabolism of gemfibrozil and the degree of interaction with the various statins will assist health-care providers to optimize safety when this combination is clinically indicated.

  1. Novel strategies in glioblastoma surgery aim at safe, supra-maximum resection in conjunction with local therapies.

    Science.gov (United States)

    Wolbers, John G

    2014-01-01

    The biggest challenge in neuro-oncology is the treatment of glioblastoma, which exhibits poor prognosis and is increasing in incidence in an increasing aging population. Diverse treatment strategies aim at maximum cytoreduction and ensuring good quality of life. We discuss multimodal neuronavigation, supra-maximum tumor resection, and the postoperative treatment gap. Multimodal neuronavigation allows the integration of preoperative anatomic and functional data with intraoperative information. This approach includes functional magnetic resonance imaging (MRI) and diffusion tensor imaging in preplanning and ultrasound, computed tomography (CT), MRI and direct (sub)cortical stimulation during surgery. The practice of awake craniotomy decreases postoperative neurologic deficits, and an extensive supra-maximum resection appears to be feasible, even in eloquent areas of the brain. Intraoperative MRI- and fluorescence-guided surgery assist in achieving this goal of supra-maximum resection and have been the subject of an increasing number of reports. Photodynamic therapy and local chemotherapy are properly positioned to bridge the gap between surgery and chemoradiotherapy. The photosensitizer used in fluorescence-guided surgery persists in the remaining peripheral tumor extensions. Additionally, blinded randomized clinical trials showed firm evidence of extra cytoreduction by local chemotherapy in the tumor cavity. The cutting-edge promise is gene therapy although both the delivery and efficacy of the numerous transgenes remain under investigation. Issues such as the choice of (cell) vector, the choice of therapeutic transgene, the optimal route of administration, and biosafety need to be addressed in a systematic way. In this selective review, we present various evidence and promises to improve survival of glioblastoma patients by supra-maximum cytoreduction via local procedures while minimizing the risk of new neurologic deficit.

  2. Is there really a relationship between serum vitamin D (25OHD) levels and the musculoskeletal pain associated with statin intake? A systematic review.

    Science.gov (United States)

    Pereda, Claudia Alejandra; Nishishinya, Maria Betina

    Musculoskeletal pain associated to statin use, is the most common adverse event, leading to cessation of treatment. Several studies proposed Vitamin D deficiency to increase the risk of pain associated to statin intake. To evaluate whether vitamin D status is linked to musculoskeletal pain associated to statin use. We performed a systematic review based on electronic searches through MEDLINE, Cochrane Central and EMBASE to identify studies that 1) included patients on statin therapy 2) with vitamin D serum levels assessment, 3) in relation to musculoskeletal pain. The electronic search identified 127 potentially eligible studies, of which three were included and analysed in the present study. The heterogeneity of studies did not allow metanalysis. A systematic review and two cohort studies not included in the previous systematic review, revealed a statistically significant association of vitamin D deficit in patients with musculoskeletal pain on statin therapy. The displayed evidence suggests a significant association between 25OHD serum levels<30ng/ml and the presence of musculoskeletal pain in patients on statin therapy. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  3. SAFE Newsletter

    OpenAIRE

    2013-01-01

    The Center of Excellence SAFE – “Sustainable Architecture for Finance in Europe” – is a cooperation of the Center for Financial Studies and Goethe University Frankfurt. It is funded by the LOEWE initiative of the State of Hessen (Landes-Offensive zur Entwicklung wissenschaftlich-ökonomischer Exzellenz). SAFE brings together more than 40 professors and just as many junior researchers who are all dedicated to conducting research in support of a sustainable financial architecture. The Center has...

  4. Statin and NSAID Use and Prostate Cancer Risk

    Science.gov (United States)

    Coogan, Patricia F.; Kelly, Judith Parsells; Strom, Brian L.; Rosenberg, Lynn

    2010-01-01

    Purpose Some studies have reported reduced risks of advanced, but not early, prostate cancer among statin users, and one study found a reduced risk only among statin users who had also used nonsteroidal anti-inflammatory drugs (NSAIDs). We have previously reported no association between statin use and prostate cancer in our hospital-based Case Control Surveillance Study. The purpose of the present analyses was to update the findings by cancer stage and to evaluate the joint use of statins and NSAIDs. Methods Cases were 1367 men with prostate cancer and controls were 2007 men with diagnoses unrelated to statin or NSAID use. We used multivariable logistic regression analyses to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for statin use compared with no use, and joint use of statin and NSAIDs compared with use of neither. Results The odds ratio among regular statin users was 1.1 (95% CI 0.9–1.5), and odds ratios were similar among early and late stage cancers. The odds ratio among joint statin and NSAID users was 1.1 (95% CI 0.7–1.6). Conclusion The present results do not support a protective effect of statin use, or statin and NSAID use, on the risk of advanced prostate cancer. PMID:20582910

  5. A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.

    Science.gov (United States)

    Taylor, Beth A; Lorson, Lindsay; White, C Michael; Thompson, Paul D

    2015-02-01

    Coenzyme Q10 (CoQ10) supplementation is the most popular therapy for statin myalgia among both physicians and patients despite limited and conflicting evidence of its efficacy. This study examined the effect of coenzyme Q10 (CoQ10) supplementation on simvastatin-associated muscle pain, muscle strength and aerobic performance in patients with confirmed statin myalgia. Statin myalgia was confirmed in 120 patients with prior symptoms of statin myalgia using an 8-week randomized, double-blind crossover trial of simvastatin 20 mg/d and placebo. Forty-one subjects developed muscle pain with simvastatin but not with placebo and were randomized to simvastatin 20 mg/d combined with CoQ10 (600 mg/d ubiquinol) or placebo for 8 weeks. Muscle pain (Brief Pain Inventory [BPI]), time to pain onset, arm and leg muscle strength, and maximal oxygen uptake (VO2max) were measured before and after each treatment. Serum CoQ10 increased from 1.3 ± 0.4 to 5.2 ± 2.3 mcg/mL with simvastatin and CoQ10, but did not increase with simvastatin and placebo (1.3 ± 0.3 to 0.8 ± 0.2) (p pain severity and interference scores increased with simvastatin therapy (both p muscle strength or VO2max with simvastatin with or without CoQ10 (all p > 0.10). Marginally more subjects reported pain with CoQ10 (14 of 20 vs 7 of 18; p = 0.05). There was no difference in time to pain onset in the CoQ10 (3.0 ± 2.0 weeks) vs. placebo (2.4 ± 2.1 wks) groups (p = 0.55). A similar lack of CoQ10 effect was observed in 24 subjects who were then crossed over to the alternative treatment. Only 36% of patients complaining of statin myalgia develop symptoms during a randomized, double-blind crossover of statin vs placebo. CoQ10 supplementation does not reduce muscle pain in patients with statin myalgia. Trial RegistrationNCT01140308; www.clinicaltrials.gov. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study.

    Science.gov (United States)

    Clement, Meredith E; Park, Lawrence P; Navar, Ann Marie; Okeke, Nwora Lance; Pencina, Michael J; Douglas, Pamela S; Naggie, Susanna

    2016-08-01

    Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40-75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  7. Does the Number of Pharmacies a Patient Frequents Affect Adherence to Statins?

    Science.gov (United States)

    Christie, Russell; Sketris, Ingrid; Andreou, Pantalis; Holbrook, Anne; Levy, Adrian; Tamim, Hala

    2017-05-06

    We hypothesized that medication adherence is affected by the number of pharmacies a patient frequents. The objective was to estimate the strength of association between the number of pharmacies a patient frequents and adherence to statins. Using administrative data from the Nova Scotia Seniors' Pharmacare program, a retrospective cohort study was conducted among subjects aged 65 years and older first dispensed statin between 1998 and 2008. The Usual Provider of Care (UPC), was defined as the number of dispensation days from the most frequented pharmacy divided by the total number of dispensation days. Estimated adherence of over 80% of the Medication Possession Ratio was defined as adherent. Data were analyzed using hierarchical linear regression. The cohort of 25,641 subjects was 59% female with a mean age of 74 years. During follow-up, subjects filled prescriptions in a median of 2 (mean = 2; standard deviation = 0.88) pharmacies and visited pharmacies a median of 28 (mean = 30) times. During that time, 61% of patients used one pharmacy exclusively. Among subjects using 1 pharmacy, 59% were adherent while 58% using more than one pharmacy were adherent. However, upon adjustment for differences in distributions of age, sex, and other confounders, subjects who used more than one pharmacy had 10% decreased odds of statin adherence (odds ratio: 0.90, 95% confidence interval: 0.86-0.96). These results were robust in sensitivity analyses. Among seniors newly starting statin therapy, using a single community pharmacy was modestly associated with adherence.

  8. Statins, PCSK9 inhibitors and cholesterol homeostasis: a view from within the hepatocyte.

    Science.gov (United States)

    Sniderman, Allan D; Kiss, Robert Scott; Reid, Thomas; Thanassoulis, George; Watts, Gerald F

    2017-05-01

    Statins and PCSK9 inhibitors dramatically lower plasma LDL levels and dramatically increase LDL receptor number within hepatocyte cell membranes. It seems self-evident that total clearance of LDL particles from plasma and total delivery of cholesterol to the liver must increase in consequence. However, based on the results of stable isotope tracer studies, this analysis demonstrates the contrary to be the case. Statins do not change the production rate of LDL particles. Accordingly, at steady state, the clearance rate cannot change. Because LDL particles contain less cholesterol on statin therapy, the delivery of cholesterol to the liver must, therefore, be reduced. PCSK9 inhibitors reduce the production of LDL particles and this further reduces cholesterol delivery to the liver. With both agents, a larger fraction of a smaller pool is removed per unit time. These findings are inconsistent with the conventional model of cholesterol homeostasis within the liver, but are consistent with a new model of regulation, the multi-channel model, which postulates that different lipoprotein particles enter the hepatocyte by different routes and have different metabolic fates within the hepatocyte. The multi-channel model, but not the conventional model, may explain how statins and PCSK9 inhibitors can produce sustained increases in LDL receptor number. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  9. Use of low density lipoprotein particle number levels as an aid in statin treatment decisions for intermediate risk patients: a cost-effectiveness analysis.

    Science.gov (United States)

    Shiffman, Dov; Arellano, Andre R; Caulfield, Michael P; Louie, Judy Z; Bare, Lance A; Devlin, James J; Melander, Olle

    2016-12-07

    The 2013 ACC/AHA guideline recommended either no statin therapy or moderate-intensity statin therapy (MST) for intermediate risk patients-those with 5-7.5% 10-year risk and without cardiovascular disease (CVD), hypercholesterolemia or diabetes. The guideline further suggested that the therapy choice be based on patient-clinician discussions of risks and benefits. Since low-density lipoprotein particle (LDL-P) levels were reported to be associated with CVD independently of traditional risk factors in intermediate and low risk patients, we investigated the cost-effectiveness of using LDL-P levels to identify intermediate risk patients likely to benefit from initiating or intensifying statin therapy. We evaluated 5 care strategies for intermediate risk patients. These included the strategies suggested by the guideline: no-statin therapy and MST. We compared each of these strategies to a related strategy that incorporated LDL-P testing. No-statin therapy was compared with the strategy of MST for those with high LDL-P levels and no statin therapy for all other patients (test-and-MST). MST was compared with the strategy of high-intensity statin therapy (HST) for those with high LDL-P levels and MST for all other patients (test-and-HST). We also evaluated the strategy of HST for all. Costs (payer perspective) and utilities were assessed over a 5-year time horizon in a Markov model of 100,000 hypothetical intermediate risk patients. HST dominated all other strategies, costing less and-despite causing 739 more cases of diabetes than did MST-resulting in more quality adjusted life-years (QALYs). For patient-clinician discussions that would otherwise lead to the MST strategy, we found the test-and-HST strategy reduced costs by $4.67 MM and resulted in 134 fewer CVD events and 115 additional QALYs. For patient-clinician discussions that would otherwise lead to no statin therapy, we found that the test-and-MST strategy reduced costs by $3.25 MM, resulted in 97 fewer CVD events

  10. Hypothyroidism as a risk factor for statin intolerance.

    Science.gov (United States)

    Robison, Craig D; Bair, Tami L; Horne, Benjamin D; McCubrey, Ray O; Lappe, Donald L; Muhlestein, Joseph B; Anderson, Jeffrey L

    2014-01-01

    Three-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are one of the most commonly prescribed classes of medications because of their proven cardiovascular benefits. However, statin intolerance occurs in 5% to 20% of patients. Understanding the basis for statin intolerance remains a key issue in preventive medicine. To evaluate the association of statin intolerance with hypothyroidism in a large integrated health care system, including its sex-specific relationship and subsequent statin rechallenge and prescription history. The Intermountain Healthcare electronic medical record database identified patients (n = 2686; males = 1276, females = 1410) with a documentation of intolerance ("allergy") to at least 1 statin. Age and sex similar controls (n = 8103; males = 3892, females = 4211) were identified among patients prescribed statins without documented intolerance. Patients were evaluated for a history of hypothyroidism, development of hypothyroidism, and statin prescription history up to 5 years of follow-up. A total of 30.2% patients (210 males, 16.5%; 602 females, 42.7%) with statin intolerance had a history of hypothyroidism compared with 21.5% of statin-tolerant patients (475 males, 12.2%; 1266 females, 30.1%), for an odds ratio (OR) in the total population of 1.49 (95% confidence interval [CI] 1.34-1.65; P intolerance and hypothyroidism were less likely to be on a statin than their statin-intolerant counterparts without hypothyroidism (hazard ratio 0.84; 95% CI 0.75-0.94; P = .002). Hypothyroidism is more prevalent in those with statin intolerance, both in males and, especially, in females. People with hypothyroidism are less likely to have a prescription for a statin at follow-up than those without hypothyroidism. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  11. REAL PRACTICE OF STATINS USE AND ITS DEPENDENCE ON FOLLOW-UP IN THE SPECIALIZED MEDICAL CENTRE IN PATIENTS WITH HIGH CARDIOVASCULAR RISK (ACCORDING TO THE PROFILE REGISTER

    Directory of Open Access Journals (Sweden)

    S. Yu. Martsevich

    2015-09-01

    Full Text Available Aim. To analyze tactics of statins use in patients with high cardiovascular risk on the base of the PROFILE register data.Material and methods. Patients (n=274 who were enrolled into the PROFILE register from May, 1st till December, 31st, 2011 were divided into 3 groups: a control group (82 patients who sought medical care in the medical centre for the first time, the main group A (167 patients who were regularly followed-up in the medical centre and the main group B (25 patients who stopped follow-up in the medical centre over 2 years ago. The incidence rates of statins use and lipid target level achievement, as well as safety of statin therapy were studied in the groups.Results. 25.6, 70.7 and 52% of patients received statins in control group, main group A, and main group B, respectively. Target levels (according to the clinical guidelines of the low density cholesterol (LDC had been reached in 26.3% of patients in the main group A. This characteristic was not valid in the patients of control and main group B because of small size of these groups. Achievement of target LDC level was observed more often in use of statins in moderate and high doses, use of the original drugs, and use of rosu- vastatin. Safety of statin therapy (aspartate and alanine transaminases, creatine kinase activity, and total bilirubin was comparable in the groups of patients who reached or did not reach target LDC levels.Conclusion. High cardiovascular risk patients who were regularly followed-up in the specialized medical centre received statins therapy significantly more often. However statins use is often not correspond to the modern clinical guidelines.

  12. Which is the best lipid-modifying strategy in metabolic syndrome and diabetes: fibrates, statins or both?

    Directory of Open Access Journals (Sweden)

    Tenenbaum Alexander

    2004-12-01

    Full Text Available Abstract Although less clinical intervention studies have been performed with fibrates than with statins, there are evidences indicating that fibrates may reduce risk of cardiovascular events. The potential clinical benefit of the fenofibrate will be specified by the ongoing Fenofibrate Intervention and Event Lowering in Diabetes (FIELD study, which rationale, methods and aims have been just published. Controlled clinical trials show similar or even greater cardiovascular benefits from statins-based therapy in patient subgroups with diabetes compared with overall study populations. Therefore, statins are the drug of first choice for aggressive lipid lowering actions and reducing risk of coronary artery disease in these patients. However, current therapeutic use of statins as monotherapy is still leaving many patients with mixed atherogenic dyslipidemia at high risk for coronary events. A combination statin/fibrate therapy may be often necessary to control all lipid abnormalities in patients with metabolic syndrome and diabetes adequately, since fibrates provide additional important benefits, particularly on triglyceride and HDL-cholesterol levels. Thus, this combined therapy concentrates on all the components of the mixed dyslipidemia that often occurs in persons with diabetes or metabolic syndrome, and may be expected to reduce cardiovascular morbidity and mortality. Safety concerns about some fibrates such as gemfibrozil may lead to exaggerate precautions regarding fibrate administration and therefore diminish the use of the seagents. However, other fibrates, such as bezafibrate and fenofibrate appear to be safer and better tolerated. We believe that a proper co-administration of statins and fibrates, selected on basis of their safety, could be more effective in achieving a comprehensive lipid control as compared with monotherapy.

  13. Endothelium Protective Function of Statins in Men and Women with Coronary Atherosclerosis

    OpenAIRE

    M. V. Klimushina; N. G. Gumanova; A. Ju. Gorshkov; N. E. Gavrilova; V. A. Metel'skaja; S. A. Boytsov

    2016-01-01

    Aim. To study the relationship between serum endothelin levels and lipid-lowering therapy in patients with confirmed coronary atherosclerosis.Material and methods. Patients (n=447; 320 men and 127 women; mean age 62.7±8.8 years) with coronary atherosclerosis, confirmed by coronary angiography, were included into the study. Serum endothelin levels were assessed by enzyme immunoassay (ELISA).Results. Negative correlation between the statins receiving and serum endothelin level was found in men ...

  14. Effect of Statin Intensity on the Risk of Epilepsy After Ischaemic Stroke: Real-World Evidence from Population-Based Health Claims.

    Science.gov (United States)

    Lin, Fang-Ju; Lin, Hung-Wei; Ho, Yunn-Fang

    2018-04-01

    Statins possess neuroprotective effects. However, real-world evidence supporting their utility in post-stroke epilepsy (PSE) prevention is limited. The association between statin use, including timing of prescribing (pre-stroke vs post-stroke), type (lipophilicity, intensity of therapy) and dose intensity, and risk of developing PSE were investigated by studying Taiwanese health claims (2003-2013). Patients with new-onset ischaemic stroke were identified. The main outcome was a diagnosis of epilepsy after ischaemic stroke. According to pre-stroke statin use, groups of current users, former users, and non-users were compared using ANOVA. An extended Cox regression model was utilized to estimate the hazard ratio (HR) of PSE, with post-stroke statin use and certain comedications as time-dependent variables. Serial sensitivity analyses were performed to ensure study robustness. Of the 20,858 ischaemic stroke patients, 954 (4.6%) developed PSE. Post-stroke statin use (adjusted HR (aHR) 0.55; 95% confidence interval 0.46-0.67, p < 0.001), but not pre-stroke statin use was associated with a significantly reduced risk of developing PSE. A dose-response correlation was also observed between PSE risk reduction and quartiles of the statin cumulative defined daily dose (cDDD) (aHR 0.84, 0.67, 0.53, and 0.50 for the lowest, second, third, and highest quartiles of cDDD, respectively). Risk predictors and protectors against PSE were also characterized. The post-stroke use of statins after ischaemic stroke was associated with PSE risk reduction in a cDDD-dependent manner. Further clinical studies on the potential applications of statins for PSE prophylaxis, particularly among at-risk patients, are warranted.

  15. Evaluation of the acceptability and usability of a decision support system to encourage safe and effective use of opioid therapy for chronic, noncancer pain by primary care providers.

    Science.gov (United States)

    Trafton, Jodie; Martins, Susana; Michel, Martha; Lewis, Eleanor; Wang, Dan; Combs, Ann; Scates, Naquell; Tu, Samson; Goldstein, Mary K

    2010-04-01

    To develop and evaluate a clinical decision support system (CDSS) named Assessment and Treatment in Healthcare: Evidenced-Based Automation (ATHENA)-Opioid Therapy, which encourages safe and effective use of opioid therapy for chronic, noncancer pain. CDSS development and iterative evaluation using the analysis, design, development, implementation, and evaluation process including simulation-based and in-clinic assessments of usability for providers followed by targeted system revisions. Volunteers provided detailed feedback to guide improvements in the graphical user interface, and content and design changes to increase clinical usefulness, understandability, clinical workflow fit, and ease of completing guideline recommended practices. Revisions based on feedback increased CDSS usability ratings over time. Practice concerns outside the scope of the CDSS were also identified. Usability testing optimized the CDSS to better address barriers such as lack of provider education, confusion in dosing calculations and titration schedules, access to relevant patient information, provider discontinuity, documentation, and access to validated assessment tools. It also highlighted barriers to good clinical practice that are difficult to address with CDSS technology in its current conceptualization. For example, clinicians indicated that constraints on time and competing priorities in primary care, discomfort in patient-provider communications, and lack of evidence to guide opioid prescribing decisions impeded their ability to provide effective, guideline-adherent pain management. Iterative testing was essential for designing a highly usable and acceptable CDSS; however, identified barriers may limit the impact of the ATHENA-Opioid Therapy system and other CDSS on clinical practices and outcomes unless CDSS are paired with parallel initiatives to address these issues.

  16. COMPARATIVE EFFICACY OF THE STATINS IN PREVENTING AND TREATING OF THE CORONARY HEART DISEASE

    Directory of Open Access Journals (Sweden)

    S. V. Shalaev

    2010-01-01

    Full Text Available The possibility to stabilize and reverse the atherosclerotic plaques in coronary arteries due to therapy with atorvastatin and rosuvastatin was demonstrated in recent studies. The advantage of aggressive lipid-lowering therapy compared with standard therapy is proven in patients with both stable and acute forms of ischemic heart disease (IHD. Pleiotropic effects, in particular, effect on endothelial function, ability to reduce the blood level of C-reactive protein are important in the statins mode of action. Risk reduction of cardiovascular complications and slow down of atherosclerosis progression in patients with IHD was significantly associated with decrease in levels of both atherogenic lipids and C-reactive protein.

  17. A network meta-analysis on randomized trials focusing on the preventive effect of statins on contrast-induced nephropathy

    DEFF Research Database (Denmark)

    Peruzzi, Mariangela; De Luca, Leonardo; Thomsen, Henrik S

    2014-01-01

    -analysis. Randomized trials focusing on statins were searched and pooled with random-effect odds ratios. A total of 14 trials (6,160 patients) were included, focusing on atorvastatin (high/low dose), rosuvastatin (high dose), simvastatin (high/low dose), and placebo or no statin therapy before contrast administration....... The risk of contrast-induced nephropathy was reduced by atorvastatin high dose and rosuvastatin high dose, with no difference between these two agents. Results for atorvastatin low dose and simvastatin (high/low dose) in comparison to placebo were inconclusive. Atorvastatin and rosuvastatin administered...

  18. Role of Statin Drugs for Polycystic Ovary Syndrome.

    Science.gov (United States)

    Cassidy-Vu, Lisa; Joe, Edwina; Kirk, Julienne K

    2016-12-01

    Objective: To review the potential role and specific impact of statin drugs in women with PCOS. The evidence for this use of statins in PCOS is limited and still under further investigation. Materials and methods: A search was conducted using PubMed, DynaMed and PubMedHealth databases through October 16, 2016 using the terms polycystic ovary syndrome, PCOS, hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA, statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin . English-language trials evaluating statins in PCOS were obtained and incorporated if they provided relevant data for providers. Results: We summarize twelve trials involving statins in PCOS. The trials were predominantly 12 weeks to 3 months in length (8 of the 12 trials) and low to moderate dose of statin drugs were used. The majority (10 of 12) of the trials show that statins reduce testosterone levels or other androgen hormones (DHEA-S and androstenedione), half of the trials evaluating LH/FSH ratio show an improvement, and all had positive effects on lipid profiles. Conclusion: Statins show promising improvements in serum levels of androgens and LH/FSH ratios translating to improved cardiovascular risk factors above and beyond simply lowering LDL levels. More investigation is needed to determine if statins can clinically impact women with PCOS long term, particularly those who are young and are not yet candidates for traditional preventative treatment with a statin medication.

  19. Role of Statin Drugs for Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Lisa Cassidy Vu

    2017-03-01

    Full Text Available Objective: To review the potential role and specific impact of statin drugs in women with PCOS. The evidence for this use of statins in PCOS is limited and still under further investigation.Materials and methods: A search was conducted using PubMed, DynaMed and PubMedHealth databases through October 16, 2016 using the terms polycystic ovary syndrome, PCOS, hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA , statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. English-language trials evaluating statins in PCOS were obtained and incorporated if they provided relevant data for providers.Results: We summarize twelve trials involving statins in PCOS. The trials were predominantly 12 weeks to 3 months in length (8 of the 12 trials and low to moderate dose of statin drugs were used. The majority (10 of 12 of the trials show that statins reduce testosterone levels or other androgen hormones (DHEA-S and androstenedione, half of the trials evaluating LH/FSH ratio show an improvement, and all had positive effects on lipid profiles.Conclusion: Statins show promising improvements in serum levels of androgens and LH/FSH ratios translating to improved cardiovascular risk factors above and beyond simply lowering LDL levels. More investigation is needed to determine if statins can clinically impact women with PCOS long term, particularly those who are young and are not yet candidates for traditional preventative treatment with a statin medication. 

  20. Misperception among physicians and patients regarding the risks and benefits of statin treatment: the potential role of direct-to-consumer advertising.

    Science.gov (United States)

    Kon, Rachel H; Russo, Mark W; Ory, Bridget; Mendys, Phil; Simpson, Ross J

    2008-02-01

    Statins are commonly used to reduce the risk of heart attacks and strokes. Despite the benefit and limited risks in properly identified patients, clinicians are often challenged by patient acceptance and adherence to these medications. To assess if patients and physicians may have unfounded safety concerns about hepatotoxicity from these medications, we surveyed physicians and patients. We found inconsistent liver function-monitoring practices as well as exaggerated fears of statin-induced hepatotoxicity. Patients who received risk information from their physician were more likely to accurately estimate hepatotoxic risk than patients receiving such information from other sources. We believe these misperceptions about the relative risk and benefits of statin therapy are propagated by direct-to-consumer advertising, which may emphasize potential adverse events relative to treatment benefits. These perceptions are likely to adversely affect statin adherence, and may be addressed by patient education.

  1. Safe Haven.

    Science.gov (United States)

    Bush, Gail

    2003-01-01

    Discusses school libraries as safe havens for teenagers and considers elements that foster that atmosphere, including the physical environment, lack of judgments, familiarity, leisure, and a welcoming nature. Focuses on the importance of relationships, and taking the time to listen to teens and encourage them. (LRW)

  2. Statins, fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, omega-3 fatty acids: which drugs for which patients?

    Science.gov (United States)

    Drexel, Heinz

    2009-12-01

    Classes of lipid lowering drugs differ strongly with respect to the types of lipids or lipoproteins they predominantly affect. Statins inhibit the de-novo synthesis of cholesterol. Consequently, the liver produces less VLDL, and the serum concentration primarily of LDL cholesterol (but, to a lesser extent, also of triglycerides) is lowered. Further, statins somewhat increase HDL cholesterol. There is abundant evidence that statins lower the rate of cardiovascular events. Cardiovascular risk reduction is the better, the lower the LDL cholesterol values achieved with statin therapy are. Some evidence is available that anion exchange resins which also decrease LDL cholesterol decrease vascular risk, too. This is not the case for the ezetimibe, which strongly lowers LDL cholesterol: its potential to decrease vascular risk remains to be proven. In contrast evidence for cardiovascular risk reduction through the mainly triglyceride lowering fibrates as well as for niacin is available. Niacin is the most potent HDL increasing drug currently available and besides increasing HDL cholesterol efficaciously lowers triglycerides and LDL cholesterol. Large ongoing trials address the decisive question whether treatment with fibrates and niacin provides additional cardiovascular risk reduction when given in addition to statin treatment.

  3. Long-term compliance with beta-blockers, angiotensin-converting enzyme inhibitors, and statins after acute myocardial infarction

    DEFF Research Database (Denmark)

    Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Z

    2006-01-01

    AIMS: To study initiation, dosages, and compliance with beta-blockers, angiotensin-converting enzyme (ACE)-inhibitors, and statins in patients after acute myocardial infarction (AMI) and to identify likely targets for improvement. METHODS AND RESULTS: Patients admitted with first AMI between 1995...... and 2002 were identified by linking nationwide administrative registers. A total of 55 315 patients survived 30 days after discharge and were included; 58.3% received beta-blockers, 29.1% ACE-inhibitors, and 33.5% statins. After 1, 3, and 5 years, 78, 64, and 58% of survivors who had started therapy were...... still receiving beta-blockers, 86, 78, and 74% were receiving ACE-inhibitors, and 85, 80, and 82% were receiving statins, respectively. Increased age and female sex were associated with improved compliance. The dosages prescribed were generally 50% or less of the dosages used in clinical trials...

  4. ACC/AHA guidelines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans

    DEFF Research Database (Denmark)

    Mortensen, Martin Bødtker; Nordestgaard, Børge G; Afzal, Shoaib

    2017-01-01

    Aim We compared the 2013 American College of Cardiology/American Heart Association (ACC/AHA) and the 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines on prevention of atherosclerotic cardiovascular disease (ASCVD) using different risk prediction models [US......-calibrated around decision thresholds for statin therapy. For a Class I recommendation, 42% of individuals qualified for statins using the ACC/AHA guidelines vs. 6% with the ESC/EAS guidelines. Using ACC/AHA- vs. ESC/EAS-defined statin eligibility led to a substantial gain in sensitivity (+62% for any ASCVD and+76......% for fatal ASCVD) with a smaller loss in specificity (-35% for any ASCVD and -36% for fatal ASCVD). Similar differences between the ACC/AHA and ESC/EAS guidelines were found for men and women separately, and for Class IIa recommendations. The sensitivity and specificity of a US-PCE risk of 5% were similar...

  5. The role of acid-base imbalance in statin-induced myotoxicity.

    Science.gov (United States)

    Taha, Dhiaa A; De Moor, Cornelia H; Barrett, David A; Lee, Jong Bong; Gandhi, Raj D; Hoo, Chee Wei; Gershkovich, Pavel

    2016-08-01

    Disturbances in acid-base balance, such as acidosis and alkalosis, have potential to alter the pharmacologic and toxicologic outcomes of statin therapy. Statins are commonly prescribed for elderly patients who have multiple comorbidities such as diabetes mellitus, cardiovascular, and renal diseases. These patients are at risk of developing acid-base imbalance. In the present study, the effect of disturbances in acid-base balance on the interconversion of simvastatin and pravastatin between lactone and hydroxy acid forms have been investigated in physiological buffers, human plasma, and cell culture medium over pH ranging from 6.8-7.8. The effects of such interconversion on cellular uptake and myotoxicity of statins were assessed in vitro using C2C12 skeletal muscle cells under conditions relevant to acidosis, alkalosis, and physiological pH. Results indicate that the conversion of the lactone forms of simvastatin and pravastatin to the corresponding hydroxy acid is strongly pH dependent. At physiological and alkaline pH, substantial proportions of simvastatin lactone (SVL; ∼87% and 99%, respectively) and pravastatin lactone (PVL; ∼98% and 99%, respectively) were converted to the active hydroxy acid forms after 24 hours of incubation at 37°C. At acidic pH, conversion occurs to a lower extent, resulting in greater proportion of statin remaining in the more lipophilic lactone form. However, pH alteration did not influence the conversion of the hydroxy acid forms of simvastatin and pravastatin to the corresponding lactones. Furthermore, acidosis has been shown to hinder the metabolism of the lactone form of statins by inhibiting hepatic microsomal enzyme activities. Lipophilic SVL was found to be more cytotoxic to undifferentiated and differentiated skeletal muscle cells compared with more hydrophilic simvastatin hydroxy acid, PVL, and pravastatin hydroxy acid. Enhanced cytotoxicity of statins was observed under acidic conditions and is attributed to increased

  6. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction.

    Science.gov (United States)

    Reis, Patricia A; Alexandre, Pedro C B; D'Avila, Joana C; Siqueira, Luciana D; Antunes, Barbara; Estato, Vanessa; Tibiriça, Eduardo V; Verdonk, Franck; Sharshar, Tarek; Chrétien, Fabrice; Castro-Faria-Neto, Hugo C; Bozza, Fernando A

    2017-02-01

    Acute brain dysfunction is a frequent condition in sepsis patients and is associated with increased mortality and long-term neurocognitive consequences. Impaired memory and executive function are common findings in sepsis survivors. Although neuroinflammation and blood-brain barrier dysfunction have been associated with acute brain dysfunction and its consequences, no specific treatments are available that prevent cognitive impairment after sepsis. Experimental sepsis was induced in Swiss Webster mice by intraperitoneal injection of cecal material (5mg/kg, 500μL). Control groups (n=5/group each experiment) received 500μL of saline. Support therapy recover (saline 0.9%, 1mL and imipenem 30mg/kg) were applied (6, 24 and 48h post injection, n=5-10/group, each experiment), together or not with additive orally treatment with statins (atorvastatin/simvastatin 20mg/kg b.w.). Survival rate was monitored at 6, 24 and 48h. In a setting of experiments, animals were euthanized at 6 and 24h after induction for biochemical, immunohistochemistry and intravital analysis. Statins did not prevented mortality in septic mice, however survivors presented lower clinical score. At another setting of experiments, after 15days, mice survivors from fecal supernatant peritoneal sepsis presented cognitive dysfunction for contextual hippocampal and aversive amygdala-dependent memories, which was prevented by atorvastatin/simvastatin treatment. Systemic and brain tissue levels of proinflammatory cytokines/chemokines and activation of microglial were lower in septic mice treated with statins. Brain lipid peroxidation and myeloperoxidase levels were also reduced by statins treatment. Intravital examination of the brain vessels of septic animals revealed decreased functional capillary density and increased rolling and adhesion of leukocytes, and blood flow impairment, which were reversed by treatment with statins. In addition, treatment with statins restored the cholinergic vasodilator response

  7. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

    Science.gov (United States)

    Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

    2017-06-01

    Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p statin-monotherapy groups without any noteworthy event in both studies. These results strongly support the favourable benefit-to-risk ratio of K-877 add-on therapy in combination with statin treatment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  8. Imputation of Baseline LDL Cholesterol Concentration in Patients with Familial Hypercholesterolemia on Statins or Ezetimibe.

    Science.gov (United States)

    Ruel, Isabelle; Aljenedil, Sumayah; Sadri, Iman; de Varennes, Émilie; Hegele, Robert A; Couture, Patrick; Bergeron, Jean; Wanneh, Eric; Baass, Alexis; Dufour, Robert; Gaudet, Daniel; Brisson, Diane; Brunham, Liam R; Francis, Gordon A; Cermakova, Lubomira; Brophy, James M; Ryomoto, Arnold; Mancini, G B John; Genest, Jacques

    2018-02-01

    Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR , PCSK9 , or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy. To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions. After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] ( P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe. We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis. © 2017 American Association for Clinical Chemistry.

  9. Clinical characteristics and usage of statins in patients with stable ischemic heart disease referred for angiography or coronary artery bypass grafting

    Directory of Open Access Journals (Sweden)

    I.V. Shklianka

    2017-12-01

    Full Text Available The aim – to compare the clinical characteristics and frequency of statins usage in real clinical practice in patients referred to a specialized clinic for angiography or coronary artery bypass grafting. Materials and methods. In a retrospective slice single-center study data from a primary examination of 155 patients with stable ischemic heart disease, consecutively selected for coronary artery bypass grafting surgery, were analyzed. Depending on the inclusion of statins in the list of medicinal prescriptions, patients were retrospectively divided into two groups: those who had been prescribed statins while they were initially referred to a specialized cardiac surgery center for angiography or revascularization (n = 84 and those who were not prescribed statins (n ​​= 71. Results. The studied patients’ cohort was characterized by earlier coronary events, signs of the peripheral artery atherosclerosis and other absolute indications for treatment with statins in vast majority of cases. At the same time, groups of patients who had been and had not been prescribed statins, did not differ by vast majority of demographic, clinical and instrumental characteristics, concomitant diseases and risk factors. No statin therapy was associated with higher levels of total cholesterol and interleukin-6 compared with the group of patients taking statins (total cholesterol, respectively, 4.8 versus 4.2 mmol/l (p = 0.016 and interleukin-6, respectively, 4.4 versus. 3.1 p/ml (p = 0.022. In general, statins were prescribed in 54,2 % of patients, among them high doses – in 17 patients (20.2 %, moderate – 46 patients (54.8 %, low – 21 patients (25 %. Conclusions. The obtained data show the insufficient level of ambulatory statins usage in patients with ischemic heart disease referred for myocardial revascularization and significant discrepancy between clinical characteristics and real statins usage. Therefore, there is a great need to determine the

  10. Safe Grid

    Science.gov (United States)

    Chow, Edward T.; Stewart, Helen; Korsmeyer, David (Technical Monitor)

    2003-01-01

    The biggest users of GRID technologies came from the science and technology communities. These consist of government, industry and academia (national and international). The NASA GRID is moving into a higher technology readiness level (TRL) today; and as a joint effort among these leaders within government, academia, and industry, the NASA GRID plans to extend availability to enable scientists and engineers across these geographical boundaries collaborate to solve important problems facing the world in the 21 st century. In order to enable NASA programs and missions to use IPG resources for program and mission design, the IPG capabilities needs to be accessible from inside the NASA center networks. However, because different NASA centers maintain different security domains, the GRID penetration across different firewalls is a concern for center security people. This is the reason why some IPG resources are been separated from the NASA center network. Also, because of the center network security and ITAR concerns, the NASA IPG resource owner may not have full control over who can access remotely from outside the NASA center. In order to obtain organizational approval for secured remote access, the IPG infrastructure needs to be adapted to work with the NASA business process. Improvements need to be made before the IPG can be used for NASA program and mission development. The Secured Advanced Federated Environment (SAFE) technology is designed to provide federated security across NASA center and NASA partner's security domains. Instead of one giant center firewall which can be difficult to modify for different GRID applications, the SAFE "micro security domain" provide large number of professionally managed "micro firewalls" that can allow NASA centers to accept remote IPG access without the worry of damaging other center resources. The SAFE policy-driven capability-based federated security mechanism can enable joint organizational and resource owner approved remote

  11. Statin use before diabetes diagnosis and risk of microvascular disease

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G

    2014-01-01

    BACKGROUND: The role of statins in the development of microvascular disease in patients with diabetes is unknown. We tested the hypothesis that statin use increases the risk of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot in individuals with diabetes...... the cumulative incidence of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, or gangrene of the foot in statin users versus non-statin users. We analysed data with Cox regression models, adjusted for covariates including sex, age at diabetes diagnosis, and method of diabetes diagnosis. To address...... diabetic neuropathy, 1248 developed diabetic nephropathy, and 2392 developed gangrene of the foot. Compared with non-statin users, statin users had a lower cumulative incidence of diabetic retinopathy (hazard ratio 0·60, 95% CI 0·54-0·66; pdiabetic neuropathy (0·66, 0·57-0·75; p

  12. Consequences of succinylcholine administration to patients using statins.

    Science.gov (United States)

    Turan, Alparslan; Mendoza, Maria L; Gupta, Shipra; You, Jing; Gottlieb, Alexandru; Chu, Weihan; Saager, Leif; Sessler, Daniel I

    2011-07-01

    Statins cause structural changes in myocytes and provoke myotoxicity, myopathy, and myalgias. Thus, patients taking statins may be especially susceptible to succinylcholine-induced muscle injury. The authors tested the hypothesis that succinylcholine increases plasma concentrations of myoglobin, potassium, and creatine kinase more in patients who take statins than in those who do not and that succinylcholine-induced postoperative muscle pain is aggravated in statin users. Patients who took statins for at least 3 months and those who had never used statins were enrolled. General anesthesia was induced and included 1.5 mg/kg succinylcholine for intubation. The incidence and degree of fasciculation after succinylcholine administration were recorded. Blood samples were obtained before induction and 5 and 20 min and 24 h after succinylcholine administration. Patients were interviewed 2 and 24 h after surgery to determine the degree of myalgia. The authors enrolled 38 patients who used statins and 32 who did not. At 20 min, myoglobin was higher in statin users versus nonusers (ratio of medians 1.34 [95% CI: 1.1, 1.7], P = 0.018). Fasciculations in statin users were more intense than in nonusers (P = 0.047). However, plasma potassium and creatine kinase concentrations were similar in statin users and nonusers, as was muscle pain. The plasma myoglobin concentration at 20 min was significantly greater in statin users than nonusers, although the difference seems unlikely to be clinically important. The study results suggest that the effect of succinylcholine given to patients taking statins is likely to be small and probably of limited clinical consequence.

  13. Efficacy of short-term high-dose statin in preventing contrast-induced nephropathy: a meta-analysis of seven randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Yongchuan Li

    Full Text Available A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathy have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of short-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of the potential benefits of statin therapy.We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statin treatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2-5 days after contrast administration and need for dialysis.Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall results based on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significant reduction in risk of CIN (RR =0.51, 95% CI 0.34-0.76, p =0.001; I(2 = 0%. The incidence of acute renal failure requiring dialysis was not significant different after the use of statin (RR = 0.33, 95% CI 0.05-2.10, p = 0.24; I(2 = 0%. The use of statin was not associated with a significant decrease in the plasma C-reactive protein level (SMD -0.64, 95% CI: -1.57 to 0.29, P = 0.18, I(2 = 97%.Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered in the context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statin based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for statin in CIN prevention.

  14. Significant improvement in statin adherence and cholesterol levels after acute myocardial infarction

    DEFF Research Database (Denmark)

    Brogaard, Hilde Vaiva Tonstad; Køhn, Morten Ganderup; Berget, Oline Sofie

    2012-01-01

    Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time.......Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time....

  15. Retrospective observational assessment of statin adherence among subjects patronizing different types of community pharmacies in Canada.

    Science.gov (United States)

    Evans, Charity D; Eurich, Dean T; Lamb, Darcy A; Taylor, Jeffrey G; Jorgenson, Derek J; Semchuk, William M; Mansell, Kerry D; Blackburn, David F

    2009-01-01

    Community pharmacies vary widely in terms of ownership structures, location, and dispensing policies. It is unknown if an association exists between the type of community pharmacy and the degree of medication adherence exhibited by patrons-patients. To describe adherence to statin therapy among subjects patronizing different types of community pharmacy categories (department- mass merchandise, chain-franchise, and independent-banner) in Saskatchewan, Canada, between 2000 and 2005. Study data were obtained from the Saskatchewan Drug Plan and Extended Benefits database, which is maintained by the government of Saskatchewan, Canada. The study included all subjects who (a) filled a statin prescription within selected community pharmacies between January 1, 2000, and December 31, 2005; (b) had no record of statin prescriptions during the year prior to the first statin prescription, according to the records of the Saskatchewan Drug Plan and Extended Benefits; and (c) demonstrated active utilization in the drug plan database for at least 1 year after the first statin prescription. The proxy criterion for activity was any dispensing record for statin or nonstatin medications at least 1 year following the index claim. Statin adherence level was estimated as tablets per day, defined as the total number of tablets dispensed divided by the total number of days of observation. Each subject's observation period began on the index date and ended on the earlier of (a) 30 days after the last recorded fill for any type of prescription medication (statin or nonstatin), or (b) December 31, 2005. The primary end point was the proportion of subjects within each pharmacy category who maintained an adherence level of 80% or greater during their individual observation period. Additional adherence calculations were performed for each of 3 time periods, beginning on the index date and ending on days 365, 729, and 1094 (i.e., 1, 2, and 3 years). Patients were included in the analysis for each

  16. Statins attenuate polymethylmethacrylate-mediated monocyte activation.

    LENUS (Irish Health Repository)

    Laing, Alan J

    2012-02-03

    BACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte\\/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

  17. HMG CoA reductase inhibitors (statins for people with chronic kidney disease not requiring dialysis

    Directory of Open Access Journals (Sweden)

    Suetonia C. Palmer

    , ESKD, elevated liver enzymes, rhabdomyolysis, cancer and withdrawal rates with 95% confidence intervals (CI. MAIN RESULTS: We included 50 studies (45,285 participants: 47 studies (39,820 participants compared statins with placebo or no treatment and three studies (5547 participants compared two different statin regimens in adults with CKD who were not yet on dialysis. We were able to meta-analyse 38 studies (37,274 participants. The risk of bias in the included studies was high. Seven studies comparing statins with placebo or no treatment had lower risk of bias overall; and were conducted according to published protocols, outcomes were adjudicated by a committee, specified outcomes were reported, and analyses were conducted using intention-to-treat methods. In placebo or no treatment controlled studies, adverse events were reported in 32 studies (68% and systematically evaluated in 16 studies (34%. Compared with placebo, statin therapy consistently prevented major cardiovascular events (13 studies, 36,033 participants; RR 0.72, 95% CI 0.66 to 0.79, all-cause mortality (10 studies, 28,276 participants; RR 0.79, 95% CI 0.69 to 0.91, cardiovascular death (7 studies, 19,059 participants; RR 0.77, 95% CI 0.69 to 0.87 and MI (8 studies, 9018 participants; RR 0.55, 95% CI 0.42 to 0.72. Statins had uncertain effects on stroke (5 studies, 8658 participants; RR 0.62, 95% CI 0.35 to 1.12. Potential harms from statin therapy were limited by lack of systematic reporting and were uncertain in analyses that had few events: elevated creatine kinase (7 studies, 4514 participants; RR 0.84, 95% CI 0.20 to 3.48, liver function abnormalities (7 studies, RR 0.76, 95% CI 0.39 to 1.50, withdrawal due to adverse events (13 studies, 4219 participants; RR 1.16, 95% CI 0.84 to 1.60, and cancer (2 studies, 5581 participants; RR 1.03, 95% CI 0.82 to 130. Statins had uncertain effects on progression of CKD. Data for relative effects of intensive cholesterol lowering in people with early stages of

  18. Association of serum lipid indices and statin consumption with periodontal status.

    Science.gov (United States)

    Sayar, F; Fallah, S; Akhondi, N; Jamshidi, S

    2016-11-01

    Periodontal and cardiovascular diseases share some common underlying mechanisms. Hyperlipidemia is a major risk factor for cardiovascular diseases. This study sought to assess the association of hyperlipidemia and statin consumption with periodontal status. This cross-sectional study was conducted on 150 participants including 50 individuals with normal lipid profile (group C), 50 hyperlipidemic patients without drug therapy (group N), and 50 hyperlipidemic patients on drug therapy for a minimum of 3 months (group S). Periodontal parameters including plaque index (PI), clinical attachment level (CAL), bleeding on probing (BOP), and pocket depth (PD) were measured for all teeth except for the third molars. Serum levels of total cholesterol (TC), HDL, LDL, and triglycerides (TGs) were measured. The mean values of CAL and PD were significantly higher in the two hyperlipidemic groups compared with the C group (P < 0.005). Also, CAL and PD had significant associations with serum levels of TGs, LDL, and TC (P < 0.0001); PI in the group S was significantly lower than that in the other groups (P < 0.005). Hyperlipidemic patients showed higher values of periodontal parameters compared with the statin-treated and control groups. Lower PI in the group S may indicate the anti-inflammatory effect of statin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. [Statins in the secondary prevention of stroke: New evidence from the SPARCL Study].

    Science.gov (United States)

    Castilla-Guerra, Luis; Fernández-Moreno, María Del Carmen; López-Chozas, José Manuel

    2016-01-01

    Until recently there was little evidence that statin therapy reduced the risk of stroke recurrence. The SPARCL trial, published in 2006, was the first trial to show the benefits of statin therapy in preventing recurrent stroke. The SPARCL trial showed that treatment with atorvastatin 80mg/day reduced recurrent stroke in patients with a recent stroke or transient ischemic attack (TIA). Several post hoc analyses of different subgroups followed the SPARCL trial. They have not revealed any significant differences when patients were grouped by age, sex or type of stroke. The SPARCL trial has also helped to identify patients who may have a greater benefit from statins: Patients with carotid stenosis, with more intense lipid lowering, and those who achieve optimal levels of LDL-C, HDL-C, triglycerides, and blood pressure. The trial has also helped to identify individuals at high risk of new vascular events. Clearly there is a before and after in stroke prevention since the SPARCL trial was published. Copyright © 2015 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Plant sterols for adults with hypercholesterolemia treated with or without medication (statins

    Directory of Open Access Journals (Sweden)

    Raquel Bernácer

    2015-07-01

    Full Text Available Hypercholesterolemia is the most common coronary risk factor among the Spanish population; 37.4% of the Spanish adult population have cholesterol levels between 190 and 240 mg/dl. Foods enriched with plant sterols (PS can effectively reduce plasma cholesterol in patients with high levels. However, its effectiveness and safety in adults with moderate hypercholesterolemia who are on medication (statins or not has been less studied. The aim of this review is to establish the possible role of plant sterols in the control of hypercholesterolemia, as well as how safe they are for people with moderate hypercholesterolemia treated with statins. The main studies were looked at, regardless of design, language or publication date which studied the connection between “plant sterols” and “hypercholesterolemia”, using Pubmed/Medline, SCOPUS and Google Scholar databases. The studies brought together in this review show that an intake of between 2 and 3g/day of plant sterols effectively reduces plasma cholesterol levels in patients with hypercholesterolemia. Both clinical studies and available meta-analyses do not indicate any problems related to the drug-nutrient interaction associated with the use of plant sterol-enriched foods. In patients with moderate hypercholesterolemia where the use of statins is not justified a healthy diet, exercise and foods high in PS can provide the best therapeutic approach.

  1. Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

    Science.gov (United States)

    Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

    2014-08-01

    Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was

  2. Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients

    DEFF Research Database (Denmark)

    Sirimarco, Gaia; Labreuche, Julien; Bruckert, Eric

    2014-01-01

    BACKGROUND AND PURPOSE: Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high......% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events...... was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14-1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06-1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95...

  3. The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis.

    Science.gov (United States)

    Liu, Binliang; Yi, Zongbi; Guan, Xiuwen; Zeng, Yi-Xin; Ma, Fei

    2017-07-01

    Breast cancer is the most common cancer in females and the leading cause of death worldwide. The effects of statins on breast cancer prognosis have long been controversial; thus, it is important to investigate the relationship between statin type, exposure time, and breast cancer prognosis. This study sought to explore the effect of statins, as well as the different effects of statin solubility and variable follow-up times, on breast cancer prognosis. We searched the MEDLINE (via PubMed), EMBASE (via OvidSP), Cochrane Library, and ISI Web of Knowledge databases using combinations of the terms "breast neoplasms[MeSH]," "statins" or "lipid-lowering drug," "prognosis" or "survival," or "mortality" or "outcome" with no limit on the publication date. We searched the databases between inception and October 15, 2016. Reference lists of the included studies and relevant reviews were also manually screened. The initial search identified 71 publications, and 7 of these studies, which included a total of 197,048 women, met the selection criteria. Two authors independently screened each study for inclusion and extracted the data. The data were analyzed using Stata/SE 11.0. Overall statin use was associated with lower cancer-specific mortality and all-cause mortality, although the benefit appeared to be constrained by statin type and follow-up time. Lipophilic statins were associated with decreased breast cancer-specific and all-cause mortality; however, hydrophilic statins were weakly protective against only all-cause mortality and not breast cancer-specific mortality. Of note, one group with more than 4 years of follow-up did not show a significant correlation between statin use and cancer-specific mortality or all-cause mortality, whereas groups with less than 4 years of follow-up still showed the protective effect of statins against cancer-specific mortality and all-cause mortality. Although statins can reduce breast cancer patient mortality, the benefit appears to be

  4. Are generic and brand-name statins clinically equivalent? Evidence from a real data-base.

    Science.gov (United States)

    Corrao, Giovanni; Soranna, Davide; Arfè, Andrea; Casula, Manuela; Tragni, Elena; Merlino, Luca; Mancia, Giuseppe; Catapano, Alberico L

    2014-10-01

    Use of generic drugs can help contain drug spending. However, there is concern among patients and physicians that generic drugs may be clinically inferior to brand-name ones. This study aimed to compare patients treated with generic and brand-name statins in terms of therapeutic interruption and cardiovascular (CV) outcomes. 13,799 beneficiaries of the health care system of Lombardy, Italy, aged 40 years or older who were newly treated with generic or brand-name simvastatin during 2008, were followed until 2011 for the occurrence of two outcomes: 1) therapeutic discontinuation and 2) hospitalization for CV events. Hazard ratios (HR) associated with use of generic or brand-name at starting therapy (intention-to-treat analysis) and during follow-up (as-treated analysis) were estimated by fitting proportional hazard Cox models. A Monte-Carlo sensitivity analysis was performed to account for unmeasured confounders. Patients who started on generic did not experience a different risk of discontinuation (HR: 0.98; 95% CI 0.94 to 1.02) nor of CV outcomes (HR: 0.98; 95% CI 0.79 to 1.22) from those starting on brand-name. Patients who spent >75% of time of follow-up with statin available on generics did not experience a different risk of discontinuation (HR: 0.94; 95% CI 0.87 to 1.01), nor of CV outcomes (HR: 1.06; 95% CI 0.83 to 1.34), compared with those who mainly or only used brand-name statin. Our findings do not support the notion that in the real world clinical practice brand-name statins are superior to generics for keeping therapy and preventing CV outcomes. Copyright © 2014. Published by Elsevier B.V.

  5. Direct to consumer Internet advertising of statins: an assessment of safety.

    Science.gov (United States)

    Williams, Bethan; Brown, David

    2012-04-01

    To evaluate a sample of Internet sites advertising statins for sale to the general public. A simulated customer search and evaluation of retrieved sites using evaluation tools focussing on quality (Q) and safe medicine use (SMU). Sites retrieved on 17 November 2010 were systematically analysed from 19 November to 23 December 2010. One hundred eighty-four sites met the inclusion criteria: 40 each for atorvastatin, pravastatin, rosuvastatin, and simvastatin and 24 for fluvastatin. Sites originated from 17 different countries. Most sites scored less than half the maximum Q score (26; range 5-17). Mean total SMU scores for each statin group were lower than 50% of the maximum (45; range of 0-28). There were no statistically significant differences between statins. General contraindications were absent in 92.4% of sites and contraindicated medicines in 47.3%. Key warnings on the appearance of symptoms associated with myopathy, liver disease, hypersensitivity, and pancreatitis were absent in 37, 48.4, 91.3, and 96.2% of sites, respectively. Most websites presented a chaotic and incomplete list of known side effects; just 13 (7.1%) presented a list compatible with current prescribing information. Only two-thirds (65.8%) attempted to describe any in lay language. A potential purchaser of statins is likely to encounter websites from a wide geographical base and of generally poor quality. This has potentially serious implications for the safety of purchasers who may not be aware of the problems associated with ordering medicines online or the actual medication, which they receive. Direct to consumer advertising websites need tighter controls. Copyright © 2012 John Wiley & Sons, Ltd.

  6. Comparison of coronary arterial lumen dimensions on angiography and plaque characteristics on optical coherence tomography images and their changes induced by statin

    International Nuclear Information System (INIS)

    Dong, Nana; Xie, Zulong; Wang, Wei; Dai, Jiannan; Sun, Meng; Pu, Zhongyue; Tian, Jinwei; Yu, Bo

    2016-01-01

    Coronary angiography (CAG) is widely used to assess lumen dimensions, and optical coherence tomography (OCT) is used to evaluate the characteristics of atherosclerotic plaque. This study was aimed to compare coronary lumen dimensions using CAG and plaque characteristics using OCT and their changes during statin therapy. We identified 97 lipid-rich plaques from 69 statin-naïve patients, who received statin therapy in the following 12 months. CAG and OCT examinations were conducted at baseline and 12-month follow-up period. Lesion length, as measured by CAG, was closely correlated with lipid length by OCT (baseline: r = 0.754, p < 0.001; follow-up: r = 0.639, p < 0.001). However, no significant correlations were found between the other findings on OCT and data on CAG. With 12-month statin therapy, microstructures of lipid-rich plaques were significantly improved, but CAG-derived lumen dimensions were not improved. Moreover, we found no significant relationship between changes in OCT measurements and changes in CAG data over time. Lipid length on OCT and lesion length on CAG were closely correlated. However, plaque microstructural characteristics on OCT showed no significantly statistically correlations with lumen dimensions on CAG, neither did their evolutionary changes induced by statin over time. Clinical trial registry: ClinicalTrial.gov. Registered number: NCT01023607. Registered 1 December 2009

  7. Prevalence of dyslipidaemia in statin-treated patients in Ireland: Irish results of the DYSlipidaemia International Study (DYSIS).

    LENUS (Irish Health Repository)

    Horgan, S

    2012-02-01

    BACKGROUND: Statins are proven to reduce cardiovascular risk; however, substantial risk remains in patients on statin therapy. Persisting dyslipidaemia is likely to play a contributory role. AIM: To assess the prevalence of persisting lipid abnormalities in patients treated with statins. METHODS: DYSIS was a cross-sectional study of 22,063 patients in Europe and Canada. 900 Irish patients participated. All patients were >\\/= 45 years and treated with statins for >\\/= 3 months. Data were collected from the patients\\' records. ESC guidelines were used to classify risk and to define lipid levels. RESULTS: Mean age was 66.1 years with women representing 40.7%. 78.6% were high-risk patients; that is 53.9% with cardiovascular disease (CVD), 20.1% with diabetes and 15.9% with a SCORE risk >\\/= 5%. Total cholesterol was not at goal in 34.4% of all patients. LDL-C was elevated in 30.8% of all patients and in 30% at high risk. Low HDL-C was found in 34.7% of high-risk patients compared to 16.9% of patients with an ESC score <5%. In diabetics without CVD, low HDL-C and elevated TGs were found in 46 and 44.3%, respectively. CONCLUSIONS: Despite statin therapy, a significant number of patients have persistent dyslipidaemia. While LDL-C targets are suboptimal in three out of ten patients, the prevalence of low HDL-C and high TGs in high-risk patients is greater than one in three. A more integrated approach to the treatment of patients with dyslipidaemia is warranted. Clinical trials are needed to assess the impact of therapies that raise HDL-C and lower elevated TGs.

  8. Statin and Atrial Fibrilation: When does it work?

    Science.gov (United States)

    Fauchier, Laurent; Clementy, Nicolas; Pierre, Bertrand; Babuty, Dominique

    2012-01-01

    In the recent years, some clinical and experimental studies have suggested that the use of statins may protect against atrial fibrillation (AF). A relation between inflammation and the development of AF has been described, and the potent anti-inflammatory and antioxidant properties of statins may make them effective in preventing the development of AF. A global analysis of the literature suggests that the use of statins is associated with a decreased risk of incidence or recurrence of AF in some cases. However, this beneficial effect is not seen for all types of AF in all the patients. The use of statins seems associated 1) with a lack of benefit in primary prevention of AF, 2) with a significant but heterogeneous decreased risk of recurrence of AF in secondary prevention, and 3) with a very significant and homogeneous reduction for the risk of post operative AF. An intensive lipid lowering statin regimen does not provide greater protection against AF. Patients with coronary heart disease are curr ently treated with statins in most cases, and this may not have an impact on their treatment. In contrast, it remains to determine more accurately if statins may bring a significant benefit for some AF patients without any type of established atherosclerotic disease or with a low risk of atherogenesis. Since it remains uncertain whether the suppression of AF in these patients is beyond doubt beneficial, prescribing statins for this purpose alone should not be recommended at the present time.

  9. Price and utilisation differences for statins between four countries.

    Science.gov (United States)

    Thai, Loc Phuoc; Vitry, Agnes Isabelle; Moss, John Robert

    2018-02-01

    Australia, England, France and New Zealand use different policies to regulate their medicines market, which can impact on utilisation and price. To compare the prices and utilisation of statins in Australia, England, France and New Zealand from 2011 to 2013. Utilisation of statins in the four countries was compared using Defined Daily Doses (DDD) per 1000 inhabitants per year. Pairwise Laspeyres and Paasche index comparisons were conducted comparing the price and utilisation of statins. The results showed that the price of statins in New Zealand was the cheapest. The price of statins in Australia was most expensive in 2011 and 2012 but France was more expensive in 2013. There were large differences between the Laspeyres index and Paasche index when comparing the price and utilisation of England with Australia and France. The policies that regulate the New Zealand and England medicines markets were more effective in reducing the price of expensive statins. The relative utilisation of cheaper statins was greatest in England and had a large effect on the differences between the two index results. The pricing policies in Australia have been only partly effective in reducing the price of statins compared to other countries.

  10. Statin drug-drug interactions in a Romanian community pharmacy.

    Science.gov (United States)

    Badiu, Raluca; Bucsa, Camelia; Mogosan, Cristina; Dumitrascu, Dan

    2016-01-01

    Statins are frequently prescribed for patients with dyslipidemia and have a well-established safety profile. However, when associated with interacting dugs, the risk of adverse effects, especially muscular toxicity, is increased. The objective of this study was to identify, characterize and quantify the prevalence of the potential drug-drug interactions (pDDIs) of statins in reimbursed prescriptions from a community pharmacy in Bucharest. We analyzed the reimbursed prescriptions including statins collected during one month in a community pharmacy. The online program Medscape Drug Interaction Checker was used for checking the drug interactions and their classification based on severity: Serious - Use alternative, Significant - Monitor closely and Minor. 132 prescriptions pertaining to 125 patients were included in the analysis. Our study showed that 25% of the patients who were prescribed statins were exposed to pDDIs: 37 Serious and Significant interactions in 31 of the statins prescriptions. The statins involved were atorvastatin, simvastatin and rosuvastatin. Statin pDDIs have a high prevalence and patients should be monitored closely in order to prevent the development of adverse effects that result from statin interactions.

  11. Postoperative atrial fibrillation in patients on statins undergoing ...

    African Journals Online (AJOL)

    LW Drummond

    2013-04-02

    Apr 2, 2013 ... neurocognitive impairment8,9 and prolonged hospitalisation.2,5,6,7,9. The prevention of ... cohorts.12 However, what is uncertain is whether or not statin ... unless contraindicated (class 1 recommendation, level of evidence A).13 ... statins which were started in the preoperative period specifically with the ...

  12. Disappearance of statin following serum-stimulated cell cycle entry

    International Nuclear Information System (INIS)

    Wang, E.; Lin, S.L.

    1986-01-01

    Statin, a protein of 57,000 D, is present in the nuclei of quiescent of senescent fibroblasts, but is absent in their young replicating counterparts. Immunohistochemical survey of a variety of tissues demonstrates that the presence of statin is a marker for cells that are no longer involved in proliferation, i.e. those cells that are terminally differentiated. Statin expression was examined by immunofluorescence microscopy in serum-starved cultures whose replication had been reinitiated by raising the serum concentration from 0.5 to 10%. Prior to serum addition, more than 85% of the cells stained positively for statin. After stimulation with serum, the expression of statin disappeared rapidly within the first 12-14 h. On the other hand, and increase in the level of DNA synthesis, signifying entry into S phase, was observed initially at 18 h after serum stimulation, and reached maximal levels 6h later. Immunoprecipitation of statin derived from cells harvested at different intervals after serum stimulation revealed that the level of statin synthesis was reduced by 4 h and was hardly detectable at 8 h. These results demonstrate that (1) the synthesis of statin occurs primarily when cells are in a quiescent state, and declines rapidly when cells are induced to proliferate; (2) this decline precedes the transition from G1 to S phase

  13. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

  14. Changes in muscle strength in patients with statin myalgia.

    Science.gov (United States)

    Panza, Gregory A; Taylor, Beth A; Roman, William; Thompson, Paul D

    2014-10-15

    Statins can produce myalgia or muscle pain, which may affect medication adherence. We measured the effects of statins on muscle strength in patients with previous statin myalgia. Leg isokinetic extension average power at 60° per second (-8.8 ± 10.5N-M, p = 0.02) and average peak torque at 60° per second (-14.0 ± 19.7N-M, p = 0.04) decreased slightly with statin use, but 8 of 10 other variables for leg strength did not change (all p >0.13). Handgrip, muscle pain, respiratory exchange ratio, and daily activity also did not change (all p >0.09). In conclusion, statin myalgia is not associated with reduced muscle strength or muscle performance. Published by Elsevier Inc.

  15. The effect of coenzyme Q10 in statin myopathy.

    Science.gov (United States)

    Zlatohlavek, Lukas; Vrablik, Michal; Grauova, Barbora; Motykova, Eva; Ceska, Richard

    2012-01-01

    Statins significantly reduce CV morbidity and mortality. Unfortunately, one of the side effects of statins is myopathy, for which statins cannot be administered in sufficient doses or administered at all. The aim of this study was to demonstrate the effect of coenzyme Q10 in patients with statin myopathy. Twenty eight patients aged 60.6±10.7 years were monitored (18 women and 10 men) and treated with different types and doses of statin. Muscle weakness and pain was monitored using a scale of one to ten, on which patients expressed the degree of their inconvenience. Examination of muscle problems was performed prior to administration of CQ10 and after 3 and 6 months of dosing. Statistical analysis was performed using Friedman test, Annova and Students t-test. Pain decreased on average by 53.8% (pmuscle weakness by 44.4% (pmuscle pain and sensitivity statistically significantly decreased.

  16. Können Statine den Knochenstoffwechsel positiv beeinflussen?

    Directory of Open Access Journals (Sweden)

    Vock L

    2005-01-01

    Full Text Available Statine, potente Inhibitoren der HMG-CoA-Reduktase, werden erfolgreich zur Senkung der Cholesterinblutspiegel eingesetzt. In den letzten Jahren sind jedoch zahlreiche andere Wirkungen der Statine aufgedeckt worden, die möglicherweise für den Knochenstoffwechsel von Bedeutung sind: In vitro konnten faszinierende knochenanabole Wirkungen der Statine bewiesen werden. Welche molekularen Mechanismen für diese Beobachtungen genau verantwortlich sind, ist nach wie vor unklar. Auch konnten in anderen In-vitro-Studien, Tiermodellen und klinischen Studien diese eindrucksvollen Resultate nicht immer bestätigt werden. Das vorliegende Bild der Statine im Knochenstoffwechsel ist uneinheitlich. Viele Fragen bleiben offen. Es fehlen neben genaueren Erkenntnissen über die Eigenschaften der einzelnen Statine auch Resultate besser auf diese Fragestellung zugeschnittener Studien.

  17. Low vitamin D does not predict statin associated muscle symptoms but is associated with transient increases in muscle damage and pain.

    Science.gov (United States)

    Taylor, Beth A; Lorson, Lindsay; White, C Michael; Thompson, Paul D

    2017-01-01

    Low vitamin D (VITD) may contribute to statin-associated muscle symptoms (SAMS). We examined the influence of baseline and change in VITD in patients with verified SAMS. SAMS was verified in 120 patients with prior statin muscle complaints using 8-week randomized, double-blind crossover trials of simvastatin (SIMVA) 20 mg/d and placebo. 25 (OH)vitamin D was measured at each phase of the trial. Forty-three patients (35.8%) experienced muscle pain on SIMVA but not placebo, exhibiting confirmed SAMS. VITD (mean ± standard deviation) prior to SIMVA treatment was not different between patients who did (31.7 ± 12.1 ng/mL, n = 43) or did not (31.6 ± 10.3 ng/mL, n = 77) develop SAMS and did not predict SAMS (p = 0.96). The change in VITD with SIMVA treatment was not different between patients with and without SAMS (0.3 ± 5.9 vs. 0.2 ± 8.3 ng/mL, respectively) and did not predict SAMS (p = 0.96). The proportion of patients classified as VITD deficient (statin VITD were inversely related to the change in creatine kinase (CK) with statin therapy (p = 0.01 and 0.02, respectively), independent of SAMS (p = 0.36 and 0.35). Baseline VITD, VITD deficiency/insufficiency and changes in VITD with statin therapy do not predict SAMS in patients with rigorously verified SAMS. However, low VITD may exacerbate statin-induced muscle injury and could contribute to SAMS development with a longer duration of statin treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin

    International Nuclear Information System (INIS)

    Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Liantonio, Antonella; Musaraj, Kejla; Cannone, Maria; Fonzino, Adriano; Giustino, Arcangela; De Luca, Annamaria; Romano, Rossella; Camerino, Claudia; Laghezza, Antonio; Loiodice, Fulvio; Desaphy, Jean-Francois; Conte Camerino, Diana; Pierno, Sabata

    2016-01-01

    -related changes of energy production contribute to statin-induced myotoxicity. • These findings suggest caution with statin therapy during aging.

  19. Statin-induced myotoxicity is exacerbated by aging: A biophysical and molecular biology study in rats treated with atorvastatin

    Energy Technology Data Exchange (ETDEWEB)

    Camerino, Giulia Maria; De Bellis, Michela; Conte, Elena; Liantonio, Antonella; Musaraj, Kejla; Cannone, Maria; Fonzino, Adriano [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Giustino, Arcangela [Department of Biomedical Sciences and Human Oncology, University of Bari - Aldo Moro, Medical School, Bari (Italy); De Luca, Annamaria; Romano, Rossella [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Camerino, Claudia [Department of Medical Sciences, Neurosciences and Sense Organs, University of Bari - Aldo Moro, Bari (Italy); Laghezza, Antonio; Loiodice, Fulvio [Section of Medicinal Chemistry, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Desaphy, Jean-Francois [Department of Biomedical Sciences and Human Oncology, University of Bari - Aldo Moro, Medical School, Bari (Italy); Conte Camerino, Diana [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy); Pierno, Sabata, E-mail: sabata.pierno@uniba.it [Section of Pharmacology, Department of Pharmacy & Drug Sciences, University of Bari - Aldo Moro, Bari (Italy)

    2016-09-01

    -related changes of energy production contribute to statin-induced myotoxicity. • These findings suggest caution with statin therapy during aging.

  20. Safe cycling!

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    The HSE Unit will be running a cycling safety campaign at the entrances to CERN's restaurants on 14, 15 and 16 May. Pop along to see if they can persuade you to get back in the saddle!   With summer on its way, you might feel like getting your bike out of winter storage. Well, the HSE Unit has come up with some original ideas to remind you of some of the most basic safety rules. This year, the prevention campaign will be focussing on three themes: "Cyclists and their equipment", "The bicycle on the road", and "Other road users". This is an opportunity to think about the condition of your bike as well as how you ride it. From 14 to 16 May, representatives of the Swiss Office of Accident Prevention and the Touring Club Suisse will join members of the HSE Unit at the entrances to CERN's restaurants to give you advice on safe cycling (see box). They will also be organising three activity stands where you can test your knowle...

  1. The effect of statin treatment on the prevention of stent mediated flow limited edge dissections during PCI in patients with stable angina.

    Science.gov (United States)

    Oksuz, Fatih; Yarlioglues, Mikail; Yayla, Cagrı; Canpolat, Ugur; Murat, Sani Namık; Aydogdu, Sinan

    2016-10-01

    The effect of statin therapy before PCI with direct stenting may reduce the development of flow limited edge dissections (ED) in patients with stable angina. Flow limited ED after PCI is associated with an increased risk of major adverse cardiovascular events. Statin therapy induces important changes in the plaque composition which have been previously identified as strong predictors of ED. 100 patients complicated with flow limited ED and 100 control patients with successful procedure were enrolled into the study. EDs were described as the 5-mm regions that were immediately adjacent to the stent borders, both distally and proximally on the coronary angiography. Rate of statin use and duration of statin use were significantly higher in patients with non-ED group (63%) versus ED group (25%) (p<0.001). In addition, patients in ED group had significantly higher levels of C-reactive protein (CRP) at admission (9.9mg/dL (5.89-16.45) vs. 4.40mg/dL (3.5-7.09), respectively, p=0.014). Our findings suggested that maintenance statin treatment before PCI with direct stenting may reduce the development of flow limited ED in patients with stable angina. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Role of integrin-linked kinase in vascular smooth muscle cells: Regulation by statins and angiotensin II

    International Nuclear Information System (INIS)

    Friedrich, Erik B.; Clever, Yvonne P.; Wassmann, Sven; Werner, Nikos; Boehm, Michael; Nickenig, Georg

    2006-01-01

    Our goal was to characterize the role of integrin-linked kinase (ILK) in vascular smooth muscle cells (VSMC), which play a crucial role in atherogenesis. Transfection of VSMC with wild-type and dominant-negative ILK cDNA constructs revealed that ILK mediates migration and proliferation of VSMC but has no effect on VSMC survival. The pro-atherogenic mediator angiotensin II increases ILK protein expression and kinase activity while statin treatment down-regulates ILK in VSMC. Functionally, ILK is necessary for angiotensin II-mediated VSMC migration and proliferation. In VSMC transduced with dominant-negative ILK, statins mediate an additive inhibition of VSMC migration and proliferation, while transfection with wild-type ILK is sufficient to overcome the inhibitory effects of statin treatment on VSMC migration and proliferation. In vivo, ILK is expressed in VSMC of aortic sections from wild-type mice where it is down-regulated following statin treatment and up-regulated following induction of atherosclerosis in apoE-/- mice. These data identify ILK as a novel target in VSMC for anti-atherosclerotic therapy

  3. The Effect of Statins on Skeletal Muscle Function

    Science.gov (United States)

    Parker, Beth A.; Capizzi, Jeffrey A.; Grimaldi, Adam S.; Clarkson, Priscilla M.; Cole, Stephanie M.; Keadle, Justin; Chipkin, Stuart; Pescatello, Linda S.; Simpson, Kathleen; White, C. Michael; Thompson, Paul D.

    2015-01-01

    Background Many clinicians believe that statins cause muscle pain, but this has not been observed in clinical trials and the effect of statins on muscle performance has not been carefully studied. Methods and Results The Effect of STatins On Skeletal Muscle Function and Performance (STOMP) study assessed symptoms and measured creatine kinase (CK), exercise capacity, and muscle strength before and after atorvastatin 80 mg or placebo were administered for 6 months to 420 healthy, statin-naive subjects. No individual CK value exceeded 10 times normal, but average CK increased 20.8 ± 141.1 U/L (pmuscle strength or exercise capacity with atorvastatin, but more atorvastatin than placebo subjects developed myalgia (19 vs 10; p = 0.05). Myalgic subjects on atorvastatin or placebo decreased muscle strength in 5 of 14 and 4 of 14 variables respectively (p = 0.69). Conclusions These results indicate that high-dose atorvastatin for 6 months does not decrease average muscle strength or exercise performance in healthy, previously untreated subjects. Nevertheless, this blinded, controlled trial confirms the undocumented impression that statins increase muscle complaints. Atorvastatin also increased average CK suggesting that statins produce mild muscle injury even among asymptomatic subjects. This increase in CK should prompt studies examining the effects of more prolonged, high-dose statin treatment on muscular performance. Clinical Trial Registration Information: www.clinicaltrials.gov; Identifier: NCT00609063. PMID:23183941

  4. Statins and oxidative stress in the cardiovascular system.

    Science.gov (United States)

    Margaritis, Marios; Sanna, Fabio; Antoniades, Charalambos

    2017-09-26

    Statins are widely established as an important class of medications for primary and secondary prevention of cardiovascular disease. In addition to their lipid-lowering effects, mounting evidence suggests that statins exhibit non-lipid-lowering mediated effects in the cardiovascular system. These so called "pleiotropic" effects are partly due to antioxidant properties of statins. These are mediated by inhibition of the mevalonate pathway, which interferes with small GTP-ase protein prenylation. This, in turn, leads to anti-oxidant effects of statins via a plethora of mechanisms. Statins prevent the activation of the pro-oxidant enzyme NADPH-oxidase by interfering with Rac1 activation and translocation to the membrane, as well as reducing expression of crucial subunits of NADPH-oxidase. Statins also enhance the expression, enzymatic activity and coupling of endothelial nitric oxide synthase (eNOS), through mevalonate-dependent effects. The net result is a restoration of the redox balance in the cardiovascular system, with subsequent anti-atherosclerotic and cardioprotective effects. While the evidence from basic science studies and animal models is strong, more clinical trials are required to establish the relevance of these pleiotropic effects to human cardiovascular disease and potentially lead to expanded indications for statin treatment or alternative therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Impact of statins on risk of new onset diabetes mellitus: a population-based cohort study using the Korean National Health Insurance claims database

    Directory of Open Access Journals (Sweden)

    Lee J

    2016-10-01

    Full Text Available Jimin Lee,1 Yoojin Noh,1 Sooyoung Shin,1 Hong-Seok Lim,2 Rae Woong Park,3 Soo Kyung Bae,4 Euichaul Oh,4 Grace Juyun Kim,5 Ju Han Kim,5 Sukhyang Lee1 1Division of Clinical Pharmacy, College of Pharmacy, Ajou University, Suwon, South Korea; 2Department of Cardiology, School of Medicine, Ajou University, Suwon, South Korea; 3Department of Biomedical Informatics, School of Medicine, Ajou University, Suwon, South Korea; 4Division of Pharmaceutical Sciences, College of Pharmacy, The Catholic University of Korea, Bucheon, South Korea; 5Division of Biomedical Informatics, College of Medicine, Seoul National University, Seoul, South Korea Abstract: Statin therapy is beneficial in reducing cardiovascular events and mortalities in patients with atherosclerotic cardiovascular diseases. Yet, there have been concerns of increased risk of diabetes with statin use. This study was aimed to evaluate the association between statins and new onset diabetes mellitus (NODM in patients with ischemic heart disease (IHD utilizing the Korean Health Insurance Review and Assessment Service claims database. Among adult patients with preexisting IHD, new statin users and matched nonstatin users were identified on a 1:1 ratio using proportionate stratified random sampling by sex and age. They were subsequently propensity score matched further with age and comorbidities to reduce the selection bias. Overall incidence rates, cumulative rates and hazard ratios (HRs between statin use and occurrence of NODM were estimated. The subgroup analyses were performed according to sex, age groups, and the individual agents and intensities of statins. A total of 156,360 patients (94,370 in the statin users and 61,990 in the nonstatin users were included in the analysis. The incidence rates of NODM were 7.8% and 4.8% in the statin users and nonstatin users, respectively. The risk of NODM was higher among statin users (crude HR 2.01, 95% confidence interval [CI] 1.93–2.10; adjusted HR 1

  6. Statin use and peripheral sensory perception: a pilot study.

    Science.gov (United States)

    West, Brenton; Williams, Cylie M; Jilbert, Elise; James, Alicia M; Haines, Terry P

    2014-06-01

    Peripheral sensory neuropathy is a neurological deficit resulting in decreased detection of sensation through the peripheral nervous system. Peripheral sensory neuropathy is commonly diagnosed with the use of a monofilament and either a tuning fork or neurothesiometer. Statins are a widely used medication and there has been some debate of association with their use and peripheral sensory neuropathy. This pilot study aimed to test the sensory perception of participants with long-term statin use and compare these results to their peers who were not taking statins. Thirty participants were recruited and equally divided into a statin and non-statin group. Healthy participants were screened by their medical and medication history, Australian Type 2 Diabetes Risk assessment, and random blood glucose level. An assessor who was blinded to the participant group conducted sensory assessments using a 10 g monofilament and neurothesiometer. There was no difference in monofilament testing results between the groups. The statin group was less sensate at the styloid process (p = 0.031) and medial malleolus (p = 0.003) than the control group. Results at the hallux were not statistically significant (p = 0.183). This result is suggestive of a potential association between long-term statin use and a decrease in peripheral sensory perception. This may be because of peripheral sensory neuropathy. Limitations such as consideration of participant height, participant numbers, and inability to analyze results against statin groups are reported. As statins are a life-saving medication, careful consideration should be applied to these results and further research be conducted to determine if these results are applicable to larger populations.

  7. Metabolic syndrome is associated with muscle symptoms among statin users.

    Science.gov (United States)

    Brinton, Eliot A; Maki, Kevin C; Jacobson, Terry A; Sponseller, Craig A; Cohen, Jerome D

    2016-01-01

    Muscle symptoms have been associated with statin use, but the relationship of statin-associated muscle symptoms with metabolic syndrome (MS) has not been reported previously. To evaluate the relationships between MS and its individual components with statin-associated muscle symptoms. Data were analyzed from the Understanding Statin Use in America and Gaps in Education (USAGE) study. Modified criteria to define the MS were used based on self-reported survey data. Among USAGE subjects, the MS was present in 1364 of 3992 men (34.2%) and in 1716 women of 6149 women (27.9%). Subjects with the MS were 19% more likely (P = .0002) to report new or worsening muscle symptoms while on a statin. Three MS criteria-increased BMI, elevated triglycerides (TG), and low high-density lipoprotein cholesterol (HDL-C)-were associated with increased odds of muscle symptoms, by 18%, 32%, and 28%, respectively (all P statin due to muscle symptoms (13% higher, P = .043). Among criteria for the MS, elevated TG (38% higher odds, P statin discontinuation, whereas hypertension (13% lower odds, P = .019) and diabetes mellitus (12% lower odds, P = .036) were inversely associated. USAGE participants with MS were more likely to report experiencing muscle symptoms while taking a statin and to have discontinued a statin due to muscle symptoms. This appears to be attributable mainly to associations of muscle symptoms with elevated TG and low HDL-C levels. Additional research is warranted to confirm and further investigate these associations. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  8. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Alizadeh, Moein [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Sylvestre, Marie-Pierre [Research Center, Department of Statistics, University of Montreal, Montreal, Quebec (Canada); Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Taussky, Daniel, E-mail: daniel.taussky.chum@ssss.gouv.qc.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada)

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  9. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    International Nuclear Information System (INIS)

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-01-01

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level 20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08–0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02–0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  10. How safe is safe enough?

    International Nuclear Information System (INIS)

    Desnoyers, B.; Chanzy, Y.

    2004-01-01

    The IAEA Regulations for the Safe Transport of Radioactive Material, were historically established with the objective to reduce the probability that persons be exposed to unacceptable doses due to normal operation or accident situations during transport of radioactive material. Based on the International Basic Safety Standards for Protection against Ionizing Radiation (BSS), the definition, which was adopted for an unacceptable dose for an accident situation, is the excess of the maximum dose limits permissible in a single year for the occupational exposure of a worker in the BSS. Concerning the severity of accident situations, it has always be clearly stated that the objective of the tests for demonstrating ability to withstand accident conditions of transport was not to cover every accident condition, but solely most of them. The last available evaluations regarding the rate of accidents which are covered by the standardised accident conditions of transport defined in the IAEA Regulations give a range of about 80%, plus or minus 15% which depends on transport mode and studies. Consequently, slight variations in the capabilities of the packages to meet the specified performance would probably not have significant consequences on the protection level in case of accident. In the assessment of the compliance with the regulations, the tendency of experts, taking advantage of the enhanced performances of computer calculation codes, is to ask more and more calculations, with more and more accuracy, leading to more and more restrictions. Consequently, cost and delay are considerably increased without any evidence of an equivalent effect on the level of protection. This paper will initiate a reflection on the general objectives and principles when implementing the Regulations, in such a way that demonstrations remain cost effective, taking into account evolution of the techniques and a high level of safety

  11. Plasma PCSK9 levels are significantly modified by statins and fibrates in humans

    Directory of Open Access Journals (Sweden)

    Mbikay Majambu

    2008-06-01

    Full Text Available Abstract Background Proprotein convertase subtilisin kexin-like 9 (PCSK9 is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC by negatively regulating low density lipoprotein receptor (LDLR levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men. Results Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013. Atorvastatin administration (HMGCoA reductase inhibitor significantly increased plasma PCSK9 (7.40%, p = 0.033 and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012. Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6× vs 1.5×, respectively at 10 μM, while fenofibrate did not induce changes in either. Conclusion These results suggest that in vivo (1 statins directly increase PCSK9 expression while (2 fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3 that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy

  12. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality

    DEFF Research Database (Denmark)

    Nielsen, Sune Fallgaard; Nordestgaard, Børge Grønne

    2016-01-01

    .03-1.06) for male sex, 1.13 (1.11-1.15) for living in cities, 1.67 (1.63-1.71) for other ethnicity than Danish, 0.92 (0.90-0.94) for positive statin-related news stories, 0.73 (0.72-0.74) for baseline cardiovascular disease, and 0.91 (0.90-0.93) for baseline diabetes. During follow-up, the hazard ratios...

  13. Cardiovascular disease guideline adherence and self-reported statin use in longstanding type 1 diabetes: results from the Canadian study of longevity in diabetes cohort.

    Science.gov (United States)

    Bai, Johnny W; Boulet, Geneviève; Halpern, Elise M; Lovblom, Leif E; Eldelekli, Devrim; Keenan, Hillary A; Brent, Michael; Paul, Narinder; Bril, Vera; Cherney, David Z I; Weisman, Alanna; Perkins, Bruce A

    2016-01-25

    Older patients with longstanding type 1 diabetes have high cardiovascular disease (CVD) risk such that statin therapy is recommended independent of prior CVD events. We aimed to determine self-reported CVD prevention guideline adherence in patients with longstanding diabetes. 309 Canadians with over 50 years of type 1 diabetes completed a medical questionnaire for presence of lifestyle and pharmacological interventions, stratified into primary or secondary CVD prevention subgroups based on absence or presence of self-reported CVD events, respectively. Associations with statin use were analyzed using multivariable logistic regression. The 309 participants had mean ± SD age 65.7 ± 8.5 years, median diabetes duration 54.0 [IQR 51.0, 59.0] years, and HbA1c of 7.5 ± 1.1 % (58 mmol/mol). 159 (52.7 %) participants reported diet adherence, 296 (95.8 %) smoking avoidance, 217 (70.5 %) physical activity, 218 (71.5 %) renin-angiotensin-system inhibitor use, and 220 (72.1 %) statin use. Physical activity was reported as less common in the secondary prevention subgroup, and current statin use was significantly lower in the primary prevention subgroup (65.5 % vs. 84.8 %, p = 0.0004). In multivariable logistic regression, the odds of statin use was 0.38 [95 % CI 0.15-0.95] in members of the primary compared to t