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Sample records for statin treatment assessed

  1. Statin treatment in multiple sclerosis

    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...

  2. STATIN CONTAINING COMPOSITIONS FOR TREATMENT OF CANCER

    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.

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

    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

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

    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.

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

    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.

  6. Comparison of the efficacy and safety of intensive-dose and standard-dose statin treatment for stroke prevention

    Wang, Juan; Chen, Dan; Li, Da-Bing; Yu, Xin; Shi, Guo-Bing

    2016-01-01

    Abstract Background: Previous study indicated that high-dose statin treatment might increase the risk of hemorrhagic stroke and adverse reactions. We aim to compare the efficacy and safety of intensive-dose and standard-dose statin treatment for preventing stroke in high-risk patients. Methods: A thorough search was performed of multiple databases for publications from 1990 to June 2015. We selected the randomized clinical trials comparing standard-dose statin with placebo and intensive-dose statin with standard-dose statin or placebo for the prevention of stroke events in patients. Duplicate independent data extraction and bias assessments were performed. Data were pooled using a fixed-effects model or a random-effects model if significant heterogeneity was present. Results: For the all stroke incidences, intensive-dose statin treatment compared with placebo treatment and standard-dose statin treatment compared with placebo treatment showed a significant 21% reduction in relative risk (RR) (RR 0.79, 95% confidence interval (CI) [0.71, 0.87], P statin treatment compared with standard dose or placebo was effective reducing fatal stroke (RR 0.61, 95% CI [0.39, 0.96], P = 0.03) and the RR was 1.01 (95% CI [0.85, 1.20], P = 0.90) in standard-dose statin treatment compared with placebo. Conclusion: The results of this meta-analysis suggest that intensive-dose statin treatment might be more favorable for reducing the incidences of all strokes than standard-dose statin treatment, especially for patients older than 65 years in reducing the incidences of all stroke incidences. PMID:27684837

  7. Can treatment with statins have a negative influence on the tolerance of mandibular advancement devices?

    González, Mónica; Macias-Escalada, Emilio; Cobo, Juan; Fernández Mondragón, Maria Pilar; Gómez-Moreno, Gerardo; Martínez-Martínez, Marian; de Carlos, Felix

    2016-12-01

    Statins are considered the most effective drugs used in the treatment of dyslipidemias. Some of their adverse effects are related to muscle problems. Myalgias produced by statins appear more often during exercise. Mandibular advancement devices (MAD) force the propulsory and elevatory musculature of the mandible to exercise by making the jaw move forward. The aim of this study is to evaluate the incidence of muscular side effects (referred, spontaneous, or under palpation pain, myofascial pain, mandibular rigidity and fatigue, tension and sensitivity of the masticatory muscles) in a group of patients with a diagnosis of obstructive sleep apnea being treated with MAD. This was a prospective study, involving consecutively 104 patients with a diagnosis of OSAS, and who had begun treatment with a custom made oral device. Muscular side effects were collected by anamnesis (verbal request and questionnaires), psychological status and clinical assessment (manual muscle palpation in the masticatory and cervical muscle groups), before and during MAD treatment. Of the total sample, 22.1 % presented muscular side effects with the oral device. However, in patients taking statins, this percentage was 57.1 %, as opposed to 16.7 % of the non-statins patients (p statin patients (odds ratio 6.67, p = 0.002). Treatment with statins can give rise to the appearance of undesirable side effects among patients being treated with oral devices.

  8. Influence of statin treatment on coronary atherosclerosis visualised using multidetector computed tomography

    Hoffmann, Hans [Charite, Medical School, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Radiology, Berlin (Germany); Klinikum Brandenburg, Department of Cardiology, Angiology, and Pulmonology, Brandenburg an der Havel (Germany); Frieler, Katja [Charite, Medical School, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Medical Statistics, Berlin (Germany); Potsdam Institut fuer Klimaforschung, Potsdam (Germany); Schlattmann, Peter [Charite, Medical School, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Medical Statistics, Berlin (Germany); Hamm, Bernd [Charite, Medical School, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Radiology, Berlin (Germany); Dewey, Marc [Charite, Medical School, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Radiology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Freie Universitaet Berlin and Humboldt-Universitaet zu Berlin, Department of Radiology (Germany)

    2010-12-15

    Coronary angiography using multidetector computed tomography (MDCT) allows non-invasive assessment of non-calcified, calcified and mixed plaques. Progression of coronary plaques may be influenced by statins. Sixty-three consecutive patients underwent MDCT as a follow-up to their original CT angiography in a retrospective longitudinal study. MDCT was performed by using a voxel size of 0.5 x 0.35 x 0.35 mm{sup 3} at two time points 25 {+-} 3 months apart. Non-calcified, calcified and mixed coronary plaque components were analysed by using volumetric measurement. The influence of statin, low-density lipoprotein (LDL) and risk factors was assessed by using a linear random intercept model for plaque growth. The volumes of non-calcified, calcified and mixed coronary plaques significantly (P < 0.001) increased from baseline (medians/interquartile ranges = 21/15-39, 7/3-20 and 36/16-69 mm{sup 3}) to follow-up (29/17-44, 13/6-29 and 41/20-75 mm{sup 3}). Statins significantly slowed the growth of non-calcified plaques (statin coefficient {beta} = -0.0036, P = 0.01) but did not significantly affect the growth rate of mixed or calcified plaques. The effect of statin treatment on non-calcified plaques remained significant after adjusting for LDL levels and cardiac risk factors. Quantification using MDCT shows that progression of non-calcified coronary plaques may be slowed by statins. (orig.)

  9. Influence of statin treatment on coronary atherosclerosis visualised using multidetector computed tomography

    Hoffmann, Hans; Frieler, Katja; Schlattmann, Peter; Hamm, Bernd; Dewey, Marc

    2010-01-01

    Coronary angiography using multidetector computed tomography (MDCT) allows non-invasive assessment of non-calcified, calcified and mixed plaques. Progression of coronary plaques may be influenced by statins. Sixty-three consecutive patients underwent MDCT as a follow-up to their original CT angiography in a retrospective longitudinal study. MDCT was performed by using a voxel size of 0.5 x 0.35 x 0.35 mm 3 at two time points 25 ± 3 months apart. Non-calcified, calcified and mixed coronary plaque components were analysed by using volumetric measurement. The influence of statin, low-density lipoprotein (LDL) and risk factors was assessed by using a linear random intercept model for plaque growth. The volumes of non-calcified, calcified and mixed coronary plaques significantly (P 3 ) to follow-up (29/17-44, 13/6-29 and 41/20-75 mm 3 ). Statins significantly slowed the growth of non-calcified plaques (statin coefficient β = -0.0036, P = 0.01) but did not significantly affect the growth rate of mixed or calcified plaques. The effect of statin treatment on non-calcified plaques remained significant after adjusting for LDL levels and cardiac risk factors. Quantification using MDCT shows that progression of non-calcified coronary plaques may be slowed by statins. (orig.)

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

    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.

  11. Eligibility for Statin Treatment in Korean Subjects with Reduced Renal Function: An Observational Study

    Byung Sub Moon

    2016-09-01

    Full Text Available BackgroundThe purpose of this study was to investigate the relationship between statin eligibility and the degree of renal dysfunction using the Adult Treatment Panel (ATP III and the American College of Cardiology (ACC/American Heart Association (AHA guidelines in Korean adults.MethodsRenal function was assessed in 18,746 participants of the Kangbuk Samsung Health Study from January 2011 to December 2012. Subjects were divided into three groups according to estimated glomerular filtration rate (eGFR: stage 1, eGFR ≥90 mL/min/1.73 m2; stage 2, eGFR 60 to 89 mL/min/1.73 m2; and stages 3 to 5, eGFR <60 mL/min/1.73 m2. Statin eligibility in these groups was determined using the ATP III and ACC/AHA guidelines, and the risk for 10-year atherosclerotic cardiovascular disease (ASCVD was calculated using the Framingham Risk Score (FRS and Pooled Cohort Equation (PCE.ResultsThere were 3,546 (18.9% and 4,048 (21.5% statin-eligible subjects according to ATP III and ACC/AHA guidelines, respectively. The proportion of statin-eligible subjects increased as renal function deteriorated. Statin eligibility by the ACC/AHA guidelines showed better agreement with the Kidney Disease Improving Global Outcomes (KDIGO recommendations compared to the ATP III guidelines in subjects with stage 3 to 5 chronic kidney disease (CKD (κ value, 0.689 vs. 0.531. When the 10-year ASCVD risk was assessed using the FRS and PCE, the mean risk calculated by both equations significantly increased as renal function declined.ConclusionsThe proportion of statin-eligible subjects significantly increased according to worsening renal function in this Korean cohort. ACC/AHA guideline showed better agreement for statin eligibility with that recommended by KDIGO guideline compared to ATP III in subjects with CKD.

  12. Statin Treatment in Hypercholesterolemic Men Does Not Attenuate Angiotensin II-Induced Venoconstriction

    Schindler, Christoph; Guenther, Kristina; Hermann, Cosima; Ferrario, Carlos M.; Schroeder, Christoph; Haufe, Sven

    2014-01-01

    Experimental studies suggested that statins attenuate vascular AT1 receptor responsiveness. Moreover, the augmented excessive pressor response to systemic angiotensin II infusions in hypercholesterolemic patients was normalized with statin treatment. In 12 hypercholesterolemic patients, we tested the hypothesis that statin treatment attenuates angiotensin II-mediated vasoconstriction in hand veins assessed by a linear variable differential transducer. Subjects ingested daily doses of either atorvastatin (40 mg) or positive control irbesartan (150 mg) for 30 days in a randomized and cross-over fashion. Ang II–induced venoconstriction at minute 4 averaged 59%±10% before and 28%±9% after irbesartan (mean ± SEM; Pblood pressure buffering reflexes. Trial Registration ClinicalTrials.gov NCT00154024 PMID:25264877

  13. Comparing Guidelines for Statin Treatment in Canada and the United States.

    Hennessy, Deirdre A; Bushnik, Tracey; Manuel, Douglas G; Anderson, Todd J

    2015-07-14

    New guidelines for cardiovascular disease risk assessment and statin eligibility have recently been published in the United States by the American College of Cardiology and the American Heart Association (ACC-AHA). It is unknown how these guidelines compare with the Canadian Cardiovascular Society (CCS) recommendations. Using data from the Canadian Health Measures Survey 2007-2011, we estimated the cardiovascular disease risk and proportion of the Canadian population, aged 40 to 75 years without cardiovascular disease, who would theoretically be eligible for statin treatment under both the CCS and ACC-AHA guidelines. The survey sample used (n=1975) represented 13.1 million community dwelling Canadians between the ages of 40 and 75 years. In comparing the CVD risk assessment methods, we found that calculated CVD risk was higher based on the CCS guidelines compared with the ACC-AHA guidelines. Despite this, a similar proportion and number of Canadians would be eligible for statin treatment under the 2 sets of recommendations. Some discordance in recommendations was found within subgroups of the population, with the CCS guidelines recommending more treatment for individuals who are younger, with a family history of CVD, or with chronic kidney disease. The ACC-AHA recommend more treatment for people who are older (age 60+ years). These results likely overestimate the treatment rate under both guidelines because, in primary prevention, a clinician-patient discussion must occur before treatment and determines uptake. Implementing the ACC-AHA lipid treatment guidelines in Canada would not result in an increase in individuals eligible for statin treatment. In fact, the proportion of the population recommended for statin treatment would decrease slightly and be targeted at different subgroups of the population. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  14. Statin Treatment and Clinical Outcomes of Heart Failure Among Africans: An Inverse Probability Treatment Weighted Analysis.

    Bonsu, Kwadwo Osei; Owusu, Isaac Kofi; Buabeng, Kwame Ohene; Reidpath, Daniel D; Kadirvelu, Amudha

    2017-04-01

    Randomized control trials of statins have not demonstrated significant benefits in outcomes of heart failure (HF). However, randomized control trials may not always be generalizable. The aim was to determine whether statin and statin type-lipophilic or -hydrophilic improve long-term outcomes in Africans with HF. This was a retrospective longitudinal study of HF patients aged ≥18 years hospitalized at a tertiary healthcare center between January 1, 2009 and December 31, 2013 in Ghana. Patients were eligible if they were discharged from first admission for HF (index admission) and followed up to time of all-cause, cardiovascular, and HF mortality or end of study. Multivariable time-dependent Cox model and inverse-probability-of-treatment weighting of marginal structural model were used to estimate associations between statin treatment and outcomes. Adjusted hazard ratios were also estimated for lipophilic and hydrophilic statin compared with no statin use. The study included 1488 patients (mean age 60.3±14.2 years) with 9306 person-years of observation. Using the time-dependent Cox model, the 5-year adjusted hazard ratios with 95% CI for statin treatment on all-cause, cardiovascular, and HF mortality were 0.68 (0.55-0.83), 0.67 (0.54-0.82), and 0.63 (0.51-0.79), respectively. Use of inverse-probability-of-treatment weighting resulted in estimates of 0.79 (0.65-0.96), 0.77 (0.63-0.96), and 0.77 (0.61-0.95) for statin treatment on all-cause, cardiovascular, and HF mortality, respectively, compared with no statin use. Among Africans with HF, statin treatment was associated with significant reduction in mortality. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

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

    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,...

  16. [C-reactive protein changes with antihypertensive and statin treatment].

    Rodilla, Enrique; Gómez-Belda, Ana; Costa, José A; Aragó, Miriam; Miralles, Amparo; González, Carmen; Pascual, José M

    2005-10-29

    The aim of this study was to evaluate the modifications of high sensitivity C-reactive protein (CRP) with antihypertensive and statin treatment in a hypertensive population with a wide range of coronary risks (CR). Retrospective follow-up study in 665 hypertensive patients: 556 (52% male) without dyslipidemia and CR (Framingham at 10 years) of 8.3 (7.6) as a control group (C) and 109 (61% male) with dyslipidemia and CR of 13.1 (8.8) who were treated with statins (T). Statins treatment was established according to NCEP-ATP-III. In both groups, the antihypertensive treatment was optimized in order to achieve blood pressure (BP) control (< 140/90 mmHg). A lipid profile and high sensitivity CRP (analyzed by nephelometry) was performed at the beginning and at the end of follow up [14.3 (3.6) months]. CRP levels were reduced in the T group -0.17 (0.2) mg/L vs. 0.14 (0.09) mg/L (p = 0.003, Mann-Whitney) in C. The lessening of CRP was not related to the reduction of lipids levels: total cholesterol (r = 0.06; p = 0.49), LDL-C (r = 0.11; p = 0.24), triglycerides (r = -0.02; p = 0.81) (Spearman), or to the reduction of systolic BP (r = -0.07; p = 0.44) and diastolic BP (r = -0.121; p = 0.21). The T group was treated with more antihypertensive drugs than C (2.2 [2.3] vs. 2.5 [1.2]; p = 0.02). Patients treated with ECA inhibitors or angiotensin II antagonist showed a tendency to decreasing the CRP levels more (p = 0.08). In hypertensive populations, statins induce a reduction of CRP levels. The reduction is not related to the lowering of lipids levels or BP values. The effect of statins on the reduction of CRP in hypertensive patients is not related to the lowering of lipids or BP.

  17. Statins and daptomycin: safety assessment of concurrent use and evaluation of drug interaction liability.

    Golightly, Larry K; Barber, Gerard R; Barron, Michelle A; Page, Robert L

    2013-01-01

    Acute muscle injury and potentially fatal rhabdomyolysis may occur with use of statins and certain interacting medications. This investigation assessed risk for myopathy in patients receiving treatment with a statin in combination with daptomycin, a medication also associated with muscle injury. Patients hospitalized from July 1, 2005, through June 30, 2010, who received simvastatin or rosuvastatin concurrently with daptomycin were identified and their medical records were examined. Patients were judged to have treatment-related muscle injury if their records contained evidence of myalgia with or without weakness and secondarily impaired mobility together with elevated creatine kinase (CK) levels. These assessments were compared with similar data from hospitalized patients who received a statin alone. A total of 52 patients received 66 courses of concurrent treatment with simvastatin or rosuvastatin and daptomycin. Of these, no patient (0%) met evidentiary requirements for diagnosis of myopathy or related complications. No patient (0%) developed muscle pain or discomfort and none developed markedly elevated CK levels. The incidence of asymptomatic elevations of CK in these simvastatin or rosuvastatin plus daptomycin recipients (9%) was statistically indistinguishable from the incidence of CK elevations found in a cohort of 105 inpatients who received simvastatin or rosuvastatin alone (21%; p=0.135). In patients receiving treatment with simvastatin or rosuvastatin and daptomycin, no symptoms or objective evidence of muscle injury attributable to a drug interaction were identified. These findings are consistent with data indicating that the myopathic effects of statins and daptomycin are incited by disparate and perhaps unique pharmacological mechanisms. Risk of muscle injury therefore appears to be no greater when a statin is administered with daptomycin than when either medication is used alone.

  18. Statin treatment and risk of recurrent venous thromboembolism

    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 ...

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

    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

  20. Primary Prevention With Statins

    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...

  1. Do different methods of modeling statin treatment effectiveness influence the optimal decision?

    B.J.H. van Kempen (Bob); B.S. Ferket (Bart); A. Hofman (Albert); S. Spronk (Sandra); E.W. Steyerberg (Ewout); M.G.M. Hunink (Myriam)

    2012-01-01

    textabstractPurpose. Modeling studies that evaluate statin treatment for the prevention of cardiovascular disease (CVD) use different methods to model the effect of statins. The aim of this study was to evaluate the impact of using different modeling methods on the optimal decision found in such

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

    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

  3. Statins and PPARα agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    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

  4. Statins and PPAR{alpha} agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment

    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.

  5. Pleiotropic effects of statins on the treatment of chronic periodontitis--a systematic review.

    Estanislau, Ilanna Mara Gomes; Terceiro, Icrólio Ribeiro Colares; Lisboa, Mario Roberto Pontes; Teles, Patrícia de Barros; Carvalho, Rosimary de Sousa; Martins, Ricardo Souza; Moreira, Maria Mônica Studart Mendes

    2015-06-01

    Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are an important group of hypolipidaemic drugs, widely used in the treatment of hypercholesterolaemia and cardiovascular disease. Some studies have shown that statins are able to modulate inflammation and alveolar bone loss. In order to evaluate whether statins could influence periodontal treatment, improving the clinical and radiographic parameters in chronic periodontitis, a systematic review was conducted in the databases PUBMED and BIREME, searching for articles in English and Portuguese, published between the years 2004 and 2014, using the combined keywords statin, periodontal disease, periodontitis and alveolar bone. Studies regarding the treatment of chronic periodontitis in humans, blind or double-blind, retrospective cohort or randomized controlled trials that used statins topically or systemically were selected. Statins have important anti-inflammatory and immune effects, reducing levels of C-reactive protein and matrix metalloproteinases and their intermediate products, such as tumour necrosis factor-α, and are also able to inhibit the adhesion and extravasation of leukocytes, which block the co-stimulation of T cells. Statins reduce bone resorption by inhibiting osteoclast formation and lead to increased apoptosis of these cells. The effect of statins on bone formation is related to the increased gene expression of bone morphogenetic protein in osteoblasts. Although we found biological mechanisms and clinical results that show lower alveolar bone loss and reduction of clinical signs of inflammation, further studies are needed to evaluate the clinical applicability of statins in the routine treatment of chronic periodontitis. © 2014 The British Pharmacological Society.

  6. Treatment of dyslipidemia with statins and physical exercises: recent findings of skeletal muscle responses.

    Bonfim, Mariana Rotta; Oliveira, Acary Souza Bulle; do Amaral, Sandra Lia; Monteiro, Henrique Luiz

    2015-04-01

    Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords "statin" AND "exercise" AND "muscle", restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible.

  7. LIFESTAT - Living with statins: An interdisciplinary project on the use of statins as a cholesterol-lowering treatment and for cardiovascular risk reduction.

    Christensen, Christa Lykke; Wulff Helge, Jørn; Krasnik, Allan; Kriegbaum, Margit; Rasmussen, Lene Juel; Hickson, Ian D; Liisberg, Kasper Bering; Oxlund, Bjarke; Bruun, Birgitte; Lau, Sofie Rosenlund; Olsen, Maria Nathalie Angleys; Andersen, John Sahl; Heltberg, Andreas Søndergaard; Kuhlman, Anja Birk; Morville, Thomas Hoffmann; Dohlmann, Tine Lovsø; Larsen, Steen; Dela, Flemming

    2016-07-01

    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% of the population in the Scandinavian countries are treated with statins in order to maintain good health and to avoid cardiovascular disease by counteracting high blood levels of cholesterol. The potential benefit of treatment with statins should be considered in light of evidence that statin use has prevalent and unintended side effects (e.g. myalgia, and glucose and exercise intolerance). The LIFESTAT project combines invasive human experiments, biomedical analyses, nationwide surveys, epidemiological studies, qualitative interviews, media content analyses, and ethnographic participant observations. 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 the way people manage to live with the risk (personally, socially and technologically). CONCLUSIONS THE ORIGINALITY AND SUCCESS OF LIFESTAT DEPEND ON AND DERIVE FROM ITS INTERDISCIPLINARY APPROACH, IN WHICH THE DISCIPLINES CONVERGE INTO THOROUGH AND HOLISTIC STUDY AND DESCRIBE THE IMPACT OF STATIN USE ON THE EVERYDAY LIFE OF STATIN USERS THIS HAS THE POTENTIAL FOR MUCH GREATER BENEFIT THAN ANY ONE OF THE DISCIPLINES ALONE INTEGRATING TRADITIONAL DISCIPLINES PROVIDES NOVEL PERSPECTIVES ON POTENTIAL CURRENT AND FUTURE SOCIAL, MEDICAL AND PERSONAL BENEFITS OF STATIN USE. © 2016 the Nordic Societies of Public Health.

  8. Statin treatment and functional outcome after ischemic stroke: case-control and meta-analysis.

    Biffi, Alessandro; Devan, William J; Anderson, Christopher D; Cortellini, Lynelle; Furie, Karen L; Rosand, Jonathan; Rost, Natalia S

    2011-05-01

    Multiple studies suggest that statin use before acute ischemic stroke is associated with improved functional outcome. However, available evidence is conflicting, and several published reports are limited by small sample sizes. We therefore investigated the effect of antecedent use of statins on stroke outcome by performing a meta-analysis of all results from published studies as well as our own unpublished data. We performed a systematic literature search and meta-analysis of studies investigating the association between prestroke statin use and clinical outcome and included additional data from 126 prestroke statin users and 767 nonusers enrolled at our institution. A total of 12 studies, comprising 2013 statin users and 9682 nonusers, was meta-analyzed using a random effects model. We also meta-analyzed results for individual Trial of ORG 10172 in Acute Stroke Treatment stroke subtypes to determine whether the effect of statin use differed across subtypes using the Breslow-Day test. Meta-analysis of all available data identified an association between prestroke statin use and improved functional outcome (OR, 1.62; 95% CI, 1.39 to 1.88), but we uncovered evidence of publication bias. The effect of statin use on functional outcome was found to be larger for small vessel strokes compared with other subtypes (Breslow-Day P=0.008). Antecedent use of statins is associated with improved outcome in patients with acute ischemic stroke. This association appears to be stronger in patients with small vessel stroke subtype. However, evidence of publication bias in the existing literature suggests these findings should be interpreted with caution.

  9. The effects of 2 weeks of statin treatment on mitochondrial respiratory capacity in middle-aged males

    Asping, Magnus; Stride, Nis; Sogaard, Ditte

    2017-01-01

    Background Statins are used to lower cholesterol in plasma and are one of the most used drugs in the world. Many statin users experience muscle pain, but the mechanisms are unknown at the moment. Many studies have hypothesized that mitochondrial function could be involved in these side effects. Aim...... treatment. Fasting glucose and insulin as well as VO2max were not changed after treatment. Conclusion Two weeks of statin (S or P) treatment have no major effect on mitochondrial function. The tendency for an increased mitochondrial substrate sensitivity after simvastatin treatment could be an early...... indication of the negative effects linked to statin treatment....

  10. Misperception among physicians and patients regarding the risks and benefits of statin treatment: the potential role of direct-to-consumer advertising.

    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.

  11. Treatment of Dyslipidemia with Statins and Physical Exercises: Recent Findings of Skeletal Muscle Responses

    Mariana Rotta Bonfim

    2015-04-01

    Full Text Available Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords “statin” AND “exercise” AND “muscle”, restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible.

  12. Treatment of Dyslipidemia with Statins and Physical Exercises: Recent Findings of Skeletal Muscle Responses

    Bonfim, Mariana Rotta, E-mail: mrb-unesp@yahoo.com.br [Programa de Pós-Graduação em Ciências da Motricidade, Instituto de Biociências, Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP), Rio Claro, SP (Brazil); Oliveira, Acary Souza Bulle [Setor de Doenças Neuromusculares, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP (Brazil); Amaral, Sandra Lia do; Monteiro, Henrique Luiz [Departamento de Educação Física, Faculdade de Ciências, UNESP, Bauru, SP (Brazil)

    2015-04-15

    Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords “statin” AND “exercise” AND “muscle”, restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible.

  13. Treatment of Dyslipidemia with Statins and Physical Exercises: Recent Findings of Skeletal Muscle Responses

    Bonfim, Mariana Rotta; Oliveira, Acary Souza Bulle; Amaral, Sandra Lia do; Monteiro, Henrique Luiz

    2015-01-01

    Statin treatment in association with physical exercise practice can substantially reduce cardiovascular mortality risk of dyslipidemic individuals, but this practice is associated with myopathic event exacerbation. This study aimed to present the most recent results of specific literature about the effects of statins and its association with physical exercise on skeletal musculature. Thus, a literature review was performed using PubMed and SciELO databases, through the combination of the keywords “statin” AND “exercise” AND “muscle”, restricting the selection to original studies published between January 1990 and November 2013. Sixteen studies evaluating the effects of statins in association with acute or chronic exercises on skeletal muscle were analyzed. Study results indicate that athletes using statins can experience deleterious effects on skeletal muscle, as the exacerbation of skeletal muscle injuries are more frequent with intense training or acute eccentric and strenuous exercises. Moderate physical training, in turn, when associated to statins does not increase creatine kinase levels or pain reports, but improves muscle and metabolic functions as a consequence of training. Therefore, it is suggested that dyslipidemic patients undergoing statin treatment should be exposed to moderate aerobic training in combination to resistance exercises three times a week, and the provision of physical training prior to drug administration is desirable, whenever possible

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

    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.

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

    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.

  16. Initiation and persistence to statin treatment in patients with diabetes receiving glucose-lowering medications 1997- 2006

    Dominguez, H; Schramm, T K; Norgaard, M L

    2009-01-01

    AIMS: Since 2001 guidelines recommend statin treatment in most patients with diabetes. We investigated secular changes in initiation and persistence to statin treatment during a 10-year period in a nationwide cohort of patients initiating glucose-lowering medication (GLM). METHODS: All Danish...... citizens 30 years and older who claimed prescriptions of GLM between 1997 and 2006 were identified from nationwide registers of drug dispensing from pharmacies and hospitalizations, and followed until 2006. Statin treatment was registered if a prescription was claimed during the period. By logistic...... regression we analyzed factors related to initiation and persistence to statin treatment. RESULTS: In total 128,106 patients were included. In 1997 only 7% of the patients receiving GLM claimed statins within the first year after GLM initiation. Despite increasing statin prescriptions the following years...

  17. Treatment patterns and low-density lipoprotein cholesterol (LDL-C) goal attainment among patients receiving high- or moderate-intensity statins.

    Fox, Kathleen M; Tai, Ming-Hui; Kostev, Karel; Hatz, Maximilian; Qian, Yi; Laufs, Ulrich

    2018-05-01

    European clinical guidelines recommend a low-density lipoprotein cholesterol (LDL-C) goal of C goal attainment among atherosclerotic CV disease (ASCVD) patients with various utilization patterns of moderate- or high-intensity statins in routine care. This retrospective cohort study used electronic medical records data from the QuintilesIMS® Disease Analyzer (> 2 million individuals annually) to identify ASCVD (coronary atherosclerosis, stable/unstable angina, myocardial infarction, ischemic stroke, transient ischemic attack, aneurysm, peripheral artery disease) patients on moderate-/high-intensity statin in Germany. Proportion of patients with LDL-C C value for each patient (index) in 2012, 2013, and 2014, while on statin. Treatment patterns were assessed for patients with at least 1 year of post-index follow-up. Results were stratified by year and treatment pattern [no change, switch, dose up-/down-titration, discontinuation (≥ 90 day gap)]. In > 14,000 patients assessed in each year (mean age 71 years, 35% female, 8-12% taking high-intensity statins), approximately 80% had LDL-C ≥ 70 mg/dL. Treatment patterns were assessed for most (88-93%) patients. Approximately 79-81% of patients made no change to statin regimens, 1% switched statins, 14-16% discontinued; 1% of moderate-intensity patients up-titrated, and 3% of all patients down-titrated. LDL-C goal attainment in these treatment pattern groups was 20, 16-24, 17, 11-14, and 17-19%, respectively. Majority of ASCVD patients had LDL-C ≥ 70 mg/dL while on moderate-/high-intensity statins. Despite low LDL-C goal attainment, few patients changed their treatment regimens.

  18. Statin eligibility and cardiovascular risk burden assessed by coronary artery calcium score: comparing the two guidelines in a large Korean cohort.

    Rhee, Eun-Jung; Park, Se Eun; Oh, Hyung Geun; Park, Cheol-Young; Oh, Ki-Won; Park, Sung-Woo; Blankstein, Ron; Plutzky, Jorge; Lee, Won-Young

    2015-05-01

    To investigate the statin eligibility and the predictabilities for cardiovascular disease between AHA/ACC and ATPIII guidelines, comparing those results to concomitant coronary artery calcium scores (CACS) in a large cohort of Korean individuals who met statin-eligibility criteria. Among 19,920 participants in a health screening program, eligibility for statin treatment was assessed by the two guidelines. The presence and extent of coronary artery calcification (CAC) was measured by multi-detector computed tomography and compared among the various groups defined by the two guidelines. Applying the new ACC/AHA guideline to the health screening cohort increased the statin-eligible population from 18.7% (as defined by ATP III) to 21.7%. Statin-eligible subjects as defined only by ACC/AHA guideline manifested a higher proportion of subjects with CAC compared with those meeting only ATP-III criteria even after adjustment for age and sex (47.1 vs. 33.8%, pguideline showed higher odds ratio for the presence of CACS>0 compared with those meeting ATP-III criteria {3.493 (3.245∼3.759) vs. 2.865 (2.653∼3.094)}, which was attenuated after adjusted for age and sex. In this large Korean cohort, more subjects would have qualified for statin initiation under the new ACC/AHA guideline as compared with the proportion recommended for statin treatment by ATP III guideline. Among statin-eligible Korean health screening subjects, the new ACC/AHA guideline identified a greater extent of atherosclerosis as assessed by CACS as compared to ATP III guideline assessment. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Mechanisms and assessment of statin-related muscular adverse effects

    Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

    2014-01-01

    Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

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

    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.

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

    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.

  2. Statin use and 25-hydroxyvitamin D blood level response to vitamin D treatment of older adults

    Objectives: To determine whether statin use alters response of 25-hydroxyvitamin D (25(OH)D) level to vitamin D treatment. Design: Pooled analysis. Setting: Three double-blind randomized controlled trials that tested different doses of vitamin D. Participants: Participants of three trials (N = 646; ...

  3. Statin treatment may lower the risk of postradiation epilepsy in patients with nasopharyngeal carcinoma.

    Rong, Xiaoming; Yin, Jing; Wang, Hongxuan; Zhang, Xiaoni; Peng, Ying

    2017-12-01

    This study aimed to clarify the effect of statins on preventing the risk of postradiation epilepsy. We performed a retrospective analysis of neurological nasopharyngeal carcinoma patients with a history of radiotherapy. Patients with a history of epilepsy before radiation and those who received prophylactically antiepileptic treatment were excluded. The demographic and clinical data of these patients were collected through chart review. We used Kaplan-Meier analysis (log-rank test) to examine the effect of statins on epilepsy-free survival. Cox regression analysis was utilized to identify independent predictive variables. Our study included 532 patients (405 males and 127 females) with a mean follow-up of 28.1 months. During follow-up, 471 (88.5%) patients developed radiation-induced brain necrosis (RN). Within a mean latency of 24.1 months, 88 (16.5%) patients experienced epilepsy, of whom 27 (27 of 88, 30.7%) patients suffered from epilepsy before the diagnosis of RN. Thirty-six (36 of 88, 40.9%) cases of epilepsy occurred after RN onset, and in 22 cases (22 of 88, 25.0%) epilepsy was the first presentation of RN. Three patients suffered from epilepsy but did not have RN. Eighty-eight patients in our cohort were treated with statins because of hyperlipidemia or prevention of cardiocerebrovascular diseases, of whom six (6.8%) developed epilepsy, whereas in those without statin, the epileptic rate was 18.5%. Log-rank test found that there was a significant difference in epilepsy-free survival between patients who used statins and those who did not (p = 0.016). After adjusting for confounding variables, multivariate Cox regression analysis revealed that statin use could still significantly reduce the risk of epilepsy after radiation (hazard ratio = 0.36, 95% confidence interval = 0.15-0.82, p = 0.015). However, for the patients who already suffered from RN, statin treatment did not lower the risk of post-RN epilepsy. Early statin use may reduce the risk of

  4. Predictors and outcomes of increases in creatine phosphokinase concentrations or rhabdomyolysis risk during statin treatment

    van Staa, Tjeerd P; Carr, Daniel F; O’Meara, Helen; McCann, Gerry; Pirmohamed, Munir

    2014-01-01

    Aim The aim was to evaluate clinical risk factors associated with myotoxicity in statin users. Methods This was a cohort study of patients prescribed a statin in UK primary care practices contributing to the Clinical Practice Research Datalink. Outcomes of interest were creatine phosphokinase (CPK) concentrations and clinical records of rhabdomyolysis. Results The cohort comprised 641 703 statin users. Simvastatin was most frequently prescribed (66.3%), followed by atorvastatin (24.4%). CPK was measured in 127 209 patients: 81.4% within normal range and 0.7% above Rhabdomyolysis was recorded in 59 patients. Patients with concomitant prescribing of CYP3A4-interacting drugs had an increased odds ratio (OR) of rhabdomyolysis compared with controls (OR 3.71, 95% CI 1.18, 11.61) and >four times ULN CPK compared with normal CPK (OR 1.28, 95% CI 1.01, 1.60). Rosuvastatin users had higher risk of >four times ULN CPK (OR 1.62, 95% CI 1.22, 2.15) as did patients with larger daily doses of other statin types. A recent clinical record of myalgia was associated with an increased OR of >four times ULN CPK (OR 1.73, 95% CI 1.37, 2.18). In patients who were rechallenged to statins and had repeat CPK measurements after >four times ULN CPK abnormalities, 54.8% of the repeat CPK values were within normal range, 32.1% between one to three times and 13.0% >four times ULN. Conclusions The frequencies of substantive CPK increases and rhabdomyolysis during statin treatment were low, with highest risks seen in those on large daily doses or interacting drugs and on rosuvastatin. CPK measurements appeared to have been done in a haphazard manner and better guidance is needed. PMID:24602118

  5. Viewpoint: Personalizing Statin Therapy

    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.

  6. A statin a day keeps the doctor away: comparative proverb assessment modelling study

    Mizdrak, Anja; Scarborough, Peter

    2013-01-01

    Objective To model the effect on UK vascular mortality of all adults over 50 years old being prescribed either a statin or an apple a day. Design Comparative proverb assessment modelling study. Setting United Kingdom. Population Adults aged over 50 years. Intervention Either a statin a day for people not already taking a statin or an apple a day for everyone, assuming 70% compliance and no change in calorie consumption. The modelling used routinely available UK population datasets; parameters describing the relations between statins, apples, and health were derived from meta-analyses. Main outcome measure Mortality due to vascular disease. Results The estimated annual reduction in deaths from vascular disease of a statin a day, assuming 70% compliance and a reduction in vascular mortality of 12% (95% confidence interval 9% to 16%) per 1.0 mmol/L reduction in low density lipoprotein cholesterol, is 9400 (7000 to 12 500). The equivalent reduction from an apple a day, modelled using the PRIME model (assuming an apple weighs 100 g and that overall calorie consumption remains constant) is 8500 (95% credible interval 6200 to 10 800). Conclusions Both nutritional and pharmaceutical approaches to the prevention of vascular disease may have the potential to reduce UK mortality significantly. With similar reductions in mortality, a 150 year old health promotion message is able to match modern medicine and is likely to have fewer side effects.

  7. Statins and risk of poststroke hemorrhagic complications

    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. Statin Intolerance: the Clinician's Perspective.

    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.

  9. Treatment of statin compounds by advanced oxidation processes: Kinetic considerations and destruction mechanisms

    Razavi, Behnaz; Song, Weihua; Santoke, Hanoz; Cooper, William J.

    2011-03-01

    This study examined the use of advanced oxidation/reduction processes (AO/RPs) for the destruction of cholesterol lowering statin pharmaceuticals. AO/RPs which utilize the oxidizing hydroxyl radical ( rad OH) and reducing aqueous electron (e -aq), to degrade chemical contaminants are alternatives to traditional water treatment methods, and are alternatives as water reuse becomes more generally implemented. Four major statin pharmaceuticals, fluvastatin, lovastatin, pravastatin and simvastatin, were studied, and the absolute bimolecular reaction rate constants with rad OH determined, (6.96±0.16)×10 9, (2.92±0.06)×10 9, (4.16±0.13)×10 9, and (3.13±0.15)×10 9 M -1 s -1, and for e -aq (2.31±0.06)×10 9, (0.45±0.01)×10 9, (1.26±0.01)×10 9, and (0.69±0.02)×10 9 M -1 s -1, respectively. To provide additional information on the radicals formed upon oxidation, transient spectra were measured and the overall reaction efficiency determined. Radical-based destruction mechanisms for destruction of the statins are proposed based on the LC-MS determination of the stable reaction by-products formed using 137Cs γ-irradiation of statin solutions. Knowing the reaction rates, reaction efficiencies and destruction mechanisms of these compounds is essential for the consideration of the use of advanced oxidation/reduction processes for the destruction of statins in aqueous systems.

  10. Treatment of statin compounds by advanced oxidation processes: Kinetic considerations and destruction mechanisms

    Razavi, Behnaz; Song Weihua; Santoke, Hanoz; Cooper, William J.

    2011-01-01

    This study examined the use of advanced oxidation/reduction processes (AO/RPs) for the destruction of cholesterol lowering statin pharmaceuticals. AO/RPs which utilize the oxidizing hydroxyl radical ( · OH) and reducing aqueous electron (e - aq ), to degrade chemical contaminants are alternatives to traditional water treatment methods, and are alternatives as water reuse becomes more generally implemented. Four major statin pharmaceuticals, fluvastatin, lovastatin, pravastatin and simvastatin, were studied, and the absolute bimolecular reaction rate constants with · OH determined, (6.96±0.16)x10 9 , (2.92±0.06)x10 9 , (4.16±0.13)x10 9 , and (3.13±0.15)x10 9 M -1 s -1 , and for e - aq (2.31±0.06)x10 9 , (0.45±0.01)x10 9 , (1.26±0.01)x10 9 , and (0.69±0.02)x10 9 M -1 s -1 , respectively. To provide additional information on the radicals formed upon oxidation, transient spectra were measured and the overall reaction efficiency determined. Radical-based destruction mechanisms for destruction of the statins are proposed based on the LC-MS determination of the stable reaction by-products formed using 137 Cs γ-irradiation of statin solutions. Knowing the reaction rates, reaction efficiencies and destruction mechanisms of these compounds is essential for the consideration of the use of advanced oxidation/reduction processes for the destruction of statins in aqueous systems.

  11. Treatment of statin compounds by advanced oxidation processes: Kinetic considerations and destruction mechanisms

    Razavi, Behnaz, E-mail: brazavi@uci.ed [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Song Weihua, E-mail: wsong@uci.ed [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Santoke, Hanoz, E-mail: hsantoke@uci.ed [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States); Cooper, William J., E-mail: wcooper@uci.ed [Urban Water Research Center, Department of Civil and Environmental Engineering, University of California, Irvine, Irvine, CA 92697-2175 (United States)

    2011-03-15

    This study examined the use of advanced oxidation/reduction processes (AO/RPs) for the destruction of cholesterol lowering statin pharmaceuticals. AO/RPs which utilize the oxidizing hydroxyl radical ({sup {center_dot}O}H) and reducing aqueous electron (e{sup -}{sub aq}), to degrade chemical contaminants are alternatives to traditional water treatment methods, and are alternatives as water reuse becomes more generally implemented. Four major statin pharmaceuticals, fluvastatin, lovastatin, pravastatin and simvastatin, were studied, and the absolute bimolecular reaction rate constants with {sup {center_dot}O}H determined, (6.96{+-}0.16)x10{sup 9}, (2.92{+-}0.06)x10{sup 9}, (4.16{+-}0.13)x10{sup 9}, and (3.13{+-}0.15)x10{sup 9} M{sup -1} s{sup -1}, and for e{sup -}{sub aq} (2.31{+-}0.06)x10{sup 9}, (0.45{+-}0.01)x10{sup 9}, (1.26{+-}0.01)x10{sup 9}, and (0.69{+-}0.02)x10{sup 9} M{sup -1} s{sup -1}, respectively. To provide additional information on the radicals formed upon oxidation, transient spectra were measured and the overall reaction efficiency determined. Radical-based destruction mechanisms for destruction of the statins are proposed based on the LC-MS determination of the stable reaction by-products formed using {sup 137}Cs {gamma}-irradiation of statin solutions. Knowing the reaction rates, reaction efficiencies and destruction mechanisms of these compounds is essential for the consideration of the use of advanced oxidation/reduction processes for the destruction of statins in aqueous systems.

  12. Associations between patients' risk attitude and their adherence to statin treatment

    Barfoed, Benedicte Lind; Paulsen, Maja Skov; Christensen, Palle Mark

    2016-01-01

    BACKGROUND: Poor adherence to medical treatment may have considerable consequences for the patients' health and for healthcare costs to society. The need to understand the determinants for poor adherence has motivated several studies on socio-demographics and comorbidity. Few studies focus...... on the association between risk attitude and adherence. The aim of the present study was to estimate associations between patients' adherence to statin treatment and different dimensions of risk attitude, and to identify subgroups of patients with poor adherence. METHODS: Population-based questionnaire and register......-based study on a sample of 6393 persons of the general. Danish population aged 20-79. Data on risk attitude were based on 4 items uncovering health-related as well as financial dimensions of risk attitude. They were collected through a web-based questionnaire and combined with register data on redeemed statin...

  13. Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial.

    Alejandro Macchia

    Full Text Available The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG among patients with type II diabetes mellitus and no previous cardiovascular events.Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks, assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018. On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716. The effects of treatments on measurements of TG using other agonists were consistent.While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG.ClinicalTrials.gov NCT00793754.

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

    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.

  15. Use of statins in cardiorenal syndrome : possibilities for its treatment and prevention

    A. M. Minasyan

    2014-07-01

    Full Text Available Cardiovascular diseases are the major cause of disease and death not only in the general population, but also in patients with chronic kidney disease. The growing morbidity and mortality from chronic kidney disease and chronic heart failure conduce to an increase in cases of cardiorenal syndrome. Along with angiotensin-converting enzyme inhibitors, β-adrenoblockers, antianemic drugs, and diuretics, statins are appropriate and recommended by a number of trials for the prevention and treatment of the cardiorenal syndrome. Statins are effective in preventing the cardiorenal syndrome in patients at its high risk, improve quality of life and survival; in predialysis patients with chronic kidney disease, they may be secondary prevention of cardiovascular death.

  16. The influence of statin treatment on the inflammatory biomarkers YKL-40 and HsCRP in patients with stable coronary artery disease

    Mygind, Naja Dam; Harutyunyan, Marina J; Mathiasen, Anders Bruun

    2011-01-01

    OBJECTIVE: The inflammatory biomarker YKL-40 is elevated and associated with mortality in patients with stable coronary artery disease (CAD). The aim was to investigate the influence of statin treatment and lipid status on serum YKL-40 and Hs-CRP in patients with stable CAD. DESIGN: Serum YKL-40......, HsCRP, total cholesterol, HDL-c, LDL-c and triglycerides levels were measured in 404 statin treated and in 404 matched non-statin treated patients with stable CAD. RESULTS: YKL-40 was significantly higher in non-statin treated 110 µg/l (median) compared with 65 µg/l in statin treated (p ...

  17. Retrospective observational assessment of statin adherence among subjects patronizing different types of community pharmacies in Canada.

    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

    time period if they met a proxy criterion for availability for observation, defined as the dispensing of any drug at least 1 day after the end date of each period. Pearson chi square tests were used to assess the significance of differences in baseline characteristics and adherence proportions, comparing pharmacy categories. Logistic regression analysis estimated the odds of an adherence level of at least 80% during the individual observation period, adjusting for pharmacy category, sex, age 65 years or older, known low-income drug coverage, number of distinct drug classes filled concurrently during the first year of observation, loyalty to index pharmacy, and length of observation. Using similar methods, we also estimated "pharmacy loyalty" by calculating the proportion of subjects who refilled 75% or more of their statin prescriptions at the pharmacy that dispensed their first statin prescription. From an initial sample of 12,818 subjects who had at least 1 pharmacy claim for a statin in the period from January 1, 2000, through December 31, 2005, 8699 subjects met the inclusion criteria. Subjects were observed for a mean (SD, range) of 3.7 (1.7, 1.0-7.0) years after the index statin prescription. During the first year following the index claim, statin adherence rates were at least 80% for 1799 of 3761 (47.8%) patrons of department-mass merchandise, 1778 of 3235 (55.0%) patrons of chain-franchise, and 921 of 1703 (54.1%) patrons of independent-banner stores (P franchise, and independent banner categories, respectively, had a statin adherence level of at least 80% (P franchise and independent-banner categories were more likely to be adherent to their statin medications during their observation periods than were those in the department-mass merchandise category (adjusted odds ratio [OR] = 1.36, 95% CI = 1.23-1.50, P franchise, and independent-banner categories, respectively (P = 0.006). Controlling for several potential confounders using logistic regression, independent

  18. The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Echo Study: Rationale and Trial Protocol.

    Toyoda, Kazunori; Minematsu, Kazuo; Yasaka, Masahiro; Nagai, Yoji; Hosomi, Naohisa; Origasa, Hideki; Kitagawa, Kazuo; Uchiyama, Shinichiro; Koga, Masatoshi; Matsumoto, Masayasu

    2017-03-01

    The preventive effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) on progression of carotid intima-media complex thickness (IMT) has been shown exclusively in nonstroke Western patients. The Japan Statin Treatment Against Recurrent Stroke (J-STARS) Echo Study aims to determine the effect of pravastatin on carotid IMT in Japanese patients with hyperlipidemia who developed noncardioembolic ischemic stroke. This is a substudy of the J-STARS, a multicenter, randomized, open-label, blinded-end point, parallel-group trial to examine whether pravastatin reduces stroke recurrence in patients with noncardioembolic stroke. The patients are randomized to receive pravastatin (10 mg daily) or not to receive any statins. Carotid ultrasonography is performed by well-trained certified examiners in each participating institute, and the recorded data are measured centrally. The primary outcome is change in the IMT of the distal wall in a consecutive 2-cm section on the central side of the common carotid artery bifurcation over 5 years of observation. The trial may help determine if the usual dose of pravastatin for daily clinical practice in Japan can affect carotid IMT in Japanese patients with noncardioembolic stroke. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. 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

    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

  20. Simultaneous Treatment with Statins and Aspirin Reduces the Risk of Prostate Cancer Detection and Tumorigenic Properties in Prostate Cancer Cell Lines

    Olivan, M.; Rigau, M.; Colás, E.; Garcia, M.; Montes, M.; Sequeiros, T.; Regis, L.; Celma, A.; Planas, J.; Placer, J.; Reventós, J.; de Torres, I.; Doll, A.; Morote, J.

    2015-01-01

    Nowadays prostate cancer is the most common solid tumor in men from industrialized countries and the second leading cause of death. At the ages when PCa is usually diagnosed, mortality related to cardiovascular morbidity is high; therefore, men at risk for PCa frequently receive chronic lipid-lowering and antiplatelet treatment. The aim of this study was to analyze how chronic treatment with statins, aspirin, and their combination influenced the risk of PCa detection. The tumorigenic properties of these treatments were evaluated by proliferation, colony formation, invasion, and migration assays using different PCa cell lines, in order to assess how these treatments act at molecular level. The results showed that a combination of statins and aspirin enhances the effect of individual treatments and seems to reduce the risk of PCa detection (OR: 0.616 (95% CI: 0.467–0.812), P < 0.001). However, if treatments are maintained, aspirin (OR: 1.835 (95% CI: 1.068–3.155), P = 0.028) or the combination of both drugs (OR: 3.059 (95% CI: 1.894–4.939), P < 0.001) represents an increased risk of HGPCa. As observed at clinical level, these beneficial effects in vitro are enhanced when both treatments are administered simultaneously, suggesting that chronic, concomitant treatment with statins and aspirin has a protective effect on PCa incidence. PMID:25649906

  1. Association Between Adherence to Statins, Illness Perception, Treatment Satisfaction, and Quality of Life among Lebanese patients.

    Haddad, Christine; Hallit, Souheil; Salhab, Mohammad; Hajj, Aline; Sarkis, Antoine; Nasser Ayoub, Eliane; Jabbour, Hicham; Rabbaa Khabbaz, Lydia

    2018-01-01

    The main objective of this study was to evaluate treatment adherence to statin and health-related quality of life (QOL) in Lebanese patients with dyslipidemia. Secondary objectives were to examine associations between treatment adherence, QOL, treatment satisfaction, and illness perception. This cross-sectional study, conducted in 20 community pharmacies from all districts of Lebanon between August 2016 and April 2017, enrolled 247 adult patients taking any statin. The mean age of the participants was 52.63 ± 11.92 years (57.5% males); the mean duration of treatment with a statin was 59.72 months. A significant association was found between adherence and marital status ( P salary, the marital status, the educational level, smoking cigarettes or waterpipes, and drinking alcohol were all associated with the Illness Perception Questionnaire scores ( P < 0.0001 for all variables). Secondary level of education (β = 13.43), smoking more than 3 waterpipes per week (β = 14.06), global satisfaction score (β = 0.32), convenience score (β = 0.29), and effectiveness score (β = 0.27) would significantly increase the adherence score. Smoking more than 15 cigarettes per day (β = -11.15) and a divorced status (β = -14.81) would however significantly decrease the adherence score. Significant associations were found between the illness perception score, the QOL domains, and the satisfaction domains ( P < .05 for all variables). This study showed that global satisfaction with treatment, convenience, and effectiveness are important factors that increase treatment adherence. Patient adherence results in patient satisfaction and improved QOL and is an important criterion for achieving desired therapeutic outcomes.

  2. LDL cholesterol goals and cardiovascular risk during statin treatment

    Olsson, Anders G; Lindahl, Christina; Holme, Ingar

    2011-01-01

    We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how...

  3. Associations between patients' risk attitude and their adherence to statin treatment - a population based questionnaire and register study

    Barfoed, Benedicte Marie Lind; Paulsen, Maja Skov; Christensen, Palle Mark

    2016-01-01

    the risk-averse patients, OR 0.80 (95 %-CI 0.68-0.95) and OR 0.83 (95 %-CI 0.71-0.98), respectively. No significant association was found between adherence and financial risk attitude. Further, patients in the youngest age group and patients with no CVD were less adherent to statin treatment. CONCLUSION......: We find some indication that risk attitude is associated with adherence to statin treatment, and that risk-neutral and risk-seeking patients may have poorer adherence than risk-averse patients. This is important for clinicians to consider when discussing optimal treatment decisions...... on the association between risk attitude and adherence. The aim of the present study was to estimate associations between patients' adherence to statin treatment and different dimensions of risk attitude, and to identify subgroups of patients with poor adherence. METHODS: Population-based questionnaire and register...

  4. Muscle-related side-effects of statins: from mechanisms to evidence-based solutions.

    Taylor, Beth A; Thompson, Paul D

    2015-06-01

    This article highlights the recent findings regarding statin-associated muscle side effects, including mechanisms and treatment as well as the need for more comprehensive clinical trials in statin myalgia. Statin myalgia is difficult to diagnose and treat, as major clinical trials have not routinely assessed muscle side-effects, there are few clinically relevant biomarkers and assessment tools for the symptoms, many apparent statin-related muscle symptoms may be nonspecific and related to other drugs or health conditions, and prevalence estimates vary widely. Data thus suggest that only 30-50% of patients with self-reported statin myalgia actually experience muscle pain on statins during blinded, placebo-controlled trials. In addition, evidence to date involving mechanisms underlying statin myalgia and its range of symptoms and presentations supports the hypothesis that there are multiple, interactive and potentially additive mechanisms underlying statin-associated muscle side-effects. There are likely multiple and interactive mechanisms underlying statin myalgia, and recent studies have produced equivocal data regarding prevalence of statin-associated muscle side-effects, contributing factors and effectiveness of common interventions. Therefore, more clinical trials on statin myalgia are critical to the field, as are systematic resources for quantifying, predicting and reporting statin-associated muscle side-effects.

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

    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

  6. Effect of statins on skeletal muscle function.

    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.

  7. A benefit–risk assessment model for statins using multicriteria decision analysis based on a discrete choice experiment in Korean patients

    Byun JH

    2016-06-01

    Full Text Available Ji-Hye Byun,1 Sun-Hong Kwon,1 Ji-Hye Ha,2 Eui-Kyung Lee1 1School of Pharmacy, Sungkyunkwan University, Suwon-si, Gyeonggi-do, 2Ministry of Food and Drug Safety, Cheongju-si, Chungcheongbuk-do, South Korea Purpose: The benefit–risk balance for drugs can alter post approval owing to additional data on efficacy or adverse events. This study developed a quantitative benefit–risk assessment (BRA model for statins using multicriteria decision analysis with discrete choice experiments and compared a recent BRA with that at the time of approval. Patients and methods: Following a systematic review of the literature, the benefit criteria within the statin BRA model were defined as a reduction in the plasma low-density lipoprotein cholesterol level and a reduction in myocardial infarction incidence; the risk criteria were hepatotoxicity (Liv and fatal rhabdomyolysis (Rha. The scores for these criteria were estimated using mixed treatment comparison methods. Weighting was calculated from a discrete choice experiment involving 203 Korean patients. The scores and weights were integrated to produce an overall value representing the benefit–risk balance, and sensitivity analyses were conducted. Results: In this BRA model, low-density lipoprotein (relative importance [RI]: 37.50% was found to be a more important benefit criterion than myocardial infarction (RI: 35.43%, and Liv (RI: 16.28% was a more important risk criterion than Rha (RI: 10.79%. Patients preferred atorvastatin, and the preference ranking of cerivastatin and simvastatin was switched post approval because of the emergence of additional risk information related to cerivastatin. Conclusion: A quantitative statin BRA model confirmed that the preference ranking of statins changed post approval because of the identification of additional benefits or risks. Keywords: multicriteria decision analysis, statin, quantitative benefit–risk assessment, discrete choice experiment

  8. Effects of Statin Treatment on Inflammation and Cardiac Function in Heart Failure: An Adjusted Indirect Comparison Meta-Analysis of Randomized Trials.

    Bonsu, Kwadwo Osei; Reidpath, Daniel Diamond; Kadirvelu, Amudha

    2015-12-01

    Statins are known to prevent heart failure (HF). However, it is unclear whether statins as class or type (lipophilic or hydrophilic) improve outcomes of established HF. The current meta-analysis was performed to compare the treatment effects of lipophilic and hydrophilic statins on inflammation and cardiac function in HF. Outcomes were indicators of cardiac function [changes in left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP)] and inflammation [changes in highly sensitive C-reactive protein (hsCRP) and interluekin-6 (IL-6)]. We conducted a search of PubMed, EMBASE, and the Cochrane databases until December 31, 2014 for randomized control trials (RCTs) of statin versus placebo in patients with HF. RCTs with their respective extracted information were dichotomized into statin type evaluated and analyzed separately. Outcomes were pooled with random effect approach, producing standardized mean differences (SMD) for each statin type. Using these pooled estimates, we performed adjusted indirect comparisons for each outcome. Data from 6214 patients from 19 trials were analyzed. Lipophilic statin was superior to hydrophilic statin treatment regarding follow-up LVEF (SMD, 4.54; 95% CI, 4.16-4.91; P statin produces greater treatment effects on cardiac function and inflammation compared with hydrophilic statin in patients with HF. Until data from adequately powered head-to-head trial of the statin types are available, our meta-analysis brings clinicians and researchers a step closer to the quest on which statin--lipophilic or hydrophilic--is associated with better outcomes in HF. © 2015 John Wiley & Sons Ltd.

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

    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.

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

    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

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

    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

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

    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

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

    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.

  14. Statin-related myotoxicity.

    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.

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

    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

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

    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.

  17. Comprehensive efforts to increase adherence to statin therapy

    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...

  18. Statin-Associated Side Effects.

    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.

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

    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.

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

    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.

  1. Statin treatment and stroke outcome in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

    Goldstein, L.B.; Amarenco, P.; Zivin, J.

    2009-01-01

    BACKGROUND AND PURPOSE: Laboratory experiments suggest statins reduce stroke severity and improve outcomes. The Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial was a placebo-controlled, randomized trial designed to determine whether treatment with atorvastatin reduces...... or 4), moderate (modified Rankin Scale score 3 or 2), and mild (modified Rankin Scale score 1 or 0) outcome ischemic strokes and transient ischemic attacks and an increase in the proportion of event-free subjects randomized to atorvastatin (P

  2. The Impact of Exercise on Statin-Associated Skeletal Muscle Myopathy

    Chung, Hae R.; Vakil, Mayand; Munroe, Michael; Parikh, Alay; Meador, Benjamin M.; Wu, Pei T.; Jeong, Jin H.; Woods, Jeffrey A.; Wilund, Kenneth R.; Boppart, Marni D.

    2016-01-01

    HMG-CoA reductase inhibitors (statins) are the most effective pharmacological means of reducing cardiovascular disease risk. The most common side effect of statin use is skeletal muscle myopathy, which may be exacerbated by exercise. Hypercholesterolemia and training status are factors that are rarely considered in the progression of myopathy. The purpose of this study was to determine the extent to which acute and chronic exercise can influence statin-induced myopathy in hypercholesterolemic (ApoE-/-) mice. Mice either received daily injections of saline or simvastatin (20 mg/kg) while: 1) remaining sedentary (Sed), 2) engaging in daily exercise for two weeks (novel, Nov), or 3) engaging in daily exercise for two weeks after a brief period of training (accustomed, Acct) (2x3 design, n = 60). Cholesterol, activity, strength, and indices of myofiber damage and atrophy were assessed. Running wheel activity declined in both exercise groups receiving statins (statin x time interaction, pstatin treatment (statin main effect, pstatin x exercise interaction, pstatin treatment. Exercise (Acct and Nov) increased atrogin-1 mRNA in combination with statin treatment, yet enhanced fiber damage or atrophy was not observed. The results from this study suggest that exercise (Nov, Acct) does not exacerbate statin-induced myopathy in ApoE-/- mice, yet statin treatment reduces activity in a manner that prevents muscle from mounting a beneficial adaptive response to training. PMID:27936249

  3. Human skeletal muscle drug transporters determine local exposure and toxicity of statins.

    Knauer, Michael J; Urquhart, Bradley L; Meyer zu Schwabedissen, Henriette E; Schwarz, Ute I; Lemke, Christopher J; Leake, Brenda F; Kim, Richard B; Tirona, Rommel G

    2010-02-05

    The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, or statins, are important drugs used in the treatment and prevention of cardiovascular disease. Although statins are well tolerated, many patients develop myopathy manifesting as muscle aches and pain. Rhabdomyolysis is a rare but severe toxicity of statins. Interindividual differences in the activities of hepatic membrane drug transporters and metabolic enzymes are known to influence statin plasma pharmacokinetics and risk for myopathy. Interestingly, little is known regarding the molecular determinants of statin distribution into skeletal muscle and its relevance to toxicity. We sought to identify statin transporters in human skeletal muscle and determine their impact on statin toxicity in vitro. We demonstrate that the uptake transporter OATP2B1 (human organic anion transporting polypeptide 2B1) and the efflux transporters, multidrug resistance-associated protein (MRP)1, MRP4, and MRP5 are expressed on the sarcolemmal membrane of human skeletal muscle fibers and that atorvastatin and rosuvastatin are substrates of these transporters when assessed using a heterologous expression system. In an in vitro model of differentiated, primary human skeletal muscle myoblast cells, we demonstrate basal membrane expression and drug efflux activity of MRP1, which contributes to reducing intracellular statin accumulation. Furthermore, we show that expression of human OATP2B1 in human skeletal muscle myoblast cells by adenoviral vectors increases intracellular accumulation and toxicity of statins and such effects were abrogated when cells overexpressed MRP1. These results identify key membrane transporters as modulators of skeletal muscle statin exposure and toxicity.

  4. Statin treatment prevents increased cardiovascular and all-cause mortality associated with clarithromycin in patients with stable coronary heart disease

    Jensen, Gorm B; Hilden, Jørgen; Als-Nielsen, Bodil

    2010-01-01

    In the CLARICOR trial, significantly increased cardiovascular (CV) and all-cause mortality in stable patients with coronary heart disease were observed after a short course of clarithromycin. We report on the impact of statin treatment at entry on the CV and all-cause mortality. The multicenter...... CLARICOR trial randomized patients to oral clarithromycin (500 mg daily; n = 2172) versus matching placebo (daily; n = 2201) for 2 weeks. Patients were followed through public databases. In the 41% patients on statin treatment at entry, no significant effect of clarithromycin was observed on CV (hazard...... ratio [HR], 0.68, 95% confidence interval [CI], 0.38-1.22; P = 0.20) or all-cause mortality (HR, 1.08; 95% CI, 0.71-1.65; P = 0.72) at 2.6-year follow up. In the patients not on statin treatment at entry, clarithromycin was associated with a significant increase in CV (HR, 1.90; 95% CI, 1.34-2.67; P = 0...

  5. Statins and breast cancer prognosis

    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...

  6. 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

    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...

  7. Contour plot assessment of existing meta-analyses confirms robust association of statin use and acute kidney injury risk.

    Chevance, Aurélie; Schuster, Tibor; Steele, Russell; Ternès, Nils; Platt, Robert W

    2015-10-01

    Robustness of an existing meta-analysis can justify decisions on whether to conduct an additional study addressing the same research question. We illustrate the graphical assessment of the potential impact of an additional study on an existing meta-analysis using published data on statin use and the risk of acute kidney injury. A previously proposed graphical augmentation approach is used to assess the sensitivity of the current test and heterogeneity statistics extracted from existing meta-analysis data. In addition, we extended the graphical augmentation approach to assess potential changes in the pooled effect estimate after updating a current meta-analysis and applied the three graphical contour definitions to data from meta-analyses on statin use and acute kidney injury risk. In the considered example data, the pooled effect estimates and heterogeneity indices demonstrated to be considerably robust to the addition of a future study. Supportingly, for some previously inconclusive meta-analyses, a study update might yield statistically significant kidney injury risk increase associated with higher statin exposure. The illustrated contour approach should become a standard tool for the assessment of the robustness of meta-analyses. It can guide decisions on whether to conduct additional studies addressing a relevant research question. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. The Effect of Statins on Skeletal Muscle Function

    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

  9. Regulation of apoptosis in human melanoma and neuroblastoma cells by statins, sodium arsenite and TRAIL: a role of combined treatment versus monotherapy

    Ivanov, Vladimir N.; Hei, Tom K.

    2015-01-01

    Treatment of melanoma cells by sodium arsenite or statins (simvastatin and lovastatin) dramatically modified activities of the main cell signaling pathways resulting in the induction of heme oxygenase-1 (HO-1) and in a downregulation of cyclooxygenase-2 (COX-2) protein levels. Through heme degradation and the production of carbon monoxide and biliverdin, HO-1 plays a protective role in different scenario of oxidative stress followed by mitochondrial apoptosis. Both sodium arsenite and statins could be efficient inducers of apoptosis in some melanoma cell lines, but often exhibited only modest proapoptotic activity in others, due to numerous protective mechanisms. We demonstrated in the present study that treatment by sodium arsenite or statins with an additional inhibition of HO-1 expression (or activation) caused a substantial upregulation of apoptosis in melanoma cells. Sodium arsenite- or statin-induced apoptosis was independent of BRAF status (wild type versus V600E) in melanoma lines. Monotreatment required high doses of statins (20–40 μM) for effective induction of apoptosis. As an alternative approach, pretreatment of melanoma cells with statin at decreased doses (5–20 μM) dramatically enhanced TRAIL-induced apoptosis, due to suppression of the NF-κB and STAT3-transcriptional targets (including COX-2) and downregulation of cFLIP-L (a caspase-8 inhibitor) protein levels. Furthermore, combined treatment with sodium arsenite and TRAIL or simvastatin and TRAIL efficiently induced apoptotic commitment in human neuroblastoma cells. In summary, our findings on enhancing effects of combined treatment of cancer cells using statin and TRAIL provide the rationale for further preclinical evaluation. PMID:21910007

  10. Implications of lower risk thresholds for statin treatment in primary prevention: analysis of CPRD and simulation modelling of annual cholesterol monitoring.

    McFadden, Emily; Stevens, Richard; Glasziou, Paul; Perera, Rafael

    2015-01-01

    To estimate numbers affected by a recent change in UK guidelines for statin use in primary prevention of cardiovascular disease. We modelled cholesterol ratio over time using a sample of 45,151 men (≥40years) and 36,168 women (≥55years) in 2006, without statin treatment or previous cardiovascular disease, from the Clinical Practice Research Datalink. Using simulation methods, we estimated numbers indicated for new statin treatment, if cholesterol was measured annually and used in the QRISK2 CVD risk calculator, using the previous 20% and newly recommended 10% thresholds. We estimate that 58% of men and 55% of women would be indicated for treatment by five years and 71% of men and 73% of women by ten years using the 20% threshold. Using the proposed threshold of 10%, 84% of men and 90% of women would be indicated for treatment by 5years and 92% of men and 98% of women by ten years. The proposed change of risk threshold from 20% to 10% would result in the substantial majority of those recommended for cholesterol testing being indicated for statin treatment. Implications depend on the value of statins in those at low to medium risk, and whether there are harms. Copyright © 2014. Published by Elsevier Inc.

  11. Pleiotropic effects of statins

    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.

  12. [Statins and muscle pain].

    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.

  13. Immune-mediated statin myopathy.

    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.

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

    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

  15. Statin Resistance and Export

    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...

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

    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.

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

    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.

  18. Significant improvement in statin adherence and cholesterol levels after acute myocardial infarction

    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....

  19. Estatinas, uso racional en el tratamiento de la dislipoproteinemia Statins related to a rational use in treatment of dyslipoproteinemia

    José Illnait Ferrer

    2009-09-01

    Full Text Available Las estatinas constituyen un grupo de medicamentos eficaces en el control de la hipercolesterolemia. La mayor parte de la información sobre las estatinas está dedicada a resaltar sus virtudes. El propósito del artículo es llamar la atención sobre aspectos no tan difundidos, o al menos, no suficientemente tomados en cuenta. A las estatinas se asocian algunos efectos indeseables que deben ser tomados en consideración para lograr un mejor tratmiento de los pacientes dislipoproteinémicos. Las interacciones medicamentosas, las altas dosis, la edad, el sexo, y otras enfermedades concomitantes como la diabetes, pueden condicionar efectos colaterales indeseables, como los trastornos del sistema nervioso central, la opacidad del cristalino o la elevación de las transaminasas, entre otros, que pueden afectar notablemente la calidad de vida de los pacientes. La rabdomiolisis es uno de los efectos colaterales adversos que más debe tomarse en consideración.Statins are a group of effective drugs in control of hypercholesterolemia. Most of information on statins is devoted to emphasize its virtues. The aim of present paper is to attract the attention on features not so known or at least, non enough took account. Statins have some associated undesirable effects that must to be considered to achieve a better treatment of patients presenting with dyslipoproteinemia. Drug interactions, high doses, age, sex, and other concomitant diseases, e.g. diabetes, may cause undesirable collateral effects, e.g. central nervous system disorders, crystalline lens, or raise of transaminases, among others, that may to affect notably the patients' quality of life. The rabdomyolisis is one of the adverse collateral effects to take into account.

  20. Statin Treatment Is Associated with Reduction in Serum Levels of Receptor Activator of NF-κB Ligand and Neutrophil Activation in Patients with Severe Carotid Stenosis

    Sébastien Lenglet

    2014-01-01

    Full Text Available Systemic and intraplaque biomarkers have been widely investigated in clinical cohorts as promising surrogate parameters of cardiovascular vulnerability. In this pilot study, we investigated if systemic and intraplaque levels of calcification biomarkers were affected by treatment with a statin in a cohort of patients with severe carotid stenosis and being asymptomatic for ischemic stroke. Patients on statin therapy had reduced serum osteopontin (OPN, RANKL/osteoprotegerin (OPG ratio, and MMP-9/pro-MMP-9 activity as compared to untreated patients. Statin-treated patients exhibited increased levels of collagen and reduced neutrophil infiltration in downstream portions of carotid plaques as compared to untreated controls. In upstream plaque portions, OPG content was increased in statin-treated patients as compared to controls. Other histological parameters (such as lipid, macrophage, smooth muscle cell, and MMP-9 content as well as RANKL, RANK, and OPG mRNA levels did not differ between the two patient groups. Serum RANKL/OPG ratio positively correlated with serum levels of neutrophilic products, intraplaque neutrophil, and MMP-9 content within downstream portions of carotid plaques. In conclusion, statin treatment was associated with improvement in serum RANKL levels and reduced neutrophil activity both systemically and in atherosclerotic plaques.

  1. The DYSlipidemia International Study (DYSIS-Egypt: A report on the prevalence of lipid abnormalities in Egyptian patients on chronic statin treatment

    Adel El Etriby

    2013-09-01

    Conclusions: Despite chronic statin treatment, two-thirds of patients in the DYSIS-Egypt study had elevated LDL–C levels. A dual strategy, comprising modification of lifestyle factors together with novel treatment options, appears to be necessary to combat the rise in cardiovascular-related morbidity and mortality.

  2. Statins: Do They Cause ALS?

    ... 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. Uremic Toxins Enhance Statin-Induced Cytotoxicity in Differentiated Human Rhabdomyosarcoma Cells

    Hitoshi Uchiyama

    2014-09-01

    Full Text Available The risk of myopathy and rhabdomyolysis is considerably increased in statin users with end-stage renal failure (ESRF. Uremic toxins, which accumulate in patients with ESRF, exert cytotoxic effects that are mediated by various mechanisms. Therefore, accumulation of uremic toxins might increase statin-induced cytotoxicity. The purpose of this study was to determine the effect of four uremic toxins—hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionate, indole-3-acetic acid, and 3-indoxyl sulfate—on statin-induced myopathy. Differentiated rhabdomyosarcoma cells were pre-treated with the uremic toxins for seven days, and then the cells were treated with pravastatin or simvastatin. Cell viability and apoptosis were assessed by viability assays and flow cytometry. Pre-treatment with uremic toxins increased statin- but not cisplatin-induced cytotoxicity (p < 0.05 vs. untreated. In addition, the pre-treatment increased statin-induced apoptosis, which is one of the cytotoxic factors (p < 0.05 vs. untreated. However, mevalonate, farnesol, and geranylgeraniol reversed the effects of uremic toxins and lowered statin-induced cytotoxicity (p < 0.05 vs. untreated. These results demonstrate that uremic toxins enhance statin-induced apoptosis and cytotoxicity. The mechanism underlying this effect might be associated with small G-protein geranylgeranylation. In conclusion, the increased severity of statin-induced rhabdomyolysis in patients with ESRF is likely due to the accumulation of uremic toxins.

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

    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...

  5. Postdiagnosis statin use and mortality in danish patients with prostate cancer

    Larsen, Signe Benzon; Dehlendorff, Christian; Skriver, Charlotte

    2017-01-01

    Purpose Increasing evidence indicates that statin use may reduce mortality from prostate cancer. In this work, we examined whether postdiagnosis statin use was associated with reduced cancer-specific mortality or all-cause mortality among patients with prostate cancer in Denmark. Material...... and Methods From nationwide Danish registries, we identified all patients with incident prostate adenocarcinoma from 1998 to 2011 and retrieved data on tumor and patient characteristics, drug use, and primary treatment. We defined postdiagnosis use (two or more prescriptions) of statins as a time......-varying covariate with 1-year lag. Cox proportional hazards regression models used to compute hazard ratios (HRs) for prostate cancer-specific mortality and all-cause mortality through 2013 associated with postdiagnosis statin use. In secondary and sensitivity analyses, we assessed statin use within exposure...

  6. The effect of statin treatment on the prevention of stent mediated flow limited edge dissections during PCI in patients with stable angina.

    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.

  7. Direct to consumer Internet advertising of statins: an assessment of safety.

    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.

  8. Statins for aortic valve stenosis

    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

  9. Statins for aortic valve stenosis.

    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

  10. The use of statins in primary prevention

    Stürzlinger, Heidi

    2006-04-01

    Full Text Available Background: The use of statins in secondary prevention of cardiovascular events is well established. However, there is ongoing discussion about the use of statins in the context of primary prevention. Moreover statins - besides cholesterol-lowering effects - are assumed to have pleiotropic effects. Positive impacts on diseases like stroke, Alzheimer's disease or osteoporosis are discussed but still have to be proven. Objectives: The aim of this report is first to investigate the efficacy and effectiveness of statins in primary prevention of cardiovascular and non-cardiovascular events and second to examine the economic implications for Germany - particularly in comparison to existing prevention programs. Finally ethical questions are considered. Methods: A systematic literature search was performed for the period between 1998 and 2004 which yielded 3704 abstracts. Overall 43 articles were included for assessment and 167 for background information, according to predefined selection criteria. Results: Most studies within the context of primary prevention describe significant risk reductions with regard to cardiovascular events; yet no significant results according to the reduction of the overall mortality rate can be seen. With respect to stroke, osteoporosis and Alzheimer's disease results are inconsistent. Regarding cost-effectiveness of primary prevention with statins results turn out to be inconsistent as well or even negative for populations with low to moderate risk. For groups with high cardiovascular risk the intervention is mostly assessed to be cost-effective. No cost-effectiveness study for Germany was found. According to a rough estimate of future expenses statin drug expenses of the German legal health insurance might increase at least by 50% in the case of an enlargement of the group of recipients. Discussion: To thoroughly estimate the cost-effectiveness of the use of statins in primary prevention in Germany a model calculation

  11. Use of low density lipoprotein particle number levels as an aid in statin treatment decisions for intermediate risk patients: a cost-effectiveness analysis.

    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

  12. Antihyperlipidemic Medication Treatment Patterns and Statin Adherence Among Patients with ASCVD in a Managed Care Plan After Release of the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol.

    Bellows, Brandon K; Olsen, Cody J; Voelker, Jennifer; Wander, Curtis

    2016-08-01

    The American College of Cardiology (ACC) and American Heart Association (AHA) released a new blood cholesterol treatment guideline in November 2013. It is unknown how the new recommendations have affected cholesterol medication use and adherence in a commercial health plan. To evaluate the effect of the 2013 guideline release on antihyperlipidemic treatment patterns and statin adherence in patients with atherosclerotic cardiovascular disease (ASCVD) compared with a historical control group. This study was a historical cohort analysis of adult patients (aged 21-75 years) with clinical ASCVD enrolled in a SelectHealth commercial health plan. Patients were included in the guideline implementation cohort if they had a medical claim with an ICD-9-CM diagnosis of ASCVD in the year before the November 2013 ACC/AHA guideline release. The index date was defined as the first outpatient medical claim with an ICD-9-CM for ASCVD in the first 6 months after the guideline was released. Patients were required to have continuous enrollment for ≥ 1 year before and after the index date. These same criteria were applied to patients exactly 4 years earlier to identify a historical control group. Patients meeting these criteria formed the antihyperlipidemic treatment patterns cohort. Of these, patients who also had ≥1 pharmacy claim for a statin in the 1-year pre- and post-index periods were included in the statin adherence cohort. Antihyperlipidemic treatment patterns were assessed using pharmacy claims for antihyperlipidemic medications in the 1-year pre- and post-index periods. Antihyperlipidemic medication claims were classified as a nonstatin cholesterol medication, low-intensity statin, moderate-intensity statin, or high-intensity statin. To address differences in pre-index antihyperlipidemic medications between the guideline implementation and historical control groups, patients were randomly matched 1:1 based on pre-index classification in a post hoc analysis. Post

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

    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

  14. Efficacy of standard and intensive statin treatment for the secondary prevention of cardiovascular and cerebrovascular events in diabetes patients : A meta-analysis

    De Vries, Folgerdiena M.; Kolthof, Johan; Postma, Maarten J.; Denig, Petra; Hak, Eelko

    2014-01-01

    Aims: To estimate the efficacy of standard and intensive statin treatment in the secondary prevention of major cardiovascular and cerebrovascular events in diabetes patients. Methods: A systematic search was conducted in Medline over the years 1990 to September 2013. Randomized, double-blind,

  15. Pattern of statin use in southern Italian primary care: Can prescription databases be used for monitoring long-term adherence to the treatment?

    C. Ferrajolo (Carmen); V. Arcoraci (Vincenzo); M.G. Sullo (Maria Giuseppa); C. Rafaniello (Concetta); L. Sportiello (Liberata); R. Ferrara (Rosarita); A. Cannata (Angelo); C. Pagliaro (Claudia); M.G. Tari (Michele Giuseppe); A.P. Caputi (Achille); F. Rossi (Francesco); G. Trifirò (Gianluca); A. Capuano (Annalisa)

    2014-01-01

    textabstractObjectives: We sought to evaluate the prescribing pattern of statins according to national and regional health policy interventions and to assess specifically the adherence to the therapy in outpatient setting in Southern Italy. Methods: A population-based study was performed on persons

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

    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.

  17. Statins-More Than Just Plaque Stabilisation

    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.

  18. Cholesterol suppresses antimicrobial effect of statins

    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.

  19. Review Article Therapeutic Potential of Statins in Age-related ...

    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-.

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

    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

    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. 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 by a computer-generated sequence to receive rosuvastatin 20 mg per day or placebo, with participants and adjudicators masked to treatment assignment. In the present analysis, we divided the participants into quartiles of HDL-cholesterol or apolipoprotein A1 and sought evidence of association between 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. For 17,802 patients in the JUPITER trial, rosuvastatin 20 mg per day reduced the incidence of the primary endpoint by 44% (p<0.0001). In 8901 (50%) patients given placebo (who had a median on-treatment LDL-cholesterol concentration of 2.80 mmol/L [IQR 2.43-3.24]), HDL-cholesterol concentrations were inversely related to vascular risk both at baseline (top quartile vs bottom quartile hazard ratio [HR] 0.54, 95% CI 0.35-0.83, p=0.0039) and on-treatment (0.55, 0.35-0.87, p=0.0047). By contrast, among the 8900 (50%) patients given rosuvastatin 20 mg (who had a median on-treatment LDL-cholesterol concentration of 1.42 mmol/L [IQR 1.14-1.86]), no significant relationships were noted between quartiles of HDL-cholesterol concentration and vascular risk either at baseline (1.12, 0.62-2.03, p=0.82) or on-treatment (1.03, 0.57-1.87, p=0.97). Our analyses

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

    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

  2. Essential role of TGF-beta/Smad pathway on statin dependent vascular smooth muscle cell regulation.

    Juan Rodríguez-Vita

    Full Text Available BACKGROUND: The 3-hydroxy-3-methylglutaryl CoA reductase inhibitors (also called statins exert proven beneficial effects on cardiovascular diseases. Recent data suggest a protective role for Transforming Growth Factor-beta (TGF-beta in atherosclerosis by regulating the balance between inflammation and extracellular matrix accumulation. However, there are no studies about the effect of statins on TGF-beta/Smad pathway in atherosclerosis and vascular cells. METHODOLOGY: In cultured vascular smooth muscle cells (VSMCs statins enhanced Smad pathway activation caused by TGF-beta. In addition, statins upregulated TGF-beta receptor type II (TRII, and increased TGF-beta synthesis and TGF-beta/Smad-dependent actions. In this sense, statins, through Smad activation, render VSMCs more susceptible to TGF-beta induced apoptosis and increased TGF-beta-mediated ECM production. It is well documented that high doses of statins induce apoptosis in cultured VSMC in the presence of serum; however the precise mechanism of this effect remains to be elucidated. We have found that statins-induced apoptosis was mediated by TGF-beta/Smad pathway. Finally, we have described that RhoA inhibition is a common intracellular mechanisms involved in statins effects. The in vivo relevance of these findings was assessed in an experimental model of atherosclerosis in apolipoprotein E deficient mice: Treatment with Atorvastatin increased Smad3 phosphorylation and TRII overexpression, associated to elevated ECM deposition in the VSMCs within atheroma plaques, while apoptosis was not detected. CONCLUSIONS: Statins enhance TGF-beta/Smad pathway, regulating ligand levels, receptor, main signaling pathway and cellular responses of VSMC, including apoptosis and ECM accumulation. Our findings show that TGF-beta/Smad pathway is essential for statins-dependent actions in VSMCs.

  3. The effects of 2 weeks of statin treatment on mitochondrial respiratory capacity in middle-aged males: the LIFESTAT study.

    Asping, Magnus; Stride, Nis; Søgaard, Ditte; Dohlmann, Tine Lovsø; Helge, Jørn W; Dela, Flemming; Larsen, Steen

    2017-06-01

    Statins are used to lower cholesterol in plasma and are one of the most used drugs in the world. Many statin users experience muscle pain, but the mechanisms are unknown at the moment. Many studies have hypothesized that mitochondrial function could be involved in these side effects. The aim of the study was to investigate mitochondrial function after 2 weeks of treatment with simvastatin (S; n = 10) or pravastatin (P; n = 10) in healthy middle-aged participants. Mitochondrial respiratory capacity and substrate sensitivity were measured in permeabilized muscle fibers by high-resolution respirometry. Mitochondrial content (citrate synthase (CS) activity), antioxidant content, as well as coenzyme Q 10 concentration (Q 10 ) were determined. Fasting plasma glucose and insulin concentrations were measured, and whole body maximal oxygen uptake (VO 2max ) was determined. No differences were seen in mitochondrial respiratory capacity although a tendency was observed for a reduction when complex IV respiration was analyzed in both S (229 (169; 289 (95% confidence interval)) vs. 179 (146; 211) pmol/s/mg, respectively; P = 0.062) and P (214 (143; 285) vs. 162 (104; 220) pmol/s/mg, respectively; P = 0.053) after treatment. A tendency (1.64 (1.28; 2.00) vs. 1.28 (0.99; 1.58) mM, respectively; P = 0.092) for an increased mitochondrial substrate sensitivity (complex I-linked substrate; glutamate) was seen only in S after treatment. No differences were seen in Q 10 , CS activity, or antioxidant content after treatment. Fasting glucose and insulin as well as VO 2max were not changed after treatment. Two weeks of statin (S or P) treatment have no major effect on mitochondrial function. The tendency for an increased mitochondrial substrate sensitivity after simvastatin treatment could be an early indication of the negative effects linked to statin treatment.

  4. Statin-Induced Rhabdomyolysis: A Comprehensive Review of Case Reports

    Mendes, Polyana; Robles, Priscila Games; Mathur, Sunita

    2014-01-01

    Purpose: To identify case reports of statin-induced rhabdomyolysis and summarize common predisposing factors, symptoms, diagnostic findings, functional outcomes, characteristics, treatment, and rehabilitation. Method: MEDLINE, CINAHL, SCOPUS, and PEDro databases were searched (1990–2013) for relevant case reports using the search terms “Statins,” “Rhabdomyolysis,” “Myalgia,” “Muscle damage,” “Muscle injury,” and “Myopathy.” Relevance (based on title and abstract) was assessed by one investiga...

  5. 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.

    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.

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

    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

  7. Regression of Some High-risk Features of Age-related Macular Degeneration (AMD in Patients Receiving Intensive Statin Treatment

    Demetrios G. Vavvas

    2016-03-01

    Conclusions: High-dose statins may result in resolution of drusenoid pigment epithelial detachments (PEDs and improvement in VA, without atrophy or neovascularization in a high-risk subgroup of AMD patients. Confirmation from larger studies is warranted.

  8. Management of statin-intolerant patient.

    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.

  9. Population-Based Case-Control Study Assessing the Association between Statins Use and Pulmonary Tuberculosis in Taiwan

    Kuan-Fu Liao

    2017-08-01

    Full Text Available Background and Objectives: Little evidence is available about the relationship between statins use and pulmonary tuberculosis in Taiwan. The aim of the study was to explore this issue.Methods: Using the database of the Taiwan National Health Insurance Program, we conducted a population-based case-control study to identify 8,236 subjects aged 20 years and older with newly diagnosed pulmonary tuberculosis from 2000 to 2013 as the cases. We randomly selected 8,236 sex-matched and age-matched subjects without pulmonary tuberculosis as the controls. Subjects who had at least one prescription of statins before the index date were defined as “ever use.” Subjects who never had one prescription of statins before the index date were defined as “never use.” The odds ratio (OR and 95% confidence interval (CI for pulmonary tuberculosis associated with statins use was estimated by a multivariable logistic regression model.Results: After adjustment for co-variables, the adjusted OR of pulmonary tuberculosis was 0.67 for subjects with ever use of statins (95% CI 0.59, 0.75. In a sub-analysis, the adjusted ORs of pulmonary tuberculosis were 0.87 (95% CI 0.69, 1.10 for subjects with cumulative duration of statins use <3 months, 0.77 (95% CI 0.58, 1.03 for 3–6 months, and 0.59 (95% CI 0.51, 0.68 for ≥6 months, compared with subjects with never use of statins.Conclusions: Statins use correlates with a small but statistically significant risk reduction of pulmonary tuberculosis. The protective effect is stronger for longer duration of statins use. Due to a case-control design, a causal-relationship cannot be established in our study. A prospective cohort design is needed to confirm our findings.

  10. Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance.

    Thompson, Paul D; MacDougall, Diane E; Newton, Roger S; Margulies, Janice R; Hanselman, Jeffrey C; Orloff, David G; McKenney, James M; Ballantyne, Christie M

    2016-01-01

    ETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia. To compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg (EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C). This phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE. EZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups. In patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836). Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  11. LIFESTAT – Living with statins

    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...

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

    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.

  13. Safety of statins

    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.

  14. Incidences of insomnia sleep disturbances and nightmares in patients receiving statins as treatment in urban Mumbai, India

    Santosh Gosavi

    2012-11-01

    Full Text Available Objective - To study the incidences of insomnia,sleep disturbances and nightmares in patients receiving statins as treatment.Methodology – A self constructed semi-structured questionnaire was prepared and distributed amongst 300 patients on atorvastatin at the Medicine and Hypertension OPDs at B.Y.L. Nair Charitable Hospital, Mumbai. The questionnaire was designed to note the quality of sleep, incidence and frequency of sleep disturbances and nightmares. The dosage and duration of atorvastatin treatment was also noted and then co-related with the above. Further, 30 patients with the above symptoms were asked to stop taking atorvastatin for 15 days and were asked to report improvements, if any. Results: A definite co-relation was found between atorvastatin and sleep disturbance and nightmares. 13.33% of the patients complained of poor quality of sleep. 22.33% of the patients complained of sleep disturbances. 11.67% of the patients complained of nightmares. There is no significant co-relation between dosage of atorvastatin and the sleep-related side effects. There is a definite and significant co-relation between the duration of atorvastatin treatment and sleep-related side effects. On withdrawal of atorvastatin for 15 days, there was a definite improvement in quality of sleep, sleep disturbances and incidence and frequency of nightmares with complete cessation of nightmares in a majority of cases. Conclusion: There is a definite derogatory effect of atorvastatin on quality of sleep with increase in sleep disturbances and nightmares. There is a significant co-relation between the duration of treatment with atorvastatin and the occurrence of sleep-related side effects. On cessation of the drug, the effects also decrease to a large degree

  15. Incidences of insomnia sleep disturbances and nightmares in patients receiving statins as treatment in urban Mumbai, India

    Abhimanyu Mahajan

    2012-01-01

    Full Text Available Objective - To study the incidences of insomnia,sleep disturbances and nightmares in patients receiving statins as treatment.Methodology – A self constructed semi-structured questionnaire was prepared and distributed amongst 300 patients on atorvastatin at the Medicine and Hypertension OPDs at B.Y.L. Nair Charitable Hospital, Mumbai. The questionnaire was designed to note the quality of sleep, incidence and frequency of sleep disturbances and nightmares. The dosage and duration of atorvastatin treatment was also noted and then co-related with the above. Further, 30 patients with the above symptoms were asked to stop taking atorvastatin for 15 days and were asked to report improvements, if any. Results: A definite co-relation was found between atorvastatin and sleep disturbance and nightmares. 13.33% of the patients complained of poor quality of sleep. 22.33% of the patients complained of sleep disturbances. 11.67% of the patients complained of nightmares. There is no significant co-relation between dosage of atorvastatin and the sleep-related side effects. There is a definite and significant co-relation between the duration of atorvastatin treatment and sleep-related side effects. On withdrawal of atorvastatin for 15 days, there was a definite improvement in quality of sleep, sleep disturbances and incidence and frequency of nightmares with complete cessation of nightmares in a majority of cases. Conclusion: There is a definite derogatory effect of atorvastatin on quality of sleep with increase in sleep disturbances and nightmares. There is a significant co-relation between the duration of treatment with atorvastatin and the occurrence of sleep-related side effects. On cessation of the drug, the effects also decrease to a large degree.

  16. Genetically Guided Statin Therapy

    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

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

    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.

  18. Pleiotropic effects of statins in stroke prevention

    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.

  19. Pleiotropic effects of statins in stroke prevention

    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.

  20. Effect of Simvastatin on Arterial Stiffness in Patients with Statin Myalgia

    Kevin D. Ballard

    2015-01-01

    Full Text Available Statins reduce arterial stiffness but are also associated with mild muscle complaints. It is unclear whether individuals with muscle symptoms experience the same vascular benefit or whether statins affect striated and smooth muscle cells differently. We examined the effect of simvastatin treatment on arterial stiffness in patients who did versus those who did not exhibit muscle symptoms. Patients with a history of statin-related muscle complaints (n=115 completed an 8 wk randomized, double-blind, cross-over trial of daily simvastatin 20 mg and placebo. Serum lipids and pulse wave velocity (PWV were assessed before and after each treatment. Muscle symptoms with daily simvastatin treatment were reported by 38 patients (33%. Compared to baseline, central PWV decreased (P=0.01 following simvastatin treatment but not placebo (drug ∗ time interaction: P=0.047. Changes in central PWV with simvastatin treatment were not influenced by myalgia status or time on simvastatin (P≥0.15. Change in central PWV after simvastatin treatment was inversely correlated with age (r=-0.207, P=0.030, suggesting that advancing age is associated with enhanced statin-mediated arterial destiffening. In patients with a history of statin-related muscle complaints, the development of myalgia with short-term simvastatin treatment did not attenuate the improvement in arterial stiffness.

  1. Systematic review and metaanalysis of statins for heterozygous familial hypercholesterolemia in children: evaluation of cholesterol changes and side effects.

    O'Gorman, Clodagh S

    2012-02-01

    Heterozygous familial hypercholesterolemia (heFH) affects 1 in 500 individuals. Evidence supports the low-density lipoprotein (LDL)-lowering effect of statins for adults with heFH. However, there are concerns regarding the treatment children with heFH. By performing a systematic review and metaanalysis of the published literature, this study aimed to evaluate the efficacy and safety of statins used for children with heFH. A systematic review was performed by searching multiple medical databases and citations to identify reports of randomized controlled trials of statins used to treat children with heFH. The trials were retrieved, reviewed, and subjected to metaanalysis. The search yielded 2,174 titles. Of the 63 studies retrieved and reviewed, 56 were excluded, 7 were included in the systematic review, and 4 were included in the metaanalysis. Significant heterogeneity was detected. The metaanalysis showed significant LDL lowering, high-density lipoprotein (HDL) cholesterol elevation, and increases in height and weight with statins. The metaanalysis could not be performed for many side effects of statins, but individual trials showed no significant side effects. Quality assessment showed methodologic concerns, with potential for bias. For example, six trials analyzed statin effects without intention to treat despite such a stated intention. Metaanalysis shows significant LDL lowering with statin treatment. Further studies, including epidemiologic and multicenter studies, are required.

  2. Statin treatment and mortality in community-dwelling frail older patients with diabetes mellitus : A retrospective observational study

    A. Pilotto (Alberto); F. Panza (Francesco); Copetti, M. (Massimiliano); Simonato, M. (Matteo); D. Sancarlo; P. Gallina (Pietro); T.E. Strandberg (Timo); A.J. Cruz-Jentoft (A.); Daragjati, J. (Julia); L. Ferrucci (Luigi); A. Fontana (Andrea); S. Maggi; F.U.S. Mattace Raso (Francesco); M. Paccalin; Polidori, M.C. (Maria Cristina); Schulz, R.-J. (Ralf-Joachim); E. Topinkova; G. Trifirò (Gianluca); A.-K. Welmer

    2015-01-01

    textabstractBackground: Older adults are often excluded from clinical trials. Decision making for administration of statins to older patients with diabetes mellitus (DM) is under debate, particularly in frail older patients with comorbidity and high mortality risk. We tested the hypothesis that

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

    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

  4. Effect of coenzyme q10 on myopathic symptoms in patients treated with statins.

    Caso, Giuseppe; Kelly, Patricia; McNurlan, Margaret A; Lawson, William E

    2007-05-15

    Treatment of hypercholesterolemia with statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) is effective in the primary and secondary prevention of cardiovascular disease. However, statin use is often associated with a variety of muscle-related symptoms or myopathies. Myopathy may be related in part to statin inhibition of the endogenous synthesis of coenzyme Q10, an essential cofactor for mitochondrial energy production. The aim of this study is to determine whether coenzyme Q10 supplementation would reduce the degree of muscle pain associated with statin treatment. Patients with myopathic symptoms were randomly assigned in a double-blinded protocol to treatment with coenzyme Q10 (100 mg/day, n = 18) or vitamin E (400 IU/day, n = 14) for 30 days. Muscle pain and pain interference with daily activities were assessed before and after treatment. After a 30-day intervention, pain severity decreased by 40% (p pain interference with daily activities decreased by 38% (p pain severity (+9%, p = NS) or pain interference with daily activities (-11%, p = NS) was observed in the group treated with vitamin E. In conclusion, results suggest that coenzyme Q10 supplementation may decrease muscle pain associated with statin treatment. Thus, coenzyme Q10 supplementation may offer an alternative to stopping treatment with these vital drugs.

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

    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

  6. Statin treatment in children with familial hypercholesterolemia - The younger, the better

    Rodenburg, Jessica; Vissers, Maud N.; Wiegman, Albert; van Trotsenburg, A. S. Paul; van der Graaf, Anouk; de Groot, Eric; Wijburg, Frits A.; Kastelein, John J. P.; Hutten, Barbara A.

    2007-01-01

    Background - We previously demonstrated in a randomized placebo- controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these

  7. Equity in statin use in New Zealand

    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.

  8. A review of the potential therapeutic role of statins in the treatment of Alzheimer’s disease: current research and opinion

    Mitchell AJ

    2013-01-01

    Full Text Available Álvaro Sánchez-Ferro,1–4 Julián Benito-León,1–3 Alex J Mitchell,5 Félix Bermejo-Pareja1–31Department of Neurology, University Hospital 12 de Octubre, Madrid, Spain; 2Department of Medicine, Complutense University, Madrid, Spain; 3Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas, Madrid, Spain; 4Instituto de Salud Carlos III, Madrid, Spain; 5Department of Psycho-oncology, Leicestershire Partnership NHS Trust and University of Leicester, Leicester, UKAbstract: Alzheimer’s disease is one of the most prevalent neurodegenerative disorders. However, there is no current treatment, which definitively influences disease progression over a sustained period. Numerous studies linking an increase in serum cholesterol, mainly during midlife, with the pathogenic process of Alzheimer’s disease have been published. Therefore, the role of statins as a therapy in this disorder may be of great interest. The aim of the present review is to summarize of the role of statins in the treatment of Alzheimer’s disease.Keywords: animal models, epidemiology, HMGCoA-inhibitors, clinical trials, prevention, cognitive function

  9. Association of statin use with a pathologic complete response to neoadjuvant chemoradiation for rectal cancer

    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

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

    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.

  11. Role of Statin Drugs for Polycystic Ovary Syndrome.

    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.

  12. Role of Statin Drugs for Polycystic Ovary Syndrome

    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. 

  13. Impact of Statin Use on Outcomes in Triple Negative Breast Cancer

    Shaitelman, Simona F.; Stauder, Michael C.; Allen, Pamela; Reddy, Sangeetha; Lakoski, Susan; Atkinson, Bradley; Reddy, Jay; Amaya, Diana; Guerra, William; Ueno, Naoto; Caudle, Abigail; Tereffe, Welela; Woodward, Wendy A.

    2017-01-01

    Purpose: We sought to investigate if the use of HMG Co-A reductase inhibitors (statins) has an impact on outcomes among patients with triple negative breast cancer (TNBC). Methods: We reviewed the cases of women with invasive, non-metastatic TNBC, diagnosed 1997-2012. Clinical outcomes were compared based on statin use (defined as ever use during treatment vs. never use). We identified a subset of women for whom a 5-value lipid panel (5VLP) was available, including total cholesterol, low density lipoprotein, high density lipoprotein, very low density lipoprotein, and triglycerides. The Kaplan-Meier method was used to estimate median overall survival (OS), distant metastases-free survival (DMFS), and local-regional recurrence-free survival (LRRFS). A Cox proportional hazards regression model was used to test the statistical significance of prognostic factors. Results: 869 women were identified who met inclusion criteria, with a median follow-up time of 75.1 months (range 2.4-228.9 months). 293 (33.7%) patients used statins and 368 (42.3%) had a 5VLP. OS, DMFS, and LRRFS were not significant based on statin use or type. Controlling for the 5VLP values, on multivariable analysis, statin use was significantly associated with OS (HR 0.10, 95% CI 0.01-0.76), but not with DMFS (HR 0.14, 95% CI 0.01-1.40) nor LRRFS (HR 0.10 95% CI 0.00-3.51). Conclusions: Statin use among patients with TNBC is not associated with improved OS, although it may have a benefit for a subset of patients. Prospective assessment would be valuable to better assess the potential complex correlation between clinical outcome, lipid levels, and statin use. PMID:28819403

  14. Statins and Cancer Prevention

    ... 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? ...

  15. Statin resistance and export

    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...

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

    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....

  17. Pre-stroke use of statins on stroke outcome : a meta-analysis of observational studies

    Cordenier, Ann; De Smedt, Ann; Brouns, Raf; Uyttenboogaart, Maarten; De Raedt, Sylvie; Luijckx, Gert-Jan; De Keyser, Jacques

    2011-01-01

    Background: Animal pre-clinical studies suggest that statins may have neuroprotective effects in acute ischaemic stroke. Statins might also increase the risk of developing haemorrhagic transformation after thrombolytic treatment. Methods: We performed a systematic review and included studies that

  18. Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis.

    Brinton, Eliot A; Ballantyne, Christie M; Guyton, John R; Philip, Sephy; Doyle, Ralph T; Juliano, Rebecca A; Mosca, Lori

    2018-03-27

    High triglycerides (TG) and diabetes mellitus type 2 (DM2) are stronger predictors of cardiovascular disease (CVD) in women than in men, but few randomized, controlled clinical trials have investigated lipid-lowering interventions in women and none have reported results specifically in women with high TG and DM2. Icosapent ethyl (Vascepa) is pure prescription eicosapentaenoic acid (EPA) ethyl ester approved at 4 g/day as an adjunct to diet to reduce TG ≥500 mg/dL. The 12-week ANCHOR trial randomized 702 statin-treated patients (73% with DM; 39% women) at increased CVD risk with TG 200-499 mg/dL despite controlled low-density lipoprotein cholesterol (LDL-C; 40-99 mg/dL) to receive icosapent ethyl 2 g/day, 4 g/day, or placebo. This post hoc analysis included 146 women with DM2 (97% white, mean age 62 years) randomized to icosapent ethyl 4 g/day (n = 74) or placebo (n = 72). Icosapent ethyl significantly reduced TG (-21.5%; p women with DM2 at high CVD risk with persistently high TG on statins, icosapent ethyl 4 g/day reduced potentially atherogenic parameters with safety and tolerability comparable to placebo. Potential CVD benefits of icosapent ethyl are being tested in ∼8000 men and women at high CVD risk with high TG on statins in the ongoing Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial (REDUCE-IT) cardiovascular (CV) outcome trial.

  19. Statins improve NASH via inhibition of RhoA and Ras

    Schierwagen, Robert; Maybüchen, Lara; Hittatiya, Kanishka

    2016-01-01

    . Hepatic steatosis, inflammation, and fibrosis were assessed by histology, Western blot, and RT-PCR measurements of cholesterol and hydroxyproline content. SMV treatment significantly decreased hepatic inflammation and fibrosis, but had no significant effect on steatosis and hepatic cholesterol content...... by statins is responsible for the beneficial hepatic effects in NASH....

  20. Statin Induced Myopathy a Patient with Multiple Systemic Diseases

    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.

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

    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.

  2. Do immigrants from Turkey, Pakistan and Yugoslavia receive adequate medical treatment with beta-blockers and statins after acute myocardial infarction compared with Danish-born residents? A register-based follow-up study

    Hempler, Nana Folmann; Diderichsen, Finn; Larsen, Finn Breinholt

    2010-01-01

    We undertook a study investigating whether immigrants from Turkey, Pakistan and Yugoslavia received adequate medical treatment with beta-blockers and statins after acute myocardial infarction (AMI) when compared with Danish-born residents and explored whether associations between patient origin...

  3. Safety of statins.

    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.

  4. Estimation of Missed Statin Prescription Use in an Administrative Claims Dataset.

    Wade, Rolin L; Patel, Jeetvan G; Hill, Jerrold W; De, Ajita P; Harrison, David J

    2017-09-01

    Nonadherence to statin medications is associated with increased risk of cardiovascular disease and poses a challenge to lipid management in patients who are at risk for atherosclerotic cardiovascular disease. Numerous studies have examined statin adherence based on administrative claims data; however, these data may underestimate statin use in patients who participate in generic drug discount programs or who have alternative coverage. To estimate the proportion of patients with missing statin claims in a claims database and determine how missing claims affect commonly used utilization metrics. This retrospective cohort study used pharmacy data from the PharMetrics Plus (P+) claims dataset linked to the IMS longitudinal pharmacy point-of-sale prescription database (LRx) from January 1, 2012, through December 31, 2014. Eligible patients were represented in the P+ and LRx datasets, had ≥1 claim for a statin (index claim) in either database, and had ≥ 24 months of continuous enrollment in P+. Patients were linked between P+ and LRx using a deterministic method. Duplicate claims between LRx and P+ were removed to produce a new dataset comprised of P+ claims augmented with LRx claims. Statin use was then compared between P+ and the augmented P+ dataset. Utilization metrics that were evaluated included percentage of patients with ≥ 1 missing statin claim over 12 months in P+; the number of patients misclassified as new users in P+; the number of patients misclassified as nonstatin users in P+; the change in 12-month medication possession ratio (MPR) and proportion of days covered (PDC) in P+; the comparison between P+ and LRx of classifications of statin treatment patterns (statin intensity and patients with treatment modifications); and the payment status for missing statin claims. Data from 965,785 patients with statin claims in P+ were analyzed (mean age 56.6 years; 57% male). In P+, 20.1% had ≥ 1 missing statin claim post-index; 13.7% were misclassified as

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

    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...

  6. Cholesterol - drug treatment

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  7. Statin myopathy: the fly in the ointment for the prevention of cardiovascular disease in the 21st century?

    Keen, Helen I; Krishnarajah, Janakan; Bates, Timothy R; Watts, Gerald F

    2014-09-01

    Cardiovascular disease (CVD) remains the leading cause of death in industrialized nations. Despite clear evidence of CVD risk reduction with HMG-CoA reductase inhibitors (statins), the side effects of these medications, particularly myopathy, limit their effectiveness. Studies into the mechanisms, aetiology and management of statin myopathy are limited by lack of an internationally agreed clinical definition and tools for assessing outcomes. Currently there is a paucity of evidence to guide the management of patients affected by statin myopathy; with the exception of dose reduction, there is little evidence that other strategies can improve statin tolerance, and even less evidence to suggest these alternate dosing strategies reduce cardiovascular risk. This review will cover current definitions, clinical presentations, risk factors, pathogenesis and management. PubMed was searched (English language, to 2014) for key articles pertaining to statin myopathy. This review then briefly describes our experience of managing this condition in a tertiary lipid disorders clinic, in the setting of limited guiding evidence. Knowledge gaps in the field of statin myopathy are identified and future research directions are suggested. We urge the need for international attention to address this important, but largely neglected clinical problem, that if unresolved will remain an impediment to the effective prevention and treatment of CVD.

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

    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.

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

    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...

  10. A hypothesis about the potential role of statin administration as adjuvant treatment in the management of Merlin-deficient tumors

    Alexandros G. Brotis, MD, PhD

    2014-03-01

    Full Text Available Merlin, a tumor suppressor protein, controls essential steps of cell cycle, and its deficiency results in cellular overgrowth, proliferation, angiogenesis, invasion and metastasis. Lack of Merlin is responsible for neurofibromatosis-2, most schwannomas, and many meningiomas and ependymomas. We hypothesize that there is a role for statins to ameliorate Merlin's deficiency in this set of tumors by inhibiting a number of Merlin's downstream effectors, the small Rho-GTP-ases, and we present the relevant data. The ultimate goal is to offer a medical therapy promising to halt or reduce the tumor growth-rate in patients harboring Merlin-deficient neoplasms and to provide an adjuvant systemic therapy for patients undergoing stereotactic radio-surgery and partial tumor resection.

  11. Time to improve statin prescription guidelines in low-risk patients?

    Balder, Jan W.; de Vries, Jeroen K.; Mulder, Douwe J.; Kamphuisen, Pieter W.

    Background The challenge of the primary prevention of cardiovascular disease (CVD) is to identify patients who would benefit from treatment with statins. Statins are currently prescribed to many patients, even those at a low 10-year risk of CVD. These latter patients may not be eligible for statins

  12. Controlling Cholesterol with Statins

    ... 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 ...

  13. Statins: pros and cons.

    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.

  14. The case for statin therapy in chronic heart failure

    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).

  15. Statin Effects on Aggression: Results from the UCSD Statin Study, a Randomized Control Trial

    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

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

    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

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

    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

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

    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

  19. Clinical utility of rosuvastatin and other statins for cardiovascular risk reduction among the elderly

    Sydney B Long

    2010-12-01

    Full Text Available Sydney B Long, Michael J Blaha, Roger S Blumenthal, Erin D MichosJohns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USAAbstract: Age is one of the strongest predictors of cardiovascular disease (CVD risk. Treatment with statins can significantly reduce CVD events and mortality in both primary and secondary prevention. Yet despite the high CVD risk among the elderly, there is underutilization of statins in this population (ie, the treatment-risk paradox. Few studies have investigated the use of statins in the elderly, particularly for primary prevention and, as a result, guidelines for treating the elderly are limited. This is likely due to: uncertainties of risk assessment in older individuals where the predictive value of individual risk factors is decreased; the need to balance the benefits of primary prevention with the risks of polypharmacy, health care costs, and adverse medication effects in a population with decreased life expectancy; the complexity of treating patients with many other comorbidities; and increasingly difficult social and economic concerns. As life expectancy increases and the total elderly population grows, these issues become increasingly important. JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin is the largest primary prevention statin trial to date and enrolled a substantial number of elderly adults. Among the 5695 JUPITER participants ≥70 years of age, the absolute CVD risk reduction associated with rosuvastatin was actually greater than for younger participants. The implications of this JUPITER subanalysis and the broader role of statins among older adults is the subject of this review.Keywords: JUPITER, rosuvastatin, elderly, risk

  20. Efficacy of short-term high-dose statin in preventing contrast-induced nephropathy: a meta-analysis of seven randomized controlled trials.

    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.

  1. Statin and Atrial Fibrilation: When does it work?

    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.

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

    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

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

    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.

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

    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.

  5. Residual Cardiovascular Risk in Diabetic Patients: The Role of Fibrate Statin Combination

    Angelos Liontos

    2014-10-01

    Full Text Available Patients with Type 2 diabetes mellitus (T2DM have increased cardiovascular disease (CVD risk. The use of statins significantly reduces the rate of CVD events but many T2DM patients, especially those with mixed dyslipidaemia (MD, have residual CVD risk. The use of fibrates, which improve triglyceride and high-density lipoprotein cholesterol levels, is beneficial for the treatment of patients with MD. Evidence from the Action to Control Cardiovascular Risk in Diabetes (ACCORD Lipid study showed a possible beneficial effect on CVD events of the addition of fenofibrate (FF to statin treatment in patients with T2DM and atherogenic MD. Furthermore, FF has been associated with slowing of the progression of early diabetic retinopathy. The combination of statin with a fibrate may improve the residual CVD risk and microvascular complications of patients with T2DM. However, trials specifically designed to assess the effects of fibrate-statin combination on cardiovascular outcomes in patients with T2DM are missing.

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

    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.

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

    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.

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

    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.

  9. How to take statins

    ... 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

  10. Statins and polyneuropathy revisited

    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...

  11. Statins: Evidence for effectiveness

    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 ...

  12. Hypercholesterolemia, Stroke And Statins

    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.

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

    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.

  14. Is there really a relationship between serum vitamin D (25OHD) levels and the musculoskeletal pain associated with statin intake? A systematic review.

    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.

  15. Statin-associated immune-mediated myopathy: biology and clinical implications.

    Christopher-Stine, Lisa; Basharat, Pari

    2017-04-01

    In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

  16. Pharmacogenomics of sterol synthesis and statin use in schizophrenia subjects treated with antipsychotics.

    Vassas, Thomas J; Burghardt, Kyle J; Ellingrod, Vicki L

    2014-01-01

    Patients with schizophrenia treated with antipsychotics often develop metabolic side effects including dyslipidemia. Antipsychotics potentially upregulate gene expression of a lipid metabolism pathway protein called SREBP via SREB transcription factors (SREBFs). Genetic variation within SREBF may contribute to dyslipidemias and lipid medication efficacy within schizophrenia. A cross-sectional study of 157 patients were genotyped for SREBF1 (rs11868035) and SREBF2 (rs1057217) variants, and assessed for fasting lipids. The cohort's mean age was 46.6 years, was 64% male and 86% were using atypical antipsychotics. When stratified by statin use, those receiving a statin and carrying the SREBF1 T allele exhibited higher total cholesterol levels (p = 0.01), triglyceride levels (p = 0.04) and low-density lipoprotein levels (p = 0.03). A regression analysis controlling for gender differences in lipids showed that the SREBF1 T allele and statin interaction remained only for total cholesterol levels (F[4,149] = 5.8; p < 0.0001). For schizophrenia individuals with the SREBF1 rs11868035 T allele, incomplete response to statin medications may be seen. Future investigations may allow for personalizing dyslipidemia treatment based on pharmacogenetics within schizophrenia.

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

    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.

  18. Statins and oxidative stress in the cardiovascular system.

    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.

  19. Statin use and peripheral sensory perception: a pilot study.

    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.

  20. Are pleiotropic effects of statins real?

    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

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

    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.

  2. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    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.

  3. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    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.

  4. Statin Utilization and Recommendations Among HIV- and HCV-infected Veterans: A Cohort Study.

    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.

  5. Protective effects of a squalene synthase inhibitor, lapaquistat acetate (TAK-475), on statin-induced myotoxicity in guinea pigs

    Nishimoto, Tomoyuki; Ishikawa, Eiichiro; Anayama, Hisashi; Hamajyo, Hitomi; Nagai, Hirofumi; Hirakata, Masao; Tozawa, Ryuichi

    2007-01-01

    High-dose statin treatment has been recommended as a primary strategy for aggressive reduction of LDL cholesterol levels and protection against coronary artery disease. The effectiveness of high-dose statins may be limited by their potential for myotoxic side effects. There is currently little known about the molecular mechanisms of statin-induced myotoxicity. Previously we showed that T-91485, an active metabolite of the squalene synthase inhibitor lapaquistat acetate (lapaquistat: a previous name is TAK-475), attenuated statin-induced cytotoxicity in human skeletal muscle cells [Nishimoto, T., Tozawa, R., Amano, Y., Wada, T., Imura, Y., Sugiyama, Y., 2003a. Comparing myotoxic effects of squalene synthase inhibitor, T-91485, and 3-hydroxy-3-methylglutaryl coenzyme A. Biochem. Pharmacol. 66, 2133-2139]. In the current study, we investigated the effects of lapaquistat administration on statin-induced myotoxicity in vivo. Guinea pigs were treated with either high-dose cerivastatin (1 mg/kg) or cerivastatin together with lapaquistat (30 mg/kg) for 14 days. Treatment with cerivastatin alone decreased plasma cholesterol levels by 45% and increased creatine kinase (CK) levels by more than 10-fold (a marker of myotoxicity). The plasma CK levels positively correlated with the severity of skeletal muscle lesions as assessed by histopathology. Co-administration of lapaquistat almost completely prevented the cerivastatin-induced myotoxicity. Administration of mevalonolactone (100 mg/kg b.i.d.) prevented the cerivastatin-induced myotoxicity, confirming that this effect is directly related to HMG-CoA reductase inhibition. These results strongly suggest that cerivastatin-induced myotoxicity is due to depletion of mevalonate derived isoprenoids. In addition, squalene synthase inhibition could potentially be used clinically to prevent statin-induced myopathy

  6. HMG CoA reductase inhibitors (statins for people with chronic kidney disease not requiring dialysis

    Suetonia C. Palmer

    Full Text Available ABSTRACT BACKGROUND: Cardiovascular disease (CVD is the most frequent cause of death in people with early stages of chronic kidney disease (CKD, for whom the absolute risk of cardiovascular events is similar to people who have existing coronary artery disease. This is an update of a review published in 2009, and includes evidence from 27 new studies (25,068 participants in addition to the 26 studies (20,324 participants assessed previously; and excludes three previously included studies (107 participants. This updated review includes 50 studies (45,285 participants; of these 38 (37,274 participants were meta-analysed. OBJECTIVES: To evaluate the benefits (such as reductions in all-cause and cardiovascular mortality, major cardiovascular events, MI and stroke; and slow progression of CKD to end-stage kidney disease (ESKD and harms (muscle and liver dysfunction, withdrawal, and cancer of statins compared with placebo, no treatment, standard care or another statin in adults with CKD who were not on dialysis. METHODS: Search methods: We searched the Cochrane Renal Group's Specialised Register to 5 June 2012 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Selection criteria: Randomised controlled trials (RCTs and quasi-RCTs that compared the effects of statins with placebo, no treatment, standard care, or other statins, on mortality, cardiovascular events, kidney function, toxicity, and lipid levels in adults with CKD not on dialysis were the focus of our literature searches. Data collection and analysis: Two or more authors independently extracted data and assessed study risk of bias. Treatment effects were expressed as mean difference (MD for continuous outcomes (lipids, creatinine clearance and proteinuria and risk ratio (RR for dichotomous outcomes (major cardiovascular events, all-cause mortality, cardiovascular mortality, fatal or non-fatal myocardial infarction (MI, fatal or non-fatal stroke

  7. Applying Multiple Criteria Decision Analysis to Comparative Benefit-Risk Assessment : Choosing among Statins in Primary Prevention

    Tervonen, Tommi; Naci, Huseyin; van Valkenhoef, Gert; Ades, Anthony E.; Angelis, Aris; Hillege, Hans L.; Postmus, Douwe

    2015-01-01

    Decision makers in different health care settings need to weigh the benefits and harms of alternative treatment strategies. Such health care decisions include marketing authorization by regulatory agencies, practice guideline formulation by clinical groups, and treatment selection by prescribers and

  8. Use of principal component analysis in the evaluation of adherence to statin treatment: a method to determine a potential target population for public health intervention.

    Latry, Philippe; Martin-Latry, Karin; Labat, Anne; Molimard, Mathieu; Peter, Claude

    2011-08-01

    The prevalence of statin use is high but adherence low. For public health intervention to be rational, subpopulations of nonadherent subjects must be defined. To categorise statin users with respect to patterns of reimbursement, this study was performed using the main French health reimbursement database for the Aquitaine region of south-western France. The cohort included subjects who submitted a reimbursement for at least one delivery of a statin (index) during the inclusion period (1st of September 2004-31st of December 2004). Indicators of adherence from reimbursement data were considered for principal component analysis. The 119,570 subjects included and analysed had a sex ratio of 1.1, mean (SD) age of 65.9 (11.9), and 13% were considered incident statin users. Principal component analysis found three dimensions that explained 67% of the variance. Using a K-means classification combined with a hierarchical ascendant classification, six groups were characterised. One group was considered nonadherent (10% of study population) and one group least adherent (1%). This novel application of principal component analysis identified groups that may be potential targets for intervention. The least adherent group appears to be one of the most appropriate because of both its relatively small size for case review with prescribing physicians and its very poor adherence. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

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

    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.

  10. The effect of statins on influenza-like illness morbidity and mortality.

    Brassard, Paul; Wu, Jennifer W; Ernst, Pierre; Dell'Aniello, Sophie; Smiechowski, Brielan; Suissa, Samy

    2017-01-01

    The effect of statins on cytokine-mediated inflammatory responses may impact on the prognosis of influenza. We assessed whether statin use decreases the incidence of adverse influenza-related outcomes. Additionally, we used a new-user study design to minimize healthy user bias. We further examined the possibility of non-causal associations by using unrelated outcomes. We used the UK Clinical Practice Research Datalink to identify all patients aged 30 or older diagnosed with influenza-like illness during 1997-2010. Statin users were compared with propensity score-matched patients not receiving statins. The outcome was hospitalization for influenza or pneumonia or death in the 30 days following influenza diagnosis. Logistic regression estimated cumulative incidence ratios. The study cohort included 5181 statin users matched to 5181 non-users. The 30-day incidence of hospitalization or death was 3.5% in statin users and 5.2% in non-users, resulting in a 27% lower incidence with statin use (cumulative incidence ratio: 0.73, 95%CI: 0.59-0.89). New statin users were less protected against our composite outcome. The effect of statins was less pronounced among those with respiratory and cardiac disease. Statin use was shown to be associated with a non-statistically significant risk reduction of motor vehicle accident and burns. The attenuation of the effect of statins with the new-user design, supporting evidence from the assessment of effect modification, and additional sub-analyses evaluating the effect of statins on non-related outcomes suggest that the beneficial effect of statins on influenza-related adverse outcomes may be explained by a healthy user bias. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

    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.

  12. STATINS AND MYOPATHY: MOLECULAR MECHANISMS

    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. 

  13. Genetic determinants of statin intolerance

    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.

  14. Statin therapy for the octogenarian?

    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.

  15. Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

    Fukuda, Kazuki [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Nakao, Saya [Department of Environmental & Symbiotic Sciences, Prefectural University of Kumamoto, Kumamoto (Japan); Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Kawada, Teruo [Laboratory of Nutrition Chemistry, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto (Japan); Nishikawa, Takeshi; Araki, Eiichi [Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

    2015-01-30

    Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe{sup −/−} mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe{sup −/−} mice. In conclusion, statins mediate anti-atherogenic effects

  16. Statins meditate anti-atherosclerotic action in smooth muscle cells by peroxisome proliferator-activated receptor-γ activation

    Fukuda, Kazuki; Matsumura, Takeshi; Senokuchi, Takafumi; Ishii, Norio; Kinoshita, Hiroyuki; Yamada, Sarie; Murakami, Saiko; Nakao, Saya; Motoshima, Hiroyuki; Kondo, Tatsuya; Kukidome, Daisuke; Kawasaki, Shuji; Kawada, Teruo; Nishikawa, Takeshi; Araki, Eiichi

    2015-01-01

    Highlights: • Statins induce PPARγ activation in vascular smooth muscle cells. • Statin-induced PPARγ activation is mediated by COX-2 expression. • Statins suppress cell migration and proliferation in vascular smooth muscle cells. • Statins inhibit LPS-induced inflammatory responses by PPARγ activation. • Fluvastatin suppress the progression of atherosclerosis and induces PPARγ activation in the aorta of apoE-deficient mice. - Abstract: The peroxisome proliferator-activated receptor-γ (PPARγ) is an important regulator of lipid and glucose metabolism, and its activation is reported to suppress the progression of atherosclerosis. We have reported that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) activate PPARγ in macrophages. However, it is not yet known whether statins activate PPARγ in other vascular cells. In the present study, we investigated whether statins activate PPARγ in smooth muscle cells (SMCs) and endothelial cells (ECs) and thus mediate anti-atherosclerotic effects. Human aortic SMCs (HASMCs) and human umbilical vein ECs (HUVECs) were used in this study. Fluvastatin and pitavastatin activated PPARγ in HASMCs, but not in HUVECs. Statins induced cyclooxygenase-2 (COX-2) expression in HASMCs, but not in HUVECs. Moreover, treatment with COX-2-siRNA abrogated statin-mediated PPARγ activation in HASMCs. Statins suppressed migration and proliferation of HASMCs, and inhibited lipopolysaccharide-induced expression of monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-α (TNF-α) in HASMCs. These effects of statins were abrogated by treatment with PPARγ-siRNA. Treatment with statins suppressed atherosclerotic lesion formation in Apoe −/− mice. In addition, transcriptional activity of PPARγ and CD36 expression were increased, and the expression of MCP-1 and TNF-α was decreased, in the aorta of statin-treated Apoe −/− mice. In conclusion, statins mediate anti-atherogenic effects through PPAR

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

    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.

  18. Statin use decreases coagulation in users of vitamin K antagonists.

    van Rein, Nienke; Biedermann, J S; Bonafacio, S M; Kruip, M J H A; van der Meer, F J M; Lijfering, W M

    2016-12-01

    The purpose of the study is to determine the immediate and long-term effect of statins on coagulation in patients treated with vitamin K antagonists (VKAs). We selected patients on VKAs of two Dutch anticoagulation clinics who initiated treatment with a statin between 2009 and 2013. Patients who initiated or stopped concomitant drugs that interact with VKAs or were hospitalised during follow-up were excluded. The VKA dosage (mg/day) after statin initiation was compared with the last VKA dosage before the statin was started. Immediate and long-term differences in VKA dosage (at 6 and 12 weeks) were calculated with a paired student t test. Four hundred thirty-five phenprocoumon users (mean age 70 years, 60 % men) and 303 acenocoumarol users (mean age 69 years, 58 % men) were included. After start of statin use, the immediate phenprocoumon dosage was 0.02 mg/day (95 % CI, 0.00 to 0.03) lower. At 6 and 12 weeks, these phenprocoumon dosages were 0.03 (95 % CI, 0.01 to 0.05) and 0.07 mg/day (95 % CI, 0.04 to 0.09) lower as compared with the dosage before first statin use. In acenocoumarol users, VKA dosage was 0.04 mg/day (95%CI, 0.01 to 0.07) (immediate effect), 0.10 (95 % CI, 0.03 to 0.16) (at 6 weeks), and 0.11 mg/day (95 % CI, 0.04 to 0.18) (after 12 weeks) lower. Initiation of statin treatment was associated with an immediate and long-term minor although statistically significant decrease in VKA dosage in both phenprocoumon and acenocoumarol users, which suggests that statins may have anticoagulant properties.

  19. Switching statins in Norway after new reimbursement policy: a nationwide prescription study.

    Sakshaug, Solveig; Furu, Kari; Karlstad, Øystein; Rønning, Marit; Skurtveit, Svetlana

    2007-10-01

    To assess the changes in prescribing of statins in Norway after implementation of the new reimbursement regulations for statins in June 2005. Data were retrieved from the Norwegian Prescription Database covering the total population in Norway (4.6 million). Outcome measures were the proportion of atorvastatin users switching to simvastatin and changes in the proportion of new statin users receiving simvastatin. Based on retail costs for all statin prescriptions dispensed in Norway, expenditure was measured in Norwegian currency. One-year prevalences of statin use increased from 6.3 to 6.8% for women and from 7.5 to 8.1% for men from the year before to the year after the new statin regulations. Of atorvastatin users (N = 131,222), 39% switched to simvastatin during the 13-month period after the implementation. The proportion of switching was higher in women (41%) than in men (36%). In May 2005, 48% of the new statin users received simvastatin. The proportion of new users receiving simvastatin increased rapidly after implementation of the new regulations to 68% in June 2005 and reached 92% in June 2006. Expenditure was reduced from 120 million to 95 million Euro when comparing the year before with the year after the new statin regulations. The new reimbursement policy for statins has had a great impact on physicians' prescribing of statins in Norway. Physicians in Norway acknowledge the importance of contributing to cost containment.

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

    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.

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

    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.

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

    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.

  3. Statins for age-related macular degeneration.

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2015-02-11

    Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the included studies. Two RCTs with 144 total participants met the selection criteria

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

    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.

  5. Comparison of PCSK9 Inhibitor Evolocumab vs Ezetimibe in Statin-Intolerant Patients

    Nissen, Steven E; Dent-Acosta, Ricardo E; Rosenson, Robert S

    2016-01-01

    -controlled study to compare effectiveness of 24 weeks of evolocumab 420 mg monthly vs ezetimibe 10 mg daily in hypercholesterolemic patients unable to tolerate an effective statin dose. The study incorporates a novel atorvastatin-controlled, double-blind, crossover phase to objectively identify statin intolerance....... Eligible patients had LDL-C above the National Cholesterol Education Project Adult Treatment Panel III target level for the appropriate coronary heart disease risk category and were unable to tolerate ≥3 statins or 2 statins (one of which was atorvastatin ≤10 mg/d) or had a history of marked creatine...

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

    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.

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

    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.

  8. Switching statins in Norway after new reimbursement policy – a nationwide prescription study

    Sakshaug, Solveig; Furu, Kari; Karlstad, Øystein; Rønning, Marit; Skurtveit, Svetlana

    2007-01-01

    What is already known about this subject Use of statins is growing worldwide and costs represent a burden to public budgets. The introduction of simvastatin generics, generic substitution and price regulations have contributed to price reductions and resulted in overall cost reductions of statin use in Norway. What this study adds New reimbursement regulations for statins in Norway in June 2005, making simvastatin the drug of choice, had a great impact on physicians' prescribing of statins. Nearly 40% of the atorvastatin users switched to simvastatin during the 13-month period after implementation of the new regulations. Among the new users of statins the proportion receiving simvastatin increased from 48% in May 2005 to 92% in June 2006. The new regulations have reduced costs of statins, even though the prevalence of statin use has increased. Aims To assess the changes in prescribing of statins in Norway after implementation of the new reimbursement regulations for statins in June 2005. Methods Data were retrieved from the Norwegian Prescription Database covering the total population in Norway (4.6 million). Outcome measures were the proportion of atorvastatin users switching to simvastatin and changes in the proportion of new statin users receiving simvastatin. Based on retail costs for all statin prescriptions dispensed in Norway, expenditure was measured in Norwegian currency. Results One-year prevalences of statin use increased from 6.3 to 6.8% for women and from 7.5 to 8.1% for men from the year before to the year after the new statin regulations. Of atorvastatin users (N = 131 222), 39% switched to simvastatin during the 13-month period after the implementation. The proportion of switching was higher in women (41%) than in men (36%). In May 2005, 48% of the new statin users received simvastatin. The proportion of new users receiving simvastatin increased rapidly after implementation of the new regulations to 68% in June 2005 and reached 92% in June 2006

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

    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.

  10. A content analysis of the representation of statins in the British newsprint media.

    Chisnell, Julia; Marshall, Tom; Hyde, Chris; Zhelev, Zhivko; Fleming, Lora E

    2017-08-21

    This study reviewed the news media coverage of statins, seeking to identify specific trends or differences in viewpoint between media outlets and examine common themes. The study is a content analysis of the frequency and content of the reporting of statins in a selection of the British newsprint media. It involved an assessment of the number, timing and thematic content of articles followed by a discourse analysis examining the underlying narratives. The sample was the output of four UK newspapers, covering a broad-spectrum readership, over a six month timeframe 1 October 2013 to 31 March 2014. A total of 67 articles included reference to statins. The majority (39, 58%) were reporting or responding to publication of a clinical study. The ratio of negative to positive coverage was greater than 2:1 overall. In the more politically right-leaning newspapers, 67% of coverage was predominantly negative (30/45 articles); 32% in the more left-leaning papers (7/22 articles). Common themes were the perceived 'medicalisation' of the population; the balance between lifestyle modification and medical treatments in the primary prevention of heart disease; side effects and effectiveness of statins; pharmaceutical sponsorship and implications for the reliability of evidence; trust between the public and government, institutions, research organisations and the medical profession. Newsprint media coverage of statins was substantially influenced by the publication of national guidance and by coverage in the medical journals of clinical studies and comment. Statins received a predominantly negative portrayal, notably in the more right-leaning press. There were shared themes: concern about the balance between medication and lifestyle change in the primary prevention of heart disease; the adverse effects of treatment; and a questioning of the reliability of evidence from research institutions, scientists and clinicians in the light of their potential allegiances and funding. © Article

  11. Treatment planning source assessment

    Calzetta Larrieu, O.; Blaumann, H.; Longhino, J.

    2000-01-01

    The reactor RA-6 NCT system was improved during the last year mainly in two aspects: the facility itself getting lower contamination factors and using better measurements techniques to obtain lower uncertainties in its characterization. In this job we show the different steps to get the source to be used in the treatment planning code representing the NCT facility. The first one was to compare the dosimetry in a water phantom between the calculation using the entire facility including core, filter and shields and a surface source at the end of the beam. The second one was to transform this particle by particle source in a distribution one regarding the minimum spatial, energy and angular resolution to get similar results. Finally we compare calculation and experimental values with and without the water phantom to adjust the distribution source. The results are discussed. (author)

  12. Statiner ved akut koronart syndrom--en gennemgang af et Cochranereview

    Linde, Jesper James; Jensen, Gorm Boje

    2012-01-01

    infarction and stroke, but at four-month follow-up the incidence of unstable angina pectoris was significantly reduced. Despite the lack of evidence for an additional effect of early statin administrations on hard clinical end points, we find good reasons to maintain statins in the early treatment of ACS....

  13. Prognostic impact of preoperative statin use after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

    Lim, Ju Hyun; Jeong, In Gab; Park, Jong Yeon; You, Dalsan; Hong, Bumsik; Hong, Jun Hyuk; Ahn, Hanjong; Kim, Choung-Soo

    2015-07-01

    The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.

  14. Evaluation of Trace Elements in Augmentation of Statin-Induced Cytotoxicity in Uremic Serum-Exposed Human Rhabdomyosarcoma Cells

    Hitoshi Uchiyama

    2018-01-01

    Full Text Available Patients with end-stage kidney disease (ESKD are at higher risk for rhabdomyolysis induced by statin than patients with normal kidney function. Previously, we showed that this increase in the severity of statin-induced rhabdomyolysis was partly due to uremic toxins. However, changes in the quantity of various trace elements in ESKD patients likely contribute as well. The purpose of this study is to determine the effect of trace elements on statin-induced toxicity in rhabdomyosarcoma cells exposed to uremic serum (US cells for a long time. Cell viability, apoptosis, mRNA expression, and intracellular trace elements were assessed by viability assays, flow cytometry, real-time RT-PCR, and ICP-MS, respectively. US cells exhibited greater simvastatin-induced cytotoxicity than cells long-time exposed with normal serum (NS cells (non-overlapping 95% confidence intervals. Intracellular levels of Mg, Mn, Cu, and Zn were significantly less in US cells compared to that in NS cells (p < 0.05 or 0.01. Pre-treatment with TPEN increased simvastatin-induced cytotoxicity and eliminated the distinction between both cells of simvastatin-induced cytotoxicity. These results suggest that Zn deficiencies may be involved in the increased risk for muscle complaints in ESKD patients. In conclusion, the increased severity of statin-induced rhabdomyolysis in ESKD patients may be partly due to trace elements deficiencies.

  15. Effects of dietary inulin, statin, and their co-treatment on hyperlipidemia, hepatic steatosis and changes in drug-metabolizing enzymes in rats fed a high-fat and high-sucrose diet

    Sugatani Junko

    2012-03-01

    Full Text Available Abstract Background Rats fed a high-fat and high-sucrose (HF diet develop hepatic steatosis and hyperlipidemia. There are several reports that a change in nutritional status affects hepatic levels of drug-metabolizing enzymes. Synthetic inulin is a dietary component that completely evades glucide digestion. Supplementing a HF diet with inulin ameliorates hypertriglycemia and hepatic steatosis, but not hypercholesterolemia. This study aimed at distinguishing the effects of synthetic inulin and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin, which inhibit cholesterol biosynthesis. Methods We examined effects of co-treatment with synthetic inulin (5% and fluvastatin (0, 4, and 8 mg/kg, per os on body weight, epidydimal white adipose tissue weight, serum and hepatic lipid profiles, and hepatic cytochrome P450 (CYP mRNA and protein profiles in rats fed a standard diet or a HF diet for 3 weeks. Results Treatment with the synthetic inulin (5% or fluvastatin at 4 mg/kg (lethal dose in rats fed the HF diet, 8 mg/kg ameliorated the elevation in hepatic triacylglycerol and total cholesterol levels in rats fed the HF diet. Whereas co-treatment with the inulin (5% and fluvastatin (4 mg/kg had a tendency to more strongly suppress the elevation in serum levels of very low density lipoprotein triacylglycerol than either treatment alone, no additive or synergistic effect was found in decrease in hepatic lipid levels. Hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein and methoxyresorufin O-demethylase and ethoxyresorufin O-deethylase activities were reduced in rats fed the HF diet. The synthetic inulin alleviated the reduction in hepatic levels of CYP1A1/2 and CYP2E1 mRNA and protein more strongly than fluvastatin, and no synergistic effects were observed on co-treatment. Furthermore, hepatic levels of aryl hydrocarbon receptor mRNA were decreased in rats fed the HF diet and recovered to near normal values with the intake of dietary inulin

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

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

    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.

  18. Prevalence of dyslipidaemia in statin-treated patients in Ireland: Irish results of the DYSlipidaemia International Study (DYSIS).

    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.

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

    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

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

    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.

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

    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.

  2. Toward "pain-free" statin prescribing: clinical algorithm for diagnosis and management of myalgia.

    Jacobson, Terry A

    2008-06-01

    Myalgia, which often manifests as pain or soreness in skeletal muscles, is among the most salient adverse events associated with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins). Clinical issues related to statin-associated myotoxicity include (1) incidence in randomized controlled trials and occurrence in postmarketing surveillance databases; (2) potential differences between statins in their associations with such adverse events; and (3) diagnostic and treatment strategies to prevent, recognize, and manage these events. Data from systematic reviews, meta-analyses, clinical and observational trials, and post-marketing surveillance indicate that statin-associated myalgia typically affects approximately 5.0% of patients, as myopathy in 0.1% and as rhabdomyolysis in 0.01%. However, studies also suggest that myalgia is among the leading reasons patients discontinue statins (particularly high-dose statin monotherapy) and that treatment with certain statins (eg, fluvastatin) is unlikely to result in such adverse events. This review presents a clinical algorithm for monitoring and managing statin-associated myotoxicity. The algorithm highlights risk factors for muscle toxicity and provides recommendations for (1) creatine kinase measurements and monitoring; (2) statin dosage reduction, discontinuation, and rechallenge; and (3) treatment alternatives, such as extended-release fluvastatin with or without ezetimibe, low-dose or alternate-day rosuvastatin, or ezetimibe with or without colesevelam. The algorithm should help to inform and enhance patient care and reduce the risk of myalgia and other potentially treatment-limiting muscle effects that might undermine patient adherence and compromise the overall cardioprotective benefits of statins.

  3. Direct-to-consumer television advertising exposure, diagnosis with high cholesterol, and statin use.

    Niederdeppe, Jeff; Byrne, Sahara; Avery, Rosemary J; Cantor, Jonathan

    2013-07-01

    While statin drugs are recommended for secondary prevention of coronary heart disease (CHD), there is no medical consensus on whether or not a statin should be added to lifestyle change efforts for primary prevention of CHD. Previous research suggests that exposure to direct-to-consumer advertising (DTCA) increases drug demand among those at comparatively low risk. Research has yet to examine whether individual-level DTCA exposure may influence statin use among men and women at high, moderate, or low risk for future cardiac events. To determine the relationship between estimated exposure to DTCA for statin drugs and two clinical variables: diagnosis with high cholesterol and statin use. We used logistic regression to analyze repeated cross-sectional surveys of the United States population, merged with data on the frequency of DTCA appearances on national, cable, and local television, between 2001 and 2007. American adults (n=106,685) aged 18 and older. Levels of exposure to statin DTCA, based on ad appearances and TV viewing patterns; self-reports of whether or not a respondent has been diagnosed with high cholesterol, and whether or not a respondent took a statin in the past year. Adjusting for potential confounders, we estimate that exposure to statin ads increased the odds of being diagnosed with high cholesterol by 16 to 20 %, and increased statin use by 16 to 22 %, among both men and women (p<0.05). These associations were driven almost exclusively by men and women at low risk for future cardiac events. There was also evidence of a negative association between DTCA exposure and statin use among high-risk women (p<0.05) CONCLUSIONS: This study provides new evidence that DTCA may promote over-diagnosis of high cholesterol and over-treatment for populations where risks of statin use may outweigh potential benefits.

  4. Statin precipitated lactic acidosis?

    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).

  5. Statin use and Parkinson's disease in 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...

  6. Mass media and GP statin prescribing.

    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

  7. Statins are related to impaired exercise capacity in males but not females.

    Bahls, Martin; Groß, Stefan; Ittermann, Till; Busch, Raila; Gläser, Sven; Ewert, Ralf; Völzke, Henry; Felix, Stephan B; Dörr, Marcus

    2017-01-01

    Exercise and statins reduce cardiovascular disease (CVD). Exercise capacity may be assessed using cardiopulmonary exercise testing (CPET). Whether statin medication is associated with CPET parameters is unclear. We investigated if statins are related with exercise capacity during CPET in the general population. Cross-sectional data of two independent cohorts of the Study of Health in Pomerania (SHIP) were merged (n = 3,500; 50% males). Oxygen consumption (VO2) at peak exercise (VO2peak) and anaerobic threshold (VO2@AT) was assessed during symptom-limited CPET. Two linear regression models related VO2peak with statin usage were calculated. Model 1 adjusted for age, sex, previous myocardial infarction, and physical inactivity and model 2 additionally for body mass index, smoking, hypertension, diabetes and estimated glomerular filtration rate. Propensity score matching was used for validation. Statin usage was associated with lower VO2peak (no statin: 2336; 95%-confidence interval [CI]: 2287-2,385 vs. statin 2090; 95%-CI: 2,031-2149 ml/min; P exercise capacity in males but not females. Sex specific effects of statins on cardiopulmonary exercise capacity deserve further research.

  8. Prevalence of Potential and Clinically Relevant Statin-Drug Interactions in Frail and Robust Older Inpatients.

    Thai, Michele; Hilmer, Sarah; Pearson, Sallie-Anne; Reeve, Emily; Gnjidic, Danijela

    2015-10-01

    A significant proportion of older people are prescribed statins and are also exposed to polypharmacy, placing them at increased risk of statin-drug interactions. To describe the prevalence rates of potential and clinically relevant statin-drug interactions in older inpatients according to frailty status. A cross-sectional study of patients aged ≥65 years who were prescribed a statin and were admitted to a teaching hospital between 30 July and 10 October 2014 in Sydney, Australia, was conducted. Data on socio-demographics, comorbidities and medications were collected using a standardized questionnaire. Potential statin-drug interactions were defined if listed in the Australian Medicines Handbook and three international drug information sources: the British National Formulary, Drug Interaction Facts and Drug-Reax(®). Clinically relevant statin-drug interactions were defined as interactions with the highest severity rating in at least two of the three international drug information sources. Frailty was assessed using the Reported Edmonton Frail Scale. A total of 180 participants were recruited (median age 78 years, interquartile range 14), 35.0% frail and 65.0% robust. Potential statin-drug interactions were identified in 10% of participants, 12.7% of frail participants and 8.5% of robust participants. Clinically relevant statin-drug interactions were identified in 7.8% of participants, 9.5% of frail participants and 6.8% of robust participants. Depending on the drug information source used, the prevalence rates of potential and clinically relevant statin-drug interactions ranged between 14.4 and 35.6% and between 14.4 and 20.6%, respectively. In our study of frail and robust older inpatients taking statins, the overall prevalence of potential statin-drug interactions was low and varied significantly according to the drug information source used.

  9. Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics

    Ronaldo Altenburg Gismondi

    2015-01-01

    Full Text Available AbstractBackground:Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness.Objective:To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness.Methods:Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring, endothelial function (brachial artery flow-mediated dilation, and vascular stiffness (pulse wave velocity were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively.Results:The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007, and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003 when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820. There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586.Conclusion:Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

  10. The utility of observational studies in clinical decision making: lessons learned from statin trials.

    Foody, JoAnne M; Mendys, Phillip M; Liu, Larry Z; Simpson, Ross J

    2010-05-01

    Contemporary clinical decision making is well supported by a wide variety of information sources, including clinical practice guidelines, position papers, and insights from randomized controlled trials (RCTs). Much of our fundamental understanding of cardiovascular risk factors is based on multiple observations from major epidemiologic studies, such as The Seven Country Studies and the US-based Framingham Heart Study. These studies provided the framework for the development of clinical practice guidelines, including the National Cholesterol Education Program Adult Treatment Panel series. The objective of this article is to highlight the value of observational studies as a complement to clinical trial data for clinical decision making in real-world practice. Although RCTs are still the benchmark for assessing clinical efficacy and safety of a specific therapeutic approach, they may be of limited utility to practitioners who must then adapt the lessons learned from the trial into the patient care environment. The use of well-structured observational studies can improve our understanding of the translation of clinical trials into clinical practice, as demonstrated here with the example of statins. Although such studies have their own limitations, improved techniques for design and analysis have reduced the impact of bias and confounders. The introduction of the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines has provided more uniformity for such studies. When used together with RCTs, observational studies can enhance our understanding of effectiveness and utility in real-world clinical practice. In the examples of statin observational studies, the results suggest that relative effectiveness of different statins and potential impact of switching statins should be carefully considered in treating individual patients by practicing physicians.

  11. Use of statins and risk of glioma

    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....

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

    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

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

    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.

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

    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

  15. Assessment and Treatment of Paraphilias.

    Seligman, Linda; Hardenburg, Stephanie A.

    2000-01-01

    Provides a description of the category of mental disorders called "paraphilias" and guidelines for assessment of people who present with paraphillic behavior. Includes a review of inventories that can facilitate diagnosis and description of paraphilias. Discusses effective approaches to treatment of these disorders as well as personal and…

  16. Clinical review: impact of statin substitution policies on patient outcomes

    Atar, Dan; Carmena, Rafael; Clemmensen, Peter; K-Laflamme, Annik; Wassmann, Sven; Lansberg, Peter; Hobbs, Richard

    2009-01-01

    The increasing awareness of cost issues in health care has led to the increasing use of policy-driven substitution of branded for generic medications, particularly relative to statin treatment for cardiovascular diseases. While there are potential short-term health care savings, the consequences for

  17. Clinical review: impact of statin substitution policies on patient outcomes

    Atar, Dan; Carmena, Rafael; Clemmensen, Peter

    2009-01-01

    BACKGROUND: The increasing awareness of cost issues in health care has led to the increasing use of policy-driven substitution of branded for generic medications, particularly relative to statin treatment for cardiovascular diseases. While there are potential short-term health care savings...

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

    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...

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

    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.

  20. Plasma apolipoprotein M responses to statin and fibrate administration in type 2 diabetes mellitus

    Kappelle, Paul J W H; Ahnström, Josefin; Dikkeschei, Bert D

    2010-01-01

    by statin or fibrate administration in patients with diabetes mellitus. Methods: Fourteen type 2 diabetic patients participated in a placebo-controlled crossover study which included three 8-week treatment periods with simvastatin (40mg daily), bezafibrate (400mg daily), and their combination. Results: Apo.......02 to P treatment periods. Conclusions: This study suggests that, even though plasma apoM is lowered by statins, apoM metabolism is to a considerable extent independent of statin- and fibrate-affected pathways involved in cholesterol...

  1. Does Googling lead to statin intolerance?

    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.

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

    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

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

    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.

  4. Statin use and all-cause and cancer mortality: BioBank Japan cohort

    Hiroshi Yokomichi

    2017-03-01

    Full Text Available Background: Statins are the first-line agents used to treat patients with high serum low-density lipoprotein cholesterol levels, thus reducing the risk of death from arterial sclerotic cardiovascular disease; however, little is known about the effects of non-statin pharmacological interventions on mortality as well as about the potential protective effects of statin use against cancer death. This work aimed to compare all-cause and cancer mortality among patients with hyperlipidaemia who did and did not receive statin treatment. Methods: Between 2003 and 2007 fiscal years, we recruited Japanese patients diagnosed with hyperlipidaemia from 66 hospitals. Patients in our cohort were followed up for a maximum of 12 years to observe the causes of death. Kaplan–Meier estimates from the baseline were used to compare the mortality of patients based on the administered medicine. All-cause mortality were compared among patients with/without administration of statins and other agents; any-organ and colorectal cancer mortality were compared between patients with/without administration of statins. Results: Our cohort included 41,930 patients with mean ages of 64–66 years and mean body mass indices of 24–25 kg/m2. Patients who received statin monotherapy and were treated with lifestyle modification exhibited nearly identical survival curves, whereas statin use represented a non-significant but potentially protective effect against colorectal cancer-related mortality. The lowest mortality in this cohort was associated with resin monotherapy. Conclusions: Mortality rate has been similar for patients treated with statin monotherapy and lifestyle modification. Statin monotherapy could potentially reduce any-organ- and colorectal cancer-related mortality.

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

    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. Association of Continuity of Primary Care and Statin Adherence.

    James R Warren

    Full Text Available Deficiencies in medication adherence are a major barrier to effectiveness of chronic condition management. Continuity of primary care may promote adherence. We assessed the association of continuity of primary care with adherence to long-term medication as exemplified by statins.We linked data from a prospective study of 267,091 Australians aged 45 years and over to national data sets on prescription reimbursements, general practice claims, hospitalisations and deaths. For participants having a statin dispense within 90 days of study entry, we computed medication possession ratio (MPR and usual provider continuity index (UPI for the subsequent two years. We used multivariate Poisson regression to calculate the relative risk (RR and 95% confidence interval (CI for the association between tertiles of UPI and MPR adjusted for socio-demographic and health-related patient factors, including age, gender, remoteness of residence, smoking, alcohol intake, fruit and vegetable intake, physical activity, prior heart disease and speaking a language other than English at home. We performed a comparison approach using propensity score matching on a subset of the sample.36,144 participants were eligible and included in the analysis among whom 58% had UPI greater than 75%. UPI was significantly associated with 5% increased MPR for statin adherence (95% CI 1.04-1.06 for highest versus lowest tertile. Dichotomised analysis using a cut-off of UPI at 75% showed a similar effect size. The association between UPI and statin adherence was independent of socio-demographic and health-related factors. Stratification analyses further showed a stronger association among those who were new to statins (RR 1.33, 95% CI 1.15-1.54.Greater continuity of care has a positive association with medication adherence for statins which is independent of socio-demographic and health-related factors.

  7. Association of Continuity of Primary Care and Statin Adherence.

    Warren, James R; Falster, Michael O; Tran, Bich; Jorm, Louisa

    2015-01-01

    Deficiencies in medication adherence are a major barrier to effectiveness of chronic condition management. Continuity of primary care may promote adherence. We assessed the association of continuity of primary care with adherence to long-term medication as exemplified by statins. We linked data from a prospective study of 267,091 Australians aged 45 years and over to national data sets on prescription reimbursements, general practice claims, hospitalisations and deaths. For participants having a statin dispense within 90 days of study entry, we computed medication possession ratio (MPR) and usual provider continuity index (UPI) for the subsequent two years. We used multivariate Poisson regression to calculate the relative risk (RR) and 95% confidence interval (CI) for the association between tertiles of UPI and MPR adjusted for socio-demographic and health-related patient factors, including age, gender, remoteness of residence, smoking, alcohol intake, fruit and vegetable intake, physical activity, prior heart disease and speaking a language other than English at home. We performed a comparison approach using propensity score matching on a subset of the sample. 36,144 participants were eligible and included in the analysis among whom 58% had UPI greater than 75%. UPI was significantly associated with 5% increased MPR for statin adherence (95% CI 1.04-1.06) for highest versus lowest tertile. Dichotomised analysis using a cut-off of UPI at 75% showed a similar effect size. The association between UPI and statin adherence was independent of socio-demographic and health-related factors. Stratification analyses further showed a stronger association among those who were new to statins (RR 1.33, 95% CI 1.15-1.54). Greater continuity of care has a positive association with medication adherence for statins which is independent of socio-demographic and health-related factors.

  8. Vitamin D status modifies the association between statin use and musculoskeletal pain: a population based study.

    Morioka, Travis Y; Lee, Alice J; Bertisch, Suzanne; Buettner, Catherine

    2015-01-01

    Past studies examining the effect of vitamin D on statin myalgia have been variable; however, these studies were done in limited samples not representative of the general population. We aimed to evaluate whether vitamin D status modifies the association between statin use and musculoskeletal pain in a sample representative of the general population. We conducted a cross-sectional study using the National Health and Nutrition Examination Survey 2001-2004. Musculoskeletal symptoms and statin use were self-reported. Vitamin D status was assessed using serum 25 hydroxyvitamin D (25[OH]D), categorized as statin use and prevalent musculoskeletal pain, we performed multivariable-adjusted logistic regression models stratified by 25(OH)D status. Among 5907 participants ≥40 years old, mean serum 25(OH)D was 23.6 ng/mL (95% CI, 22.9-24.3). In stratified multivariable-adjusted logistic regression models, individuals with 25(OH)D statin had a significantly higher odds of musculoskeletal pain compared to those not using a statin (adjusted odds ratio [aOR], 1.90; 95% CI, 1.18-3.05). Among those with 25(OH)D ≥15 ng/mL, we found no significant association between statin use and musculoskeletal pain (aOR, 0.91; 95% CI, 0.71-1.16). Among adults ≥ 40 years old with 25(OH)D statin users had nearly 2 times greater odds of reporting musculoskeletal pain compared to non-statin users. Our findings support the hypothesis that vitamin D deficiency modifies the risk of musculoskeletal symptoms experienced with statin use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    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.

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

    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.

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

    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.

  12. Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells

    Vanova, K.; Boukalova, S.; Gbelcova, H.; Muchova, L.; Neuzil, J.; Gurlich, R.; Ruml, T.; Vitek, L.

    2016-01-01

    Pancreatic cancer is recognized as one of the most fatal tumors due to its aggressiveness and resistance to therapy. Statins were previously shown to inhibit the proliferation of cancer cells via various signaling pathways. In healthy tissues, statins activate the heme oxygenase pathway, nevertheless the role of heme oxygenase in pancreatic cancer is still controversial. The aim of this study was to evaluate, whether anti-proliferative effects of statins in pancreatic cancer cells are mediated via the heme oxygenase pathway. In vitro effects of various statins and hemin, a heme oxygenase inducer, on cell proliferation were evaluated in PA-TU-8902, MiaPaCa-2 and BxPC-3 human pancreatic cancer cell lines. The effect of statins on heme oxygenase activity was assessed and heme oxygenase-silenced cells were used for pancreatic cancer cell proliferation studies. Cell death rate and reactive oxygen species production were measured in PA-TU-8902 cells, followed by evaluation of the effect of cerivastatin on GFP-K-Ras trafficking and expression of markers of invasiveness, osteopontin (SPP1) and SOX2. While simvastatin and cerivastatin displayed major anti-proliferative properties in all cell lines tested, pravastatin did not affect the cell growth at all. Strong anti-proliferative effect was observed also for hemin. Co-treatment of cerivastatin and hemin increased anti-proliferative potential of these agents, via increased production of reactive oxygen species and cell death compared to individual treatment. Heme oxygenase silencing did not prevent pancreatic cancer cells from the tumor-suppressive effect of cerivastatin or hemin. Cerivastatin, but not pravastatin, protected Ras protein from trafficking to the cell membrane and significantly reduced expressions of SPP1 (p < 0.05) and SOX2 (p < 0.01). Anti-proliferative effects of statins and hemin on human pancreatic cancer cell lines do not seem to be related to the heme oxygenase pathway. While hemin triggers reactive

  13. Cardiovascular Risk and Statin Eligibility of Young Adults After an MI: Partners YOUNG-MI Registry.

    Singh, Avinainder; Collins, Bradley L; Gupta, Ankur; Fatima, Amber; Qamar, Arman; Biery, David; Baez, Julio; Cawley, Mary; Klein, Josh; Hainer, Jon; Plutzky, Jorge; Cannon, Christopher P; Nasir, Khurram; Di Carli, Marcelo F; Bhatt, Deepak L; Blankstein, Ron

    2018-01-23

    Despite significant progress in primary prevention, the rate of MI has not declined in young adults. The purpose of this study was to evaluate statin eligibility based on the 2013 American College of Cardiology/American Heart Association guidelines for treatment of blood cholesterol and 2016 U.S. Preventive Services Task Force recommendations for statin use in primary prevention in a cohort of adults who experienced a first-time myocardial infarction (MI) at a young age. The YOUNG-MI registry is a retrospective cohort from 2 large academic centers, which includes patients who experienced an MI at age ≤50 years. Diagnosis of type 1 MI was adjudicated by study physicians. Pooled cohort risk equations were used to estimate atherosclerotic cardiovascular disease risk score based on data available prior to MI or at the time of presentation. Of 1,685 patients meeting inclusion criteria, 210 (12.5%) were on statin therapy prior to MI and were excluded. Among the remaining 1,475 individuals, the median age was 45 years, there were 294 (20%) women, and 846 (57%) had ST-segment elevation MI. At least 1 cardiovascular risk factor was present in 1,225 (83%) patients. The median 10-year atherosclerotic cardiovascular disease risk score of the cohort was 4.8% (interquartile range: 2.8% to 8.0%). Only 724 (49%) and 430 (29%) would have met criteria for statin eligibility per the 2013 American College of Cardiology/American Heart Association guidelines and 2016 U.S. Preventive Services Task Force recommendations, respectively. This finding was even more pronounced in women, in whom 184 (63%) were not eligible for statins by either guideline, compared with 549 (46%) men (p adults who present with an MI at a young age would not have met current guideline-based treatment thresholds for statin therapy prior to their MI. These findings highlight the need for better risk assessment tools among young adults. Copyright © 2018 American College of Cardiology Foundation. Published by

  14. Statin intolerance - a question of definition.

    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.

  15. Heterologous expression of MlcE in Saccharomyces cerevisiae provides resistance to natural and semi-synthetic statins

    Ana Ley

    2015-12-01

    Full Text Available Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key enzyme in cholesterol biosynthesis. Their extensive use in treatment and prevention of cardiovascular diseases placed statins among the best selling drugs. Construction of Saccharomyces cerevisiae cell factory for the production of high concentrations of natural statins will require establishment of a non-destructive self-resistance mechanism to overcome the undesirable growth inhibition effects of statins. To establish active export of statins from yeast, and thereby detoxification, we integrated a putative efflux pump-encoding gene mlcE from the mevastatin-producing Penicillium citrinum into the S. cerevisiae genome. The resulting strain showed increased resistance to both natural statins (mevastatin and lovastatin and semi-synthetic statin (simvastatin when compared to the wild type strain. Expression of RFP-tagged mlcE showed that MlcE is localized to the yeast plasma and vacuolar membranes. We provide a possible engineering strategy for improvement of future yeast based production of natural and semi-synthetic statins. Keywords: Polyketide, Statins, Saccharomyces cerevisiae, Transport, Cell factory, Resistance

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

    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.

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

    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.

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

    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

  19. Pleiotropic effects of statins in distal human pulmonary artery smooth muscle cells

    Butrous Ghazwan S

    2011-10-01

    Full Text Available Abstract Background Recent clinical data suggest statins have transient but significant effects in patients with pulmonary arterial hypertension. In this study we explored the molecular effects of statins on distal human pulmonary artery smooth muscle cells (PASMCs and their relevance to proliferation and apoptosis in pulmonary arterial hypertension. Methods Primary distal human PASMCs from patients and controls were treated with lipophilic (simvastatin, atorvastatin, mevastatin and fluvastatin, lipophobic (pravastatin and nitric-oxide releasing statins and studied in terms of their DNA synthesis, proliferation, apoptosis, matrix metalloproteinase-9 and endothelin-1 release. Results Treatment of human PASMCs with selected statins inhibited DNA synthesis, proliferation and matrix metalloproteinase-9 production in a concentration-dependent manner. Statins differed in their effectiveness, the rank order of anti-mitogenic potency being simvastatin > atorvastatin > > pravastatin. Nevertheless, a novel nitric oxide-releasing derivative of pravastatin (NCX 6550 was effective. Lipophilic statins, such as simvastatin, also enhanced the anti-proliferative effects of iloprost and sildenafil, promoted apoptosis and inhibited the release of the mitogen and survival factor endothelin-1. These effects were reversed by mevalonate and the isoprenoid intermediate geranylgeranylpyrophosphate and were mimicked by inhibitors of the Rho and Rho-kinase. Conclusions Lipophilic statins exert direct effects on distal human PASMCs and are likely to involve inhibition of Rho GTPase signalling. These findings compliment some of the recently documented effects in patients with pulmonary arterial hypertension.

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

    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.

  1. Lipid-lowering effects of statins

    Ramos-Esquivel, Allan; Leon-Cespedes, Carlos

    2007-01-01

    Statins have become one of the most prescribed drugs in the world. These medications are used in the treatment of dyslipidemia and in the prevention of cardiovascular diseases. Recently, new evidence has emerged about their mechanisms of action and their pleiotropic properties, well beyond lowering cholesterol levels. This pharmacodynamic action has called the attention of many investigators who suggest their use in several diseases centered on inflammation, immune disorders and cell proliferation. Although there is wide evidence that recognizes their efficacy in several disease models, there is still a lack of studies to approve their use in clinical practice. The pharmacodynamic properties focusing on the pathophysiology that suggests their clinical use in the treatment of several diseases have been reviewed. (author) [es

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

    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. Statin Safety in Chinese: A Population-Based Study of Older Adults.

    Li, Daniel Q; Kim, Richard B; McArthur, Eric; Fleet, Jamie L; Hegele, Robert A; Shah, Baiju R; Weir, Matthew A; Molnar, Amber O; Dixon, Stephanie; Tu, Jack V; Anand, Sonia; Garg, Amit X

    2016-01-01

    Compared to Caucasians, Chinese achieve a higher blood concentration of statin for a given dose. It remains unknown whether this translates to increased risk of serious statin-associated adverse events amongst Chinese patients. We conducted a population-based retrospective cohort study of older adults (mean age, 74 years) newly prescribed a statin in Ontario, Canada between 2002 and 2013, where 19,033 Chinese (assessed through a validated surname algorithm) were matched (1:3) by propensity score to 57,099 non-Chinese. This study used linked healthcare databases. The follow-up observation period (mean 1.1, maximum 10.8 years) was similar between groups, as were the reasons for censoring the observation period (end of follow-up, death, or statin discontinuation). Forty-seven percent (47%) of Chinese were initiated on a higher than recommended statin dose. Compared to non-Chinese, Chinese ethnicity did not associate with any of the four serious statin-associated adverse events assessed in this study [rhabdomyolysis hazard ratio (HR) 0.61 (95% CI 0.28 to 1.34), incident diabetes HR 1.02 (95% CI 0.80 to 1.30), acute kidney injury HR 0.90 (95% CI 0.72 to 1.13), or all-cause mortality HR 0.88 (95% CI 0.74 to 1.05)]. Similar results were observed in subgroups defined by statin type and dose. We observed no higher risk of serious statin toxicity in Chinese than matched non-Chinese older adults with similar indicators of baseline health. Regulatory agencies should review available data, including findings from our study, to decide if a change in their statin dosing recommendations for people of Chinese ethnicity is warranted.

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

    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

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

    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.

  6. Lipid-lowering drugs (statins) and peripheral neuropathy.

    Emad, Mohammadreza; Arjmand, Hosein; Farpour, Hamid Reza; Kardeh, Bahareh

    2018-03-01

    Peripheral neuropathy is a disorder with often unknown causes. Some drugs, including statins, are proposed to be among the causes of peripheral neuropathy. This study aimed at evaluating this condition by electrodiagnostic study among patients who had received statins. This case-control study was conducted in Shiraz, Iran in 2015, and included 39 patients aged 35-55 who had received statins for at least 6 months, and 39 healthy matched controls. Using electrodiagnosis, the sensory and motor wave features (amplitude, latency and nerve conduction velocity) of the peripheral nerves (Median, Ulnar, Tibial, Sural, and Peroneal) were evaluated among the subjects. Data were analyzed using SPSS software and pneuropathy, there were no significant differences in any of the definitions presented for peripheral neuropathy. However, the difference was close to significance for one definition [2 abnormalities in 2 nerves (p=0.055)]. Regarding mean values of the features, significant differences were observed in two features: amplitude of the peroneal motor nerve (p=0.048) and amplitude of the sural sensory nerve (p=0.036). Since statins are widely used, awareness regarding their side-effects would lead to better treatment. Even though no significant differences were found between the groups regarding the occurrence of peripheral neuropathy, there were significant differences in amplitudes of the sural sensory response and the peroneal motor response. This indicates the involvement of peripheral nerves. Therefore, we recommend that patients and physicians should be informed about the possible symptoms of this condition.

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

    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...

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

    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

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

    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.

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

    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.

  11. Statins Decrease Oxidative Stress and ICD Therapies

    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.

  12. Statins and transcriptional regulation: The FXR connection

    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

  13. Effects of HMG-CoA Reductase Inhibitors (Statins On Bone Mineral Density and Metabolism

    Nehir Samancı

    2004-06-01

    Full Text Available Hydroxy methylglutaryl coenzyme A reductase inhibitors (statins have been shown to have effects on bone metabolism in laboratory studies. While early clinic studies have showed lower risk for osteoporotic fractures among statin users than nonusers, subsequent studies have found mixed results. The purpose of this study was to investigate the effects of statins on bone mineral density (BMD and bone metabolism. Thirty-five consecutive postmenopausal hypercholesterolemic women who were treated for at least last 6 months with statins were included in the study. Seventy-five normocholesterolemic age-matched postmenopausal women were in the control group. Subjects with a history of any diseases and used drugs that may affect calcium or bone metabolism were excluded from the study. Age, associated illness, years since menopause, and body mass index (BMI were obtained from all the patients including the control group. Besides, serum calcium, phosphate, alkaline phosphates, parathyroid hormone, 25 hydroxy D3, osteocalcin, and urinary calcium excretion were measured. BMD was measured by using dual-energy x-ray absorptiometry (DEXA at femoral neck and 3rd lomber spine. Mean duration of statin use was 28.17±21.17 months. BMI was found to be statistically higher in statin users than nonusers (27.47±3.67kg/m2 and 25.46±3.91 kg/m2, respectively. The markers of bone metabolism used in the study were found to be similar between the groups. BMD was not different in statin users and nonusers at femoral neck and lomber spine. As conclusion, statin use did not affect BMD and bone metabolism in this study. In our opinion large randomised, controlled, prospective clinical trials are needed to accurately determine the role of statins in the treatment of osteoporosis.

  14. Increasing incidence of statin prescribing for the elderly without previous cardiovascular conditions:  A nation wide register study

    Kildemoes, Helle Wallach; Andersen, Morten

    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 for the increasing...... Danish statin utilization during 1996-2005, applying treatment incidence as a measure of changing prescribing behaviour Methods From three nationwide registers, we retrieved individual records on demographics, dispensed prescription drugs and hospital discharges. Danish inhabitants were followed...... for seven cardiovascular conditions, corresponding to a hierarchy of statin indications. Poisson regression analyses were applied to quantify the incidence growth, according to age and indication.  Results Treatment incidence increased from 4/1000 person years in 2000 to 17/1000 in 2005, the increase being...

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

    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 ...

  16. The Treatment Effectiveness Assessment (TEA

    Ling W

    2013-09-01

    Full Text Available Walter Ling,1 David Farabee,1 Dagmar Liepa,2 Li-Tzy Wu3 1Integrated Substance Abuse Programs, University of California, Los Angeles, CA, 2Valley Care Medical Center, Panorama City, CA, 3Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University Medical Center, Durham, NC, USA We have been surprised and gratified by the readers’ responses to our article, The Treatment Effectiveness Assessment (TEA: an efficient, patient-centered instrument for evaluating progress in recovery from addiction, which was published in December 2012.1 In the six months since that time, we have received numerous questions and observations about the article, and about the TEA instrument. Respondents were clinicians: physicians, counselors, therapists, nurses; as well as administrators and policy makers.  View original paper by Ling W, Farabee D, Liepa D, Wu LT. 

  17. Can statins improve outcome in colorectal surgery?: Part I

    Júlio César M Santos Jr

    2012-09-01

    Full Text Available Statins are recommended for people who have high serum cholesterol, and this role of statins has been well documented. However, some activities of statins, independent of their lipid-lowering effect, in conditions such as systemic inflammatory response syndrome, nephropathy, and other anti-inflammatory activities that reduce proinflammatory cytokines, are called "pleiotropic" effects of statins. For this reason, many candidates for surgical treatment are users of statins. As a result, benefits are observed in these patients, such as minimized postoperative complications, especially in cardiac or coronary surgery. This study was designed with the purpose of determining the current status of the use of statins as an adjuvant in the prevention of postoperative complications in colorectal surgery. Ongoing studies and future researches will help clarify the potential impact of statins on the prophylaxis of postoperative complications.As estatinas são drogas com o poder de inibir a hidroxi-metil-glutaril coenzima A redutase (HMG-CoA redutase, enzima que age na ativação da cadeia metabólica do colesterol. Portanto, sua principal ação, entre outros efeitos, é diminuir a concentração sérica total desse lipídeo. Por essa razão, muitas pessoas candidatas ao tratamento cirúrgico são pacientes usuários das estatinas. Seus outros efeitos, independente de sua capacidade para baixar os lipídeos circulantes, são denominados "efeitos pleiotrópicos" e estão, principalmente, relacionados à ação de bloqueio das atividades pró-inflamatórias, sobretudo minimizando, nos cardiopatas ou coronariopatas submetidos às operações cardíacas ou coronarianas, a prevalência da síndrome da reação inflamatória sistêmica, inclusive quando desencadeada por infecção. Estudos recentes têm sido elaborados para maiores conhecimentos dos mecanismos de ação das estatinas, especialmente em pacientes cardiopatas submetidos a tratamentos cirúrgicos n

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

    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.

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

    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

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

    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.

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

    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.

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

    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.

  3. Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis.

    Elham Khanicheh

    Full Text Available BACKGROUND/OBJECTIVES: Inflammatory changes on the endothelium are responsible for leukocyte recruitment to plaques in atherosclerosis. Noninvasive assessment of treatment-effects on endothelial inflammation may be of use for managing medical therapy and developing novel therapies. We hypothesized that molecular imaging of vascular cell adhesion molecule-1 (VCAM-1 with contrast enhanced ultrasound (CEU could assess treatment effects on endothelial phenotype in early atherosclerosis. METHODS: Mice with atherosclerosis produced by gene deletion of the LDL-receptor and Apobec-1-editing protein were studied. At 12 weeks of age, mice received 8 weeks of regular chow or atorvastatin-enriched chow (10 mg/kg/day. At 20 weeks, CEU molecular imaging for aortic endothelial VCAM-1 expression was performed with VCAM-1-targeted (MB(VCAM and control microbubbles (MB(Ctr. Aortic wall thickness was assessed with high frequency ultrasound. Histology, immunohistology and Western blot were used to assess plaque burden and VCAM-1 expression. RESULTS: Plaque burden was reduced on histology, and VCAM-1 was reduced on Western blot by atorvastatin, which corresponded to less endothelial expression of VCAM-1 on immunohistology. High frequency ultrasound did not detect differences in aortic wall thickness between groups. In contrast, CEU molecular imaging demonstrated selective signal enhancement for MB(VCAM in non-treated animals (MB(VCAM 2±0.3 vs MB(Ctr 0.7±0.2, p<0.01, but not in statin-treated animals (MB(VCAM 0.8±0.2 vs MB(Ctr 1.0±0.2, p = ns; p<0.01 for the effect of statin on MB(VCAM signal. CONCLUSIONS: Non-invasive CEU molecular imaging detects the effects of anti-inflammatory treatment on endothelial inflammation in early atherosclerosis. This easily accessible, low-cost technique may be useful in assessing treatment effects in preclinical research and in patients.

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

    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.

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

    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.

  6. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease

    Ingebrigtsen, Truls S; Marott, Jacob L; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: We tested the hypothesis that statin use in individuals with COPD is associated with a reduced risk of exacerbations. METHODS: We identified 5794 individuals with COPD and a measurement of C reactive protein (CRP) in the Copenhagen General Population Study (2003-2008). During 3 years...... of follow-up we recorded exacerbations with hospital admissions or oral corticosteroid treatment. In a nested case-control design, matching on age, gender, smoking, COPD severity and comorbidity, we estimated the association between statin use and exacerbations. In addition, we examined the association...... between statin use and high CRP (>3 mg/L), and the association between high CRP and exacerbations during follow-up. RESULTS: Statin use was associated with reduced odds of exacerbations in crude analysis, OR=0.68 (95% CI 0.51 to 0.91, p=0.01), as well as in multivariable conditional logistic regression...

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

    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

  8. The incidence of kidney injury for patients treated with a high-potency versus moderate-potency statin regimen after an acute coronary syndrome.

    Sarma, Amy; Cannon, Christopher P; de Lemos, James; Rouleau, Jean L; Lewis, Eldrin F; Guo, Jianping; Mega, Jessica L; Sabatine, Marc S; O'Donoghue, Michelle L

    2014-05-01

    Observational studies have raised concerns that high-potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy. PROVE IT-TIMI 22 enrolled 4162 subjects after an acute coronary syndrome (ACS) and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A-to-Z enrolled 4497 subjects after ACS and randomized them to a high-potency (simvastatin 40 mg/day × 1 months, then simvastatin 80 mg/day) versus a delayed moderate-potency statin strategy (placebo × 4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow-up. In A-to-Z, the incidence of a 1.5-fold or ≥ 0.3 mg/dL rise in serum creatinine was 11.4% for subjects randomized to a high-potency statin regimen versus 12.4% for those on a delayed moderate-potency regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.76 to 1.10; P=0.33). In PROVE IT-TIMI 22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (OR, 0.88; 95% CI, 0.71 to 1.09; P=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury-related adverse events (AEs) was not statistically different for patients on a high-potency versus moderate-potency statin regimen (OR, 1.06; 95% CI, 0.68 to 1.67; P=0.78). For patients enrolled in 2 large randomized trials of statin therapy after ACS, the use of a high-potency statin regimen did not increase the risk of kidney injury.

  9. Statin intolerance: Now a solved problem

    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.

  10. Do statins protect against upper gastrointestinal bleeding?

    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. Statin use and risk for ovarian cancer

    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....

  12. 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.

    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

  13. STATINS AND URSODEOXYCHOLIC ACID: COOPERATION OR NEUTRALITY?

    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.

  14. STATINS AND URSODEOXYCHOLIC ACID: COOPERATION OR NEUTRALITY?

    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.

  15. Statins Increase Mitochondrial and Peroxisomal Fatty Acid Oxidation in the Liver and Prevent Non-Alcoholic Steatohepatitis in Mice

    Han-Sol Park

    2016-04-01

    Full Text Available BackgroundNon-alcoholic fatty liver disease is the most common form of chronic liver disease in industrialized countries. Recent studies have highlighted the association between peroxisomal dysfunction and hepatic steatosis. Peroxisomes are intracellular organelles that contribute to several crucial metabolic processes, such as facilitation of mitochondrial fatty acid oxidation (FAO and removal of reactive oxygen species through catalase or plasmalogen synthesis. Statins are known to prevent hepatic steatosis and non-alcoholic steatohepatitis (NASH, but underlying mechanisms of this prevention are largely unknown.MethodsSeven-week-old C57BL/6J mice were given normal chow or a methionine- and choline-deficient diet (MCDD with or without various statins, fluvastatin, pravastatin, simvastatin, atorvastatin, and rosuvastatin (15 mg/kg/day, for 6 weeks. Histological lesions were analyzed by grading and staging systems of NASH. We also measured mitochondrial and peroxisomal FAO in the liver.ResultsStatin treatment prevented the development of MCDD-induced NASH. Both steatosis and inflammation or fibrosis grades were significantly improved by statins compared with MCDD-fed mice. Gene expression levels of peroxisomal proliferator-activated receptor α (PPARα were decreased by MCDD and recovered by statin treatment. MCDD-induced suppression of mitochondrial and peroxisomal FAO was restored by statins. Each statin's effect on increasing FAO and improving NASH was independent on its effect of decreasing cholesterol levels.ConclusionStatins prevented NASH and increased mitochondrial and peroxisomal FAO via induction of PPARα. The ability to increase hepatic FAO is likely the major determinant of NASH prevention by statins. Improvement of peroxisomal function by statins may contribute to the prevention of NASH.

  16. Statin use and the risk of Clostridium difficile infection: a systematic review with meta-analysis.

    Tariq, Raseen; Mukhija, Dhruvika; Gupta, Arjun; Singh, Siddharth; Pardi, Darrell S; Khanna, Sahil

    2018-01-01

    Statins have pleiotropic effects beyond cholesterol lowering by immune modulation. The association of statins with primary Clostridium difficile infection (CDI) is unclear as studies have reported conflicting findings. We performed a systematic review and meta-analysis to evaluate the association between statin use and CDI. We searched MEDLINE, Embase, and Web of Science from January 1978 to December 2016 for studies assessing the association between statin use and CDI. The Newcastle-Ottawa Scale was used to assess the methodologic quality of included studies. Weighted summary estimates were calculated using generalized inverse variance with random-effects model. Eight studies (6 case-control and 2 cohort) were included in the meta-analysis, which comprised 156,722 patients exposed to statins and 356,185 controls, with 34,849 total cases of CDI available in 7 studies. The rate of CDI in patients with statin use was 4.3%, compared with 7.8% in patients without statin use. An overall meta-analysis of 8 studies using the random-effects model demonstrated that statins may be associated with a decreased risk of CDI (maximally adjusted odds ratio [OR], 0.80; 95% CI, 0.66-0.97; P =0.02). There was significant heterogeneity among the studies, with an I 2 of 79%. No publication bias was seen. Meta-analysis of studies that adjusted for confounders revealed no protective effect of statins (adjusted OR, 0.84; 95% CI, 0.70-1.01; P =0.06, I 2 =75%). However, a meta-analysis of only full-text studies using the random-effects model demonstrated a decreased risk of CDI with the use of statins (OR 0.77; 95% CI, 0.61-0.99; P =0.04, I 2 =85%). Meta-analyses of existing studies suggest that patients prescribed a statin may be at decreased risk for CDI. The results must be interpreted with caution given the significant heterogeneity and lack of benefit on analysis of studies that adjusted for confounders.

  17. Statins and risk of diabetes mellitus

    Richard Tjan

    2015-12-01

    Full Text Available Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, which reduces HMG-CoA to mevalonate, the precursor of cholesterol via squalene. Inhibition of HMG-CoA reductase results in a decrease in cholesterol production. Since 1987, when the United States Federal Drug Administration (FDA approved lovastatin for clinical use,(1 statins have been widely used for secondary prevention of cardiovascular disease, particularly coronary heart disease (CHD, which is associated with high levels of low-density lipoprotein (LDL cholesterol. Statins are also used in type 2 diabetes mellitus, since this carries a high risk of CHD. Statins have several adverse effects, to which must now be added new onset diabetes. In 2012 the FDA issued a warning about the risk of newly developed diabetes mellitus in older persons, such that statin labels now include information on glycemic effects, including diabetes and increases in hemoglobin A1c or fasting plasma glucose.(2 According to the results of a recent meta-analysis involving 13,966 40+-year patients newly treated with statins between 1 January 1977 and 31 March 2011, a moderate but significant increase was found in the risk of new onset diabetes within the first two years of using regular higher potency statins (rosuvastatin >10 mg, atorvastatin >20 mg, and simvastatin >40 mg, compared with lower potency drugs. Therefore these investigators caution clinicians regarding the use of higher potency statins in secondary prevention of cardiovascular disease.(2 The use of a new drug carries a “built-in time-bomb”, because nothing is known about its side effects, except for those revealed by animal tests and limited clinical trials. Even a multicenter clinical trial cannot be expected to reveal all possible adverse reactions associated with a new drug. As an illustration, in patients without diabetes mellitus, more than 345 000 cases were needed to detect an increase in fasting

  18. Early Statin Use and the Progression of Alzheimer Disease: A Total Population-Based Case-Control Study.

    Lin, Feng-Cheng; Chuang, Yun-Shiuan; Hsieh, Hui-Min; Lee, Tzu-Chi; Chiu, Kuei-Fen; Liu, Ching-Kuan; Wu, Ming-Tsang

    2015-11-01

    The protective effect of statin on Alzheimer disease (AD) is still controversial, probably due to the debate about when to start the use of statin and the lack of any large-scale randomized evidence that actually supports the hypothesis. The purpose of this study was to examine the protective effect of early statin use on mild-to-moderate AD in the total Taiwanese population.This was a total population-based case-control study, using the total population of Taiwanese citizens seen in general medical practice; therefore, the findings can be applied to the general population. The study patients were those with newly diagnosed dementia (ICD-9 290.x) and prescribed any acetylcholinesterase inhibitors (AChEI) from the Taiwan National Health Insurance dataset in 1997 to 2008. The newly diagnosed eligible mild-to-moderate AD patients were traced from the dates of their index dates, which was defined as the first day to receive any AChEI treatment, back to 1 year (exposure period) to categorize them into AD with early statin use and without early statin use. Early statin use was defined as patients using statin before AChEI treatment. Alzheimer disease patients with early statin use were those receiving any statin treatment during the exposure period. Then, we used propensity-score-matched strategy to match these 2 groups as 1:1. The matched study patients were followed-up from their index dates. The primary outcome was the discontinuation of AChEI treatment, indicating AD progression.There were 719 mild-to-moderate AD-paired patients with early statin use and without early statin use for analyses. Alzheimer disease progression was statistically lower in AD patients with early statin use than those without (P = 0.00054). After adjusting for other covariates, mild-to-moderate AD patients with early stain use exhibited a 0.85-risk (95% CI = 0.76-0.95, P = 0.0066) to have AD progression than those without.Early statin use was significantly associated with a reduction in AD

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

    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.

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

    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.

  1. [Statins and ASS for primary prevention of cardiovascular and cerebrovascular disease].

    Goltz, L; Bodechtel, U; Siepmann, T

    2014-02-01

    Whereas statins and acetylsalicylic acid (ASA) are considered gold standard for secondary prevention following myocardial infarction or atherotrombotic stroke, there are inconsistent data on the use of these drugs for primary prevention in patients with increased cardiovascular risk. Some meta-analyses indicated that the use of statins and ASA for primary prevention of cardiovascular disease can reduce the risk of cardiovascular events such as ischemic stroke or myocardial infarction. However, the effects of primary prevention with statins and ASA on mortality varied in the data included in these meta-analyses. Therefore the guidelines of the German College of General Practitioners and Family Physicians recommend primary prevention with statins and ASA only in those patients who have a 10-year risk of cardiovascular events which exceeds 20 %. Divergently, primary prevention with ASA is not recommended by the European Society of Cardiology. Observational studies suggested that treatment success of primary prevention with statins and ASA depends on various factors such as adherence to medication and prescription behavior of physicians. This review summarizes the current literature on primary prevention of cardiovascular events with ASA and statins. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Outcomes from intracerebral hemorrhage among patients pre-treated with statins

    Flávio Ramalho Romero

    2011-06-01

    Full Text Available OBJECTIVE: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase inhibitors, or statins, have been associated with improved clinical outcomes after ischemic stroke and subarachnoid hemorrhage, but with an increased risk of incidental spontaneous intracerebral hemorrhage (ICH. We investigated whether the statin use before ICH, was associated with functional independence, 90 days after treatment. METHOD: We analyzed 124 consecutive ICH patients with 90-day outcome data who were enrolled in a prospective cohort study between 2006 and 2009. Eighty-three patients were included in this study. Among ICH survivors, univariate Cox regression models and Kaplan-Meier plots were used to determine subject characteristics that were associated with an increased risk of recurrence. Statin usage was determined through interviewing the patient at the time of ICH and confirmed by reviewing their medical records. Independent status was defined as Glasgow Outcome Scale grades 4 or 5. RESULTS: Statins were used by 20 out of 83 patients (24% before ICH onset. There was no effect from pre-ICH statin use on functional independence rates (28% versus 29%, P=0.84 or mortality (46% versus 45%, P=0.93. CONCLUSION: Pre-ICH statin use is not associated with changes to ICH functional outcome or mortality.

  3. Statins Activate Human PPAR Promoter and Increase PPAR mRNA Expression and Activation in HepG2 Cells

    Makoto Seo

    2008-01-01

    Full Text Available Statins increase peroxisome proliferator-activated receptor (PPAR mRNA expression, but the mechanism of this increased PPAR production remains elusive. To examine the regulation of PPAR production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin on human PPAR promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1 Majority of statins enhanced PPAR promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPAR promoter. This enhancement may be mediated by statin-induced HNF-4. (2 PPAR mRNA expression was increased by statin treatment. (3 The PPAR levels in nuclear fractions were increased by statin treatment. (4 Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPAR/RXR expression vectors. In summary, these data demonstrate that PPAR production and activation are upregulated through the PPAR promoter activity by statin treatment.

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

    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.

  5. Statins use and risk of depression: a systematic review and meta-analysis.

    Parsaik, Ajay K; Singh, Balwinder; Murad, M Hassan; Singh, Kuljit; Mascarenhas, Soniya S; Williams, Mark D; Lapid, Maria I; Richardson, Jarrett W; West, Colin P; Rummans, Teresa A

    2014-05-01

    Statin use has been associated with depression; however studies of the association between statin use and depression have yielded mixed results. To determine whether statin use is associated with depression and to evaluate the evidence supporting this association. Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched through December 28, 2012. We included studies that evaluated exposure to statins, reported the development of depression, and relative risks or odds ratios (ORs) or provided data for their estimation. Two reviewers screened 981 abstracts independently using a standardized form, reviewed full text of 59 selected articles, and included 7 studies in this metaanalysis. Study design, statin exposure, development of depression, and study quality were extracted by 2 independent reviewers. A pooled OR with 95% confidence interval (CI) was estimated using the random-effects model and heterogeneity was assessed using Cochran's Q test and the I(2) statistic. Seven observational studies (4 cohort, 2 nested case-control, and 1 cross-sectional) from 5 countries enrolling 9187 patients were included. Statin users were 32% less likely to develop depression than nonusers (adjusted OR, 0.68; 95% CI, 0.52-0.89). Modest heterogeneity was observed between the studies (I(2)=55%, P=0.01), which could be accounted for by one study, exclusion of which removed the heterogeneity (P=0.40, I(2)=2%) and further strengthened the antidepressant effect of statin (adjusted OR, 0.63; 95% CI, 0.43-0.93). Heterogeneity could not be explained by study design or study population. The quality of supporting evidence was fair. This systematic review and meta-analysis suggests that statin use is associated with lower risk for depression. However, higher-quality studies are needed to confirm the magnitude of this association. Copyright © 2013

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

    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.

  7. Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans.

    Hendrie, Hugh C; Hake, Ann; Lane, Kathleen; Purnell, Christianna; Unverzagt, Frederick; Smith-Gamble, Valerie; Murrell, Jill; Ogunniyi, Adesola; Baiyewu, Olusegun; Callahan, Chris; Saykin, Andrew; Taylor, Stanley; Hall, Kathleen; Gao, Su

    2015-08-07

    To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. Indianapolis, Indiana. From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. Incident dementia and incident AD. After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.

  8. Statins for the primary prevention of cardiovascular disease

    Taylor, Fiona; Ward, Kirsten; Moore, Theresa HM; Burke, Margaret; Smith, George Davey; Casas, Juan P; Ebrahim, Shah

    2014-01-01

    Background Reducing high blood cholesterol, a risk factor for cardiovascular disease (CVD) events in people with and without a past history of coronary heart disease (CHD) is an important goal of pharmacotherapy. Statins are the first-choice agents. Previous reviews of the effects of statins have highlighted their benefits in people with coronary artery disease. The case for primary prevention, however, is less clear. Objectives To assess the effects, both harms and benefits, of statins in people with no history of CVD. Search methods To avoid duplication of effort, we checked reference lists of previous systematic reviews. We searched the Cochrane Central Register of Controlled Trials (Issue 1, 2007), MEDLINE (2001 to March 2007) and EMBASE (2003 to March 2007). There were no language restrictions. Selection criteria Randomised controlled trials of statins with minimum duration of one year and follow-up of six months, in adults with no restrictions on their total low density lipoprotein (LDL) or high density lipoprotein (HDL) cholesterol levels, and where 10% or less had a history of CVD, were included. Data collection and analysis Two authors independently selected studies for inclusion and extracted data. Outcomes included all cause mortality, fatal and non-fatal CHD, CVD and stroke events, combined endpoints (fatal and non-fatal CHD, CVD and stroke events), change in blood total cholesterol concentration, revascularisation, adverse events, quality of life and costs. Relative risk (RR) was calculated for dichotomous data, and for continuous data pooled weighted mean differences (with 95% confidence intervals) were calculated. Main results Fourteen randomised control trials (16 trial arms; 34,272 participants) were included. Eleven trials recruited patients with specific conditions (raised lipids, diabetes, hypertension, microalbuminuria). All-cause mortality was reduced by statins (RR 0.84, 95% CI 0.73 to 0.96) as was combined fatal and non-fatal CVD endpoints

  9. Statin adherence and the risk of Parkinson's disease: A population-based cohort study.

    Rozani, Violetta; Giladi, Nir; El-Ad, Baruch; Gurevich, Tanya; Tsamir, Judith; Hemo, Beatriz; Peretz, Chava

    2017-01-01

    While experimental data provided some compelling evidence on the benefits of statins on dopaminergic neurons, observational studies reported conflicting results regarding the potential of statins to effect the risk of Parkinson's disease (PD). To evaluate the association between changes in statin adherence over time and PD risk. A population-based cohort of new statin users (ages 40-79, years 1999-2012) was derived from a large Israeli healthcare services organization. Data included history of statin purchases and low density lipoprotein cholesterol (LDL-C) levels. Personal statin adherence was measured annually by the proportion of days covered (PDC). PD was detected employing a drug-tracer approach. Stratified (by sex, LDL-C levels at baseline and age) Cox proportional hazards models with time-dependent covariates were used to compute adjusted Hazard Ratio (HR) with 95%CI. The cohort included 232,877 individuals, 49.3% men. Mean age at first statin purchase was 56.5 (±9.8) years for men and 58.7 (±9.2) years for women. PDC distribution for the whole follow up period differed between men and women: medians 58.3% and 54.1% respectively. During a mean follow up of 7.6 (±3.4) years, 2,550 (1.1%) PD cases were identified. In a 1-year lagged analysis, we found no association between annual statin adherence and PD risk in all age-groups regardless of statin type and potency. Age-pooled HR (95%CI) for men and women with LDL-C levels at baseline ≤160mg/dL were: 0.99 (0.99-1.01), 1.01 (1.00-1.02); and for men and women with LDL-C >160mg/dL levels: 0.99 (0.98-1.01), 0.97 (0.98-1.01). Our findings suggest that statin adherence over time does not affect PD risk. Future studies should use large-scale cohorts and refining assessments of long-term profiles in statin adherence.

  10. 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).

    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.

  11. [Statin and risk of falls in the elderly: A sytematic review of the literature].

    Venegas Sanabria, Luis Carlos; Barbosa Balaquera, Stephany; Suarez Acosta, Ana María; García Peña, Ángel Alberto; Cano Gutiérrez, Carlos Alberto

    With the high incidence of cardiovascular events in the elderly population the effectiveness of statins in reducing mortality from coronary events has been demonstrated. However, there have been adverse effects, such as myalgia, myopathy, myonecrosis, not to mention the falls as a result of muscle damage with statin use. The purpose of this study is to conduct a systematic review to assess the literature on the association between statin use and the risk of falls. The databases that were included PUBMED AND SCOPUS, with articles published from January 2000 to May 2016. The MESH terms used for the search were "FALLS" AND "STATIN". Selected studies included cohort populations from the community (>50 years old), and analysed using the Scottish Intercollegiate (SIGN) methodology guidelines, as no randomised controlled study was found. In the study by Ham et al., statin use was shown to be a protective factor for presence of falls. In the second study by Scott et al., there was an increased risk of falls (P=.029) and an impairment in muscle strength and quality muscle (P=.033 and P=.046, respectively). In the third study Haerer et al., found an increased risk of falls (P=.63). The association between use of statins and risk of falls could not be determined with the available evidence, although an association with the involvement of some determinants of muscular function was found. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. The safety of statins in clinical practice.

    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.

  13. Statins and angiogenesis: Is it about connections?

    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.

  14. Statins and risk of breast cancer recurrence

    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

  15. Statin-Associated Autoimmune Myopathy: A Systematic Review of 100 Cases.

    Nazir, Salik; Lohani, Saroj; Tachamo, Niranjan; Poudel, Dilliram; Donato, Anthony

    2017-04-01

    Statins are a group of drugs that reduce the levels of triglycerides and cholesterol in blood by inhibiting HMG-CoA reductase, an enzyme involved in rate limiting step in cholesterol synthesis. About 2-20% patients on statins develop toxic myopathies, which usually resolve on discontinuation of statin. More recently, an immune-mediated necrotizing myopathy has been found to be associated with statin use which in most cases requires treatment with immunosuppressants. To perform a systematic review on published case reports and case series of statin-associated autoimmune myopathy. A comprehensive search of PUBMED, EMBASE, Cochrane library and ClinicalTrials.gov databases was performed for relevant articles from inception until March 19, 2016 to identify cases of statin-associated necrotizing myopathy and characterize their symptoms, evaluation and response to treatment. A total of 16 articles describing 100 patients with statin-associated autoimmune myopathy were identified. The mean age of presentation was 64.72 years, and 54.44% were males. The main presenting clinical feature was proximal muscle weakness, which was symmetric in 83.33% of patients. The mean creatine kinase (CK) was 6853 IU/l. Anti-HMG-CoA reductase antibody was positive in all cases tested (n = 57/57, 100%). In patients with no anti-HMG-CoA antibody results, diagnosis was established by findings of necrotizing myopathy on biopsy. Among the 83 cases where muscle biopsy information was available, 81.48% had necrosis, while 18.51% had combination of necrosis and inflammation. Most (83.82%) patients received two or more immunosuppressants to induce remission. Ninety-one percent had resolution of symptoms after treatment. Statin-associated necrotizing myopathy is a symmetric proximal muscle weakness associated with extreme elevations of CK. It is common in males and can occur after months of statin use. It is associated with necrosis on muscle biopsy and the presence of anti-HMG-CoA reductase antibodies

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

    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

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

    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

  18. NEW POSSIBILITIES OF STATIN THERAPY IN ARTERIAL HYPERTENSION

    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

  19. Statin use and survival following glioblastoma multiforme

    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....

  20. Statin use and risk of endometrial cancer

    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...

  1. Statins: antimicrobial resistance breakers or makers?

    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

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

    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

  3. Persistent lipid abnormalities in statin-treated patients with diabetes mellitus in Europe and Canada: results of the Dyslipidaemia International Study

    Leiter, L. A.; Lundman, P.; da Silva, P. M.; Drexel, H.; Jünger, C.; Gitt, A. K.; Absenger, Guun; Albrich, Ernst; Allinger, Berndt; Allinger, Stephan; Anacher, Gerald; Angermayr, Gertraud; Angermeier, Hermann; Anzengruber, Aneas; Archimanitis, Gabriele; Arnsteiner, Patricia; Auberger, Wolfgang; Azhary, Mawaheb; Barfuss, Michael; Bauer, Christian; Bauer, Birgit Elisabeth; Beclin, Thomas; Binder, Thomas; Binder, Gabriele; Böhler, Dietmar; Brändle, Johann; Breslmair, Jörg; Brettlecker, Marlis; Bürger, Michael; Calvi, Inge; Dorfinger, Werner; Doringer-Schnepf, Elisabeth; Eer, Anton; Eckmayr, Christine; Eder, Franz; Egermann, Margit; Erath, Michael; Etzinger, Michael; Etzinger, Claudia; Fiedler, Lothar; Filip, Wolfgang; Filip, Michaela; Föchterle, Johann; Fodor, Anita; Frieden, Thomas; Gareiss, Mertens; Gföllner, Peter; Ghamarian, Thomas; Goritschan, Michael; Haar, Klaus; Habeler, Gerhard; Hadjiivanov, Valery; Haiböck, Christian; Hammer, Regina; Hartmann, Siegfried; Haschkovitz, Herbert; Hauer, Walter; Hauer, Josef; Haunschmidt, Christian; Heimayr, Christine; Hengl, Wolfgang; Hengl, Gunter; Hermann, Rudolf; Herrmann, Rainer; Hillebrand, Roswitha; Hintersteininger, Otto; Hirsch, Michael; Hitzinger, Martin; Hochegger, Tanja; Hockl, Wolfgang; Hoi, Michael; Hörmann, Jan; Hudler, Brigitte; Imb, Gerhard; Joichl, Anea; Jungbauer, Karl; Kapl, Gerlinde; Kerschbaum, Margit; Kienesberger, Franz; Killinger, Gerhard; Kitzler, Gerhard; Klein, Franz; Kleinbichler, Dietmar; Kohr, Anton; Kopetzky, Michael; Korthals, Christian; Kortschak, Werner; Koschutnik, Martin; Kraus, Werner A.; Kurzemann, Susanne; Lavicka, Claus; Lehner, Guido; Lenz, Jürgen; Lepuschütz, Sabine; Lichtenwallner, Michael; Lober, Reinhard; Loidl, Christine; Lopatka, Eduard; Ludwig, Rudolf; Maca, Thomas; Mair, Anneliese; Mandak, Michael; Margreiter, Maria; Margreiter, Anea; Markovics, Michael; Matejicek, Frieich; Mohilla, Maximillian; Moll, Christian; Mörz, Beate; Mörz, Reinhard; Nagl, Heinz; Neumayr, Günther; Oberroitmair, Helmut; Oberzinner, Michael; Pallamar, Walter; Pangratz, Sibylle; Parandian, Laurenz; Paulus, Alexana; Pfaffenwimmer, Christoph; Plaichinger, Peter; Pokorn, Thomas; Polanec, Helmuth; Pöll-Weiss, Barbara; Pralea, Doralina; Puttinger, Johann; Quinton, Thomas; Ranegger, Matthias; Rass, Sepp; Rauch, Heribert; Riehs, Manfred; Robetin, Erich; Rohringer, Jörg; Rupprechter, Josef; Sadjed, Eduard; Schimbach, Johann Alois; Schmid, Jutta; Schneiderbauer, Rotraud; Schopper, Wolfgang; Schulze-Bauer, Alfred; Schuster, Gottfried; Schwarz, Johann; Schwarz, Maria; Schweighofer, Christoph; Schwelle, Franz; Simma, Hanspeter; Sock, Renate; Sock, Reinhard; Sprenger, Fritz; Stiglmayr, Thomas; Stocker, Ilse; Stütz, Pia; Tama, Mustafa; Teleky, Ursula; Tschauko, Werner; Veits, Martin; Vikydal, Gerhard; Vlaschitz, Karl; Wais, Elisabeth; Wais, Adam; Wegmann, Robert; Wehle, Franz; Weindl, Manfred; Weinhandl, Manuela; Wendt, Ursula; Wendt, Klaus; Werner-Tutschku, Volker; Werner-Tutschku, Christine; Wilscher, Josef; Wind, Norbert; Winter, Aneas; Wolfschütz, Gerald; Wolfsgruber, Markus; Wolfsgruber, Brigitte; Wurm, Renate; Ziebart-Schroth, Arno; Zimmermann, Maximillian; Zinnagl, Aneas; Zirm, Anea; Zirm Canada, Bernhard; Bokenfohr, Grace Mary; Liu, Edmond K. H.; Melling, Gordon W.; Papp, Edward William; Sachdeva, Ashok K.; Snyman, Ernst Retief; Varma, Sonya; Ward, Richard A.; Tiong Wong, Anew Pak; Basson, Paul J.; Brodie, Brian D.; Chahal, Sukhjiwan Jeevyn; Chan, William Y.; Chow, John C.; Cormack, Maura; Eddy, Donald H. J.; Ezekiel, Daniel; Farquhar, Anew; Gu, Shian; Hii, Ting H.; Ho-Asjoe, Marianne P. K.; Hosie, Anew; Jaffer, Shahin; Jakubowski, Anew T.; Karim, Mandy; Kiai, Cristina; Kooy, Jacobus; Lytle, Craig R.; Mcleod, Kevin Lain; Morgan, David C.; Myckatyn, Michael M.; Ng, John P. Y.; Schriemer, Ronnald; Schumacher, Gerhard; Grey Stopforth, James; Hoo Tsui, Winston Wai; Wilson, Robin T.; Wong, Danny; Wong, Wilfred T.; Yeung, Margaret M. W.; Cram, David Harvey; Kumari Dissanayake, Dilani Tamara; Gerber, Johan Daniel W.; Haligowski, David; Hrabarchuk, Blair; Kroczak, Tadeusz J.; Lipson, Alan H.; Mahay, Raj K.; Wessels Mare, Abraham Carel; Mohamdee, Feisal John; Olynyk, Frederick Theodore; Pieterse, Wickus; Ramgoolam, Rajenanath; Rothova, Anna; Saunders, Kevin Kenneth; Szajkowski, Stanley; van Gend, Richard F.; van Rensburg, Nicolaas Marthinus Jansen; Anand, Sanjiv; Baer, Carolyn E. H.; Basque, Eric J. Y.; Benaya, Sebastian; Bessoudo, Ricardo; Bhalla, Jaswinder; Chettiar, Nataraj V.; Craig, Brian N.; Desrosiers, France; Ranjani Imbulgoda, Manel; Morgan, Gareth M.; Nowak, Zbigniew J.; Scott, Daniel G.; Searles, Gregory R.; Slorach, J. Ninian; Stevenson, Robert N.; Browne, Noel John; Bruff, Karl Joseph; Collingwood, John Maurice; Collins, Wayne; Over, Aidan; Gabriel, Anthony M.; Govender, Moonsamy; Hart, David G.; Hatcher, Lydia B.; Janes, John; Kielty, John F.; Krisdaphongs, Michoke; Lush, Richard Boyd; Moulton, William Bertram; Riche, Cyril R.; Rideout, Gary M.; Roberts, Bernard C.; Walsh, Paul E.; Wight, Harold G.; Woodland, K. Heather; Woodland, Robert C.; Atkinson, Bradley Charles; Chow, Carlyle S. H. A.; Collins, James A.; Graham, Robert D.; Hosein, Jalal; Machel, Teresa M.; Mahaney, Gordon Ralston; Mclean, James Robert Bruce; Murray, Michael R.; Myatt, Gregory Alexander; Ozere, Christopher P.; Saha, Amal Krishna; Sanders, David Herbert; Seaman, Donald Maxwell; Seaman, James Gordon; Swinamer, Deanna; Voon Yee, Kenny Yew; Ali, Mohamed Mustapha; Bankay, Clarence D. C.; Beduhn, Eitel Erich Reinhold; Callaghan, Denis J.; Chan, Yun Kai; Chaudhri, Arif R.; Chen, Richard Y. Y.; Conway, James Robin; Cunningham, William L.; Cusimano, Steven Lawrence; Souza, Eleanor De; de Souza, Selwyn X.; Deyoung, John Paul; Epstein, Ralph; Faiers, Alan Arthur; Figurado, Victor John; Forbes, F. Basil Trayer; Gabor, Zsuzsanna; Gallardo, Rodolfo Canonizado; Gaur, Shiva K.; George, Elizabeth; Hartford, Brian J.; Shiu-Chung Ho, Michael; Ho, Chung; Ismail, Shiraz H.; Bhushan Kalra, Bharat; Koprowicz, Kinga; Kumar, Naresh; Lam, Clement; Lau, Ming-Jarm; Law, Hugo Kwok Cheung; Fung, Max Leung Sui; Liutkus, Joanne Frances; Lotfallah, Talaat K.; Luton, Robert G.; Meneses, Gloria S.; Miller, Mark Lee; Nagji, Noorbegum; Ng, Ken H. M.; Ng Thow Hing, Roland E.; Pandey, Amritanshu Shekhar; Petrov, Ivan; Rosenthall, Wendy; Rudner, Howard; Russell, Alan Douglas; Sanchez, Zenia A.; Shaban, Joseph A.; Shariff, Shiraz B. K.; Shih, Chung Ming; Sinclair, Duncan W.; Spink, Donald Richard; Tung, Tommy Hak Tsun; Vizel, Saul; Yanover, David Frederick; Zavodni, Louis S.; Cusack, Paul; Dewar, Charles M.; Hooley, Peter; Kassner, Rachel Anne; Mackinnon, Randy James; Molyneaux, Harold W.; Shetty, Karunakara Naduhithlu; Barrière, Ginette; Berjat, Maria B.; Bernucci, Bruno; Bérubé, Claude; Boueau, Ghyslain; Chehayeb, Raja; Ciricillo, Domenico; Constance, Christian M.; Côté, Gilles; Desroches, Jacques; Gagnon, Robert; Gaueau, Gilles; Godbout, Jean Louis; Harvey, Pierre; Hassan, Youssef; Hoang, Ngoc Vinh; Houde, Danielle; Lalonde, Alain-Paul; Lavoie, Régis; Leclair, Normand; Meagher, Luc; Ouimet, Alain; Plourde, Simon; Rioux, Denis W.; Roberge, Claude; Roy, Bruno; Sasseville, Richard; Serfaty, Samuel; Theriault, Lyne; Timothée, Jean R.; Tjia, Sabine; Tremblay, Bruno; Turcotte, Jean; Bose, Sabyasachi; Aletta Bouwer, Hester; Chernesky, Patricia A.; Johnson, Mervin Louis; Kemp, David R.; Lai, Raymond Pong-Che; Lee, Frank R.; Lipsett, William G. C.; Lombard, Schalk J.; Majid, Falah S.; Malan, Johannes J.; Maree, Narinda; Nayar, Arun; Nel, Mandi; Oduntan, Oluwole O.; Rajakumar, Alphonsus R. J.; Baraka Ramadan, Fauzi; Shamsuzzaman, Mohammed; Vermeulen, Abraham P. M.; Fred, C.; Anthonsen, Birgitte; Ardest, Steen Pennerup; Arnold-Larsen, Susanne Kajsa; Axelsen, Allan; Barfoed, Klaus; Birkler, Niels Erik; Blokkebak, Jens; Boserup, Jørgen; Kettrup Brassøe, Jens Ole; Chovanec, Martin; Lykke Christensen, Bendt; Christensen, Micael; Skjøth Christensen, Randi; Eidner, Per Olav; Eisbo, Jørn; Elsvor, Jan; Engmann, Ida Veng-Christensen; Eriksen, Rene Milling; Frederiksen, Thorkil; Frølund, Hanne Charlotte; Garne, Susanne; Giørtz, Agnete; Gregersen, Bettina; Halkier, Merete Lundbye; Hansen, Jens Georg; Harder, Jan; Jørgen, Hans; Henriksen, O.; Kirkeby Hoffmann, Michael; Holk, Erik; Hollensen, Jan; Jacobsen, Rune; Jakobsen, Lotte; Jensen, Christian; Jensen, Morten; Jensen, Vibeke; Jepsen, Peter; Johannsen, Jens Arne; Verner Johansen, Lars; Johansen, Ole Steen; Juul, Kristian; Jørgensen, Arvid Frank; Jørgensen, Peter; Jørgensen, Ulrik Miilmann; Kensmark, Lars; Kjellerup, Carsten; Kjaer, Ejner; Kjaersgaard, Morten; Klubien, Peter; Kolby, Peter; Korsgaard Thomsen, Kristian; Krebs, Peter; Kristiansen, Tom; Lyng, Flemming; Madsen, Natalia V.; Meyer-Christensen, Jesper; Mogensen, Ole; Mortensen, Finn; Nielsen, Lotta Marie; Nielsen, Per Schiwe; Nielsen, Søren Kjærem; Ommen, Henrik; Juhl Otte, Jens; Østergaard Paridon, Volle; Parm, Michael; Peampour, Kian; Petersen, Kirsten; Pilgaard, Peder Jensen; Poulsen, Svend Erik; Preisler, Thomas; Hast Prins, Søren Ulrik; Randløv, Annette; Rasmussen, Birgit Reindahl; Elmegaard Rasmussen, Peter; Rasmussen, Regnar; Roed, Søren Flemming; Sander, Kirsten Foltmar; Schmidt, Ejnar Ørum; Jørgen Schultz, Paul; Smidemann, Margit; Solgaard, Jørgen; Stripp, Tommy; Søderlund, Michael Rene M.; Søgaard, Henning; Søndergaard, Dorte E.; Sørensen, Birgitte H.; Sørensen, Gerhard Seth; Thøgersen, Niels; Toftdahl, Hans; Uggerhøj, Hanne; Uhrenholt, Bjarne; Veronika Ullisch, Eva; Valentiner-Branth, Christian; Vinberg, Jørgen; Vinter, Svend Aage; Vittrup, Preben; Winther-Pedersen, Niels; Wøldike, Anne Grete; Zederkof, Jørgen M.; Thue Østergaard, Merete; Abiven, Patrick; Abraham, Dominique; de Beaumais, Philippe Adam; Ado, Jean Pierre; Affres, Helene; Agache, Regis; Airault Leman, Anne Marie; Moussarih, Abdallah Al; Albaric, Christian; Allaouchiche, Thierry; Allignol, Christian; Ammor, Mohammed; Ammoun Bourdelas, Corinne; Amsallem, Luc; Anquez, Denis; Antonini, Jean Michel; Assuied, Virginia; Attia, Gerard; Audebert, Olivier; Audibert, Henri; Ayach, Claude; Bagdadlian, Serge; Bagni, Marina; Baillet, Jean; Ballivian Cardozo, Fernando; Baranes, Robert; Barbier, Patricia; Barousse, Francoise; Bas, Sylvie; Battaglia, Jean Marc; Baudonnat, Bruno; Bauple, Jean Louis; Domengetroy, Frederic Baylac; Beard, Thierry; Beaumier, Eric; Beaumont, Jean Francois; Baylac Domengetroy, Frederic; Beck, Christian; Behar, Michel; Behr, Bernard; Benady, Richard; Benghanem, Mohamed Mounir; Benichou, Herve; Bensoussan, Jean Marc; Bensussan, Pierre; Bercegeay, Pascal; Berneau, Jean Baptiste; Bertolotti, Alexane; Bertrand, Sylviane; Besson, Alain; Bezanson, Christophe; Bezier, Christophe; Bezzina, Remy; Bichon, Herve; Bickar, Pierre; Billot, Pierre; Billot Belmere, Marie Claude; Bisson, Francois; Blanc, Dominique; Bloch, Jean Luc; Bloch, Bernard; Blondin, Hyacinthe; Blot, Jacques; Bloud, Raymond; Blouin, Pascal; Boesch, Christophe; Boiteux, Jean Luc; Bonnafous, Pierre; Bonneau, Yanick; Bonnefoy, Laurent; Borg, Bernard; Borys, Jean Michel; Brunehaut Petaut, Myriam; Boschmans, Sabine; Said, Rami Bou; Bouallouche, Abderrahmane; Bouchet, Jacques; Bouchlaghem, Khaled; Boulen, Yvon; Bouline, Benoit; Bounekhla, Mohamed Salah; Bouquin, Vincent; Bourgeois, Marie Brigitte; Bourgois, Didier; Brandily, Christian; Brandt, Pierre; Branquart, Frederic; Breilh, Patrick; Brilleman, Fabrice; Brisson, Thierry; Brocard, Francis; Bruel, Pierre; Brun, Jean Pierre; Buisson, Jean Gabriel; Buisson Virmoux, Isabelle; Bur, Christian; Cabal Malville, Elodie; Cabantous, Serge; Cabrol, Pierre; Cagnoli Gromovoi, Sylviane; Caillaux, Bruno Xavier; Caillot, Didier; Canchon Ottaviani, Isabelle; Canu, Philippe; Caramella, Alexana; Caramella, Alexane; Cardaillac, Christian; Carrivale, Alain; Cartal, Jean Pierre; Cassany, Bernard; Cauon, Bernard; Causeret, Jean Marie; Caye, Philippe; Cayet, Jean Paul; Cazor, Gilles; Cesarini, Joel; Chakra, Georges; Chambeau, Bernadette; Chambon, Valerie; Chanas, Jack; Chapuzot, Patrick; Charon, Ane; Charpin, Eric; Charton, Frederic; Cheikel, Jean; Chemin, Philippe; Chennouf, Kamel; Chequel, Henri; Chevrier, Denis; Ciroux, Patrick; Cissou, Yves; Claeys, Jean Luc; Clariond, Yves; Classen, Olivier; Cloerec, Ane; Clouet, Sophie; Cloup Lefeuvre, Anne Marie; Cochet, Chantal; Cocuau, Didier; Cohen, Henri; Cohen Presberg, Pascale Cohen; Colin, Stephane; Colin, Remy; Colucci, Robert; Come, Philippe; Condouret, Pierre; Conturie, Agnes; Corbin, Ane; Corticelli, Paola; Coste, Daniel; Cotrel, Olivier; Coueau, Sylvie; Coulon, Paul; Courdy, Christian; Courtin, Marc; Courtot, Pierre; Coutrey, Laurent; Couval, Rene; Cravello, Patrick; Cressey, Olivier; Cuisinier, Yves; Cunin, Bernard; Cunnington, Bernard; Cusseau, Herve; Cuvelier, Christian; Arailh, Bruno D.; Dabboura, Adib; Dages, Laurence; Dahmani, Noureddine; Dandignac, Jean Christophe; Daney, Dominique; Dannel, Bernard; Darbois, Dominique; Dareths, Philippe; Daubin, Daniel; David, Jean Claude; de Foiard, Patrick; de Mallmann Guyot, Veronique De; de Wit, Marie Astrid; Debast, Francoise; Deboute, Eric; Debuc, Jean Pierre; Dechoux, Edouard; Decloux, Olivier; Decruyenaere, Yannick; Dejans, Jacques Maurice; Delarue, Michel; Delattre, Xavier; Delmaire, Patrick; Denis, Lucien; Deschamps Ben Ayed, Myriam; Devins, Pascal; Dezou, Sylvie; Dieuzaide, Pierre; Dirheimer, Bertrand; Dominguez, Paul; Donadille, Florence; Dondain, Benoit; Doridan, Pierre; Ouhet, Pascal; Dubois, Arnaud; Dubois, Ane; Ducharme, Pascal; Duchez, Paul; Dulard, Catherine; Dumoulin, Marc; Duprey, Georges; Durand, Jacques; Mohamed, Ibrahim; Chehab, El; Emery, Bernard; Emmanuel, Georges; Ashari, Ghazaleh Esna; Evrard, Eric; Fargeot Lamy, Aleth; Farges, Jean Louis; Faucher, Patrick; Faucie, Alain; Faure, Yves; Favre, Jean Jacques; Felipe, Jean Louis; Feret, Daniel; Ferragu, Alain; Ferrandin, Gerard; Ferriot, Francois; Finelle, Laurent; Flond, Jacques; Foieri, Jean; Fol, Stephane; Fontaine, Brigitte; Forichon, Dominique; Foucry, Michel; Fournier, Jean Francois; Fregeac, Bernard; Fuchs, Martin; Gabriel, Franck; Gaimard, Didier; Gallois, Stephane; Garapon, Georges; Garas, Mamdouh; Garcia, Pierre; Garcia, Jean Michel; Garcia, Marie Pierre; Garman, Waddah; Garzuel, Dominique; Gaspard, Jean Marc; Gauci, Laurent; Gautheron, Patrick; Gauthier, Jacques; Gauthier Lafaye, Pierre Yves; Gay, Michel Charles; Gay Duc, Bernadette; Gayout, Olivier; Gegu, Yann; Gentile, Francois; Germain, Emmanuel; Gharbi, Gerard; Gigandet Tamarelle, Catherine; Gilardie, Alain; Gilles Verliat, Martine; Gillet, Thierry; Gnana, Philippe; Goguey, Alain; Gombert, Alain; Gonin, Bernard; Gonzales, Philippe; Goulesque, Xavier; Graba, Jean Marc; Granier, Alain; Greiner, Olivier; Groboz, Martial; Gromoff, Serge; Grossemy, Xavier; Grossi, Christian; Guenin, Frederic; Gueranger, Pierre; Guerin, Patrick; Guerineau, Jean Pierre; Guessous Zghal, Fathia; Guicheux, Dominique; Guillere, Jacqueline; Guyonnet, Gilles; Haddad, Samir; Hadj, Nordine; Hamani, Djamel; Hamm, Jacky; Hammoudi, Djamal; Harle, Xavier; Harnie Coussau, Pierre; Hazen, Richard; Hembert, Francois; Hemon, Pierre; Hergue, Michel; Hestin, Christian; Heyraud, Luc; Hindennach, Dieter; Hirot, Etienne; Ho Wang Yin, Chan Shing; Hocquelet Denis, Catherine; Hoppe, Patrice; Horovitz, Daniel; Hours, Jean Michel; Houta, Benjamin; Hua, Gerard; Hui Bon Hoa, Nicole; Humez, Philippe; Hurier, Michel; Husson, Gerald; Hyvernat, Guy; Ichard, Jean Francois; Impens, Claude; Iovescu, Decebal; Jacob, Philippe; Jacob, Gildas; Jacquemart, Jean Pierre; Jacquier, Philippe; Jahanshahi Honorat, Shideh; Jalladeau, Jean Francois; Jan, Luc; Jannel, Yves; Jarrige, Vincent; Jeremiasz, Richard; Annick Jestin Depond, Marie; Joseph, Michel; Joseph Henri Fargue, Helene; Joubrel, Alain; Jouet, Alain; Julien, Bruno; Jullien, Francois; Jullien, Jean Louis; Kadoche, David; Kahl, Etienne; Kanawati, Aiman; Khalife, Sami; Khettou, Christophe; Kiers, Jean Paul; Kissel, Christian; Klein, Jean Claude; Klopfenstein, Samuel; Koch, Alexis; Koenig, Georges; Kohler, Philippe; Koriche, Abdelmalek; Labernardiere, Nicole; Labet, Philippe; Lablanche, Fabien; Laborde Laulhe, Vincent; Lagorce, Xavier; Laine, Eric; Lalague, Pascal; Laleu, Jean Noel; Lambert, Michel; Lambert Ledain, Mireille Lambert; Lambertyn, Xavier; Lame, Jean Francois; Langlois, Frederic; Lanoix, Eric; Laprade, Michel; Lasseri, Charaf; Laterrade, Bernard; Laurent, Jean Claude; Laurier, Bernard; Laval, Laurent; Le Borgne, Patrick; Le Franc, Pierre; Le Henaff, Patrick; Le Noir de Carlan, Herve; Le Roy, Jean Pierre; Le Roy Hennion, Florence; Lebon, Louis; Lecler, Olivier; Leclerc, Philippe; Ledieu, Christian; Lefebvre, Bernard; Lefevre, Philippe; Lehujeur, Catherine; Leiber, Christian; Leick, Gerard; Lemberthe, Thierry; Lenevez, Norbert; Lenoble, Patrick; Leriche, Philippe; Leroux, Eric; Leroy, Jean Michel; Leroy, Christian; Lescaillez, Dominique; Leurele, Christian; Lhermann, Sophie; Libermann, Pierre; Licari, Gilbert; Lo Re, Antoine; Long, Philippe; Long, Jean Louis; Lormeau, Boris; Louchart, Jean Christophe; Lucas, Jean Pierre; Luquet, Thierry; Lussato, Philippe; Maarouf, Moustapha; Mabilais, Francois; Magnier Sinclair, Christine; Mahot Moreau, Pascale; Malafosse, Denis; Mandirac, Jean Paul; Manolis, Jerome; Mante, Jean Pierre; Maquaire, Claude; Marchal, Thierry; Marchand, Guillaume; Marillesse, Olivier; Marmier, Gabriel; Herve Maron, Yves; Marrachelli, Nadine; Marsaux, Michel; Martin, Bruno; Martin, Michel; Deiss, Pascale Martin; Masson, Arnaud; Mativa, Bruno; Matton, Jean Francois; Mauffrey, Jean; Mauriere, Serge; Maurois, Georges; Maury, Joceline; Mayer, Frederic; Menu, Pierre; Mercier, Bernard; Messmer, Daniel; Mestiri, Sami; Meyer, Gilles; Michaelides, Michael; Michaud, Gilles; Michenaud, Bernard; Mielot, Stephane; Millory Marco, Jerry Anne; Mingam, Stephane; Mira, Reginald; Mius, Stephane; Monnier Meteau, Marie Paule; Mora, Francis; Morbois Trabut, Louise; Morosi, Laurent; Mougeolle, Jean Luc; Mouget, Jean Louis; Mouroux, Daniel; Mouthon, Jean Marie; Muller, Jacques; Nakache, Ane; Narbonne, Herve; Navarranne Roumec, Anne; Navarro, Pierre; Neubrand, Jean Yves; Nguyen, Quang Thieu; Nguyen Quang, Guy; Nguyen Xuan, Thong; Niot, Patrice; Oudart, Jean Maurice; Outteryck, Alain; Pages, Jean Marie; Paillet, Charles; Pain, Jean Marie; Pangaud de Gouville, Patricia; Paquin, Olivier; Parent, Vincent; Parer Richard, Claire; Parrot, Francine; Parthenay, Pascal; Pascariello, Jean Claude; Passebon, Jean Claude; Pere, Alain; Perelstein, Laurent; Perot, Michel; Petit, Richard; Petit, Philippe; Petit, Francois; Petruzzi, Philippe; Phelipeau, Denis; Philippon, Jean Claude; Philippon, Gilles; Picard, Bruno; Picard, Jean Claude; Picot, Bernard; Piera, Jean Francois; Pieri, Alain; Piffoux, Eric; Pilard, Patrick; Pillet, Alain; Pinot, Philippe; Pinzani, Alain; Pleskof, Alain; Plessier, Jean Claude; Plisson, Alain; Pochon, Claude; Poggi, Valerie; Poirat, Alain; Poiree, Maurice; Polleux, Janick; Noel Pontecaille, Jean; Posocco, Regis; Pospiech, Jean Claude; Pradies, Felix; Prevot, Remi; Pueyo, Jean Bernard; Quaelli, Jacques; Rabbia, Michel; Rabemananjara, Aimery; Rami, Saad; Rapin, Jean Jacques; Rasquin, Corinne; Ratinaud, Didier; Reboud, Bruno; Reboul, Philippe; Reichman, Jean Jacques; Reinhardt, Patrick; Renard Houta, Catherine Renard; Reverdy, Olivier; Revol, Michel; Rey, Pierre Alain; Richardeau, Yves; Rives, Bernard; Robida, Christine; Rochez Fraiberg, Muriel; Rodet, Jean Pierre; Rolland, Jean Francois; Romand, Bruno; Romano, Jean Paul; Rosati Gretere, Chantal; Rosey, Alain; Rosset, Martial; Rossi, Jean Pierre; Rouquette, Georges; Rousseau, Michel; Rousselon, Xavier; Roy, Christophe; Royer, Denis; Ruetsch, Marcel; Saade, Maurice; Saby Kuchler, Nicolas; Samar, Guy; Sanchez, Pierre Yves; Sane, Alain; Sanz, Jean Paul; Sardon, Michel; Sarrazin, Marc Eric; Sasportes, Gilbert; Saudou, Francis; Sauze, Elisabeth; Savary, Pascal; Schenowitz, Alain; Schmartz, Pierre; Schoepfer, Marc Olivier; Seewagen, Jacques; Serramoune, Denis; Serre, Christian; Sicard Guroo, Helene; Sichãc, Jean Philippe; Sifaoui, Sylvain; Simoncello, Marc; Simonin, Marie Jeanne; Simonnet, Jean Francois; Spindler, Didier; Steier, Alain; Sultan, Charles Raphael; Taghipour, Kouroch; Talayrach, Bruno; Talbot, Francois; Talhouarn, Vanessa; Tallec, Yves; Tarasco Schenrey, Elisabeth; Tarrene, Michel; Tater, Dominique; Tessier, Bernard; Teste, Marie; Thierry, Dominique; Thiollier, Patrice; Thoreau, Frederic; Thual, Jean; Traen, Vincent; Trigano, Jacques Alexane; Troussier, Jean Bernard; Truong Ky Minh, Bernard; van Melckebeke, Gerard; Vaque, Philippe; Vaucelle, Celine; Vedel, Eric; Venu, Didier; Verdavoine, Patrick; Vergeron, Jean; Viallon, Philippe; Viault, Dominique; Vieules, Jean Max; Vigier, Jean Paul; Vilain, Jean Marie; Villard, Bruno; Vitoux, Jean Francois; Viviand, Paul; Vivien, Olivier; Walter, Patrice; Waquier, Patrick; Waszkiewicz, Jean Marc; Weidich, Stephane; Westerfeld, Raymond; Weynachter, Gerald; Wilhelm, Pierre; Wolff, Claude; Wursthorn, Marc; Zammattio, Didier; Zylinski, Bernard; Lauer, Peter; Kühn, Uwe; Weltzel, Wolfgang; Mohr, Hella; Weyland, Klaus; Spittel, Bärbel; Böhm, Günter; Ferdowsy, Said; Hanusch, Peter; Spiekermann, Josef; Albert, Edwin; Stuff, Karl; Jungmair, Wolfgang; Koller, Sabine; Schubert, Wilhelm; Schlehahn, Fred; Bormann, Gundula; Graf, Kristof; Stiehler, Gisela; Bock, Manfred; Müller, Angelika; Haufe, Michael; Nielsen, Lorenz; Raum, Doris; Rogler, Karin; Bürstner, Joachim; Völk, Hans-Jörg; Sachse, Michael; Escher, Torsten; Doumit, Adel; O'dey, Hildegard; Holzmann, Ulrike; Sauer, Hermann; Schellenberg, Gottfried; Carius, Jürgen; Dänschel, Wilfried; Kopf, Aneas; Zerr, Elena; Tatalovic, Ratko; Rupp, Heiun; Anders, Elfriede; Mende, Marion; Volk, Ulrich; Hagenow, Aneas; Lang, Thomas; Schmitz, Karl-Heinz; Gössling, Jan-Henik; Mutsch, Günther; Steidel, Joachim; Osten, Klaus; Giokoglu, Kiriakos; Bellisch, Sabine; Füll, Katja; Walther, Wolfgang; Flick, Sabine; Dünnebier, Rosemarie; Dharmawan, Ichsan; Schönmehl, Wolfgang; Hoss, Valentin; Kipping, Stephan; Wolf, Hans-Joachim; Wolf, Hans-Frieich; Willmann, Volker; Bugarski, Bruno; Hoffschröer, Josef; Von Wallfeld, Siegrun; Ruhland, Guun; Bulling, Daniel; Häusler, Maren; Haustein, Gabriele; Kallenbach, Cornelia; Schwemmler, Claudia; Frank, Antje; Lodder-Bender, Ulrike; Rawe, Klaus; Reinert, Hans-Ferdinand; Schönhof, Petra; Fahrenschon, Klaus; Schorcht, Elisabeth; Etzold, Erika; Brehm, Michael; Paust, Wolf-Dieter; Schulte-Kemna, Achim; Pötter, Klaus-Werner; Ott-Voigtländer, Ulrike; Schwenke, Reto; Thinesse-Mallwitz, Manuela; Siml, Steffi; Stern, Hirene; Roelen, Harald; Scherhag, Klaus-Peter; Matulla, Petra; Herrmann, Hans Joachim; Neumann, Gerhard; Barbuia, Marius; Vormann, Reinhold; Hitzler, Karl; Linum, Aneas; Hanke, Klaus; Hohberg, Hans-Joachim; Klingel, Roger; Hohnstädter, Rainer; Klasen, Hartmut; Aschermann, Peter; Grau, Wilfried; Killinger, Paul; Gross, Kathrin; Naus, Rainer; Todoroff, Karin; Zühlke, Wolfgang; Kellner, Hanns-Ulrich; Hager, Eva; Thieme, Jochen; Kornitzky, Michael; Rösch, Volker; Heinze, Elke; Hiederer, Wolfgang; Konz, Karl-Heinz; Köhler, Michael; Diekmann, Martin; Junghans, Edith; Dietermann, Friedgard; Kerp, Ekkehard; Schäfer-Lehnhausen, Silvia; Kruck, Irmtraut; Ettelt, Rolf; Hölscher, Aneas; Kittler, Sybil; Jung, Heiun; Mailänder, Albert; Nowara, Peter; Ritschl, Harald; Mödl, Bernhard; Gallwitz, Torsten; Meyer, Stephan; Peter, Anton; Peters, Otto; Pflaum, Petra; Fröhlich, Karl-Heinz; Mertens, Hans-Jürgen; Merlin-Sprünken, Verena; Erpenbach, Klaus; Fervers, Frank; Kuhl, Ulrike; Halsig, Friedemann; Rein, Wilfried; Hauser, Ernst-Richard; Laubenthal, Florin; Richard, Frank; Langer, Claus; Lange, Rainer; Eska, Jan; Mohanty, George; Lange, Isengard; Eltges, Nicole; Kuntz, Christoph; Mechery, Thomas; Vöckl, Josef; Viergutz, Christoph; Stähle-Klose, Claudia; Sohr, Katja; Böhler, Steffen; Brecke, Georg; Burls, Malcolm; Werner, Karl-Michael; Vorpahl, Ralf; Stahl-Weigert, Beate; Bunge, Gerd; Thomsen, Jutta; Blessing, Erwin; Bengel, Bengel; Buhlmann, Ulla; Tröger, Tröger; Sippel, Sippel; Vossschulte, Vossschulte; Wilms, Wilms; Appelt, Appelt; Dauterstedt, Dauterstedt; Witte, Witte; Böttger, Uta; Wyborski, Waltraud; Strache, Sabine; Böttger, Werner; Zeiner, Luise; Wuttke, Wanda; Stoidner- Amann, Annette; Stoermer, Brigitte; Bock, Stephan; Groos-März, Cornelia; Thamm, Maria-Elisabeth; Meier, Josef; Schneider, Martin; Niessen, Ulrich; Storm, Gernot-Rainer; Streitbürger, Elmar; Münkel, Thomas; Palfi, Mihai; Naumann, Ulrich; Tannhof, Gabriele; Streibhardt, Frank; Gebhardt, Wolfgang; Nieswandt, Gerhard; Gerke, Ulrich; Nöhring, Axel; Bott, Jochen; Goertz, Jutta; Winkler, Dietmar; Lotter, Edith; Kraaz, Katja; Bärwinkel, Petra; Hildebrandt, Diana; Weyers, Georg; Kubin-Siring, Birgit; Baier, Eduard; Weber, Thomas; Holz, Dirk-Egbert; Wolfers, Johannes; Kihm, Wolfgang; Kamali-Ernst, Schirin; Amann, Wolfgang; Kaase, Hans-Jürgen; Banning, Ottmar; Voigt, Thomas; Grünert, Frank; Gürtler, Michael; Pferdmenges, Karin; van Treek, Heiko; Möller, Bernd; Weigel, Sybille; Jun Hassler, Normann; Mauer, Helmuth; Beckers, Erwin; Weber, Clemens-August; Hawash, Hana; Ladke, Dietrich; Labitzky, Gerlinde; Kunkel, Petra; Hartung, Wolfgang; Pomykaj, Thomas; Prokop, Heiun; Schleif, Thomas; Cascino, Luisa; Exner, Petra; Daelman, Eric; Dietrich, Aneas; Prasse, Thomas; Brundisch, Stefanie; Schipper, Ralf; Duderstaedt, Bernd; de Haan, Fokko; Schmidt-Reinwald, Astrid; Seidel, Peter; Schmitz, Joachim; Bülent, Ergec; Ja Pique, Pyoong; Ding, Roland; Eggeling, Thomas; Duderstaedt, Elvira; Ferchland, Hans-Peter; Kruth, Renate; Gralla, Dieter; Köhler, Angelika; Laborge, Joachim Rene; Hammer, Harald; Richter, Ilona; Sauldie, Happy; Valk-Denkema, Inge Van Der; van der Valk, Leo; Feely, John; Dunne, Liam; Cox, John; Doyle, Michael; O'Gorman, Mary; Kennedy, John; Maher, Brian; Forde, Derek; Harrington, Peter; Cronin, Brian; Coady, Anew; Craig, John; O'Dowd, Caroline; O'Doherty, Brian; O'Connor, Patrick; Ling, Roland; Perry, Majella; Crowley, James; Keaveney, Lynda; Townley, Eadaoin; O'Shea, Eamonn; Regan, Michael; Cunningham, Seamus; Bluett, Desmond; Whyte, Oliver; Casey, Michael; Ruane, Fergal; Fitzgerald, Eleanor; O'Beirn, Eugene; Faller, Eamonn; Moffatt, Sean; Coleman, Michael; Day, Brendan; Mcadam, Brendan; O'Neill, Daragh; Mac Mahon, Conor; Wheeler, Mark; Byrne, Sheila; Fulcher, Kieran; CAREY, Owen; O'Connell, Kieran; Keane, Jack; Almarsomi, Laith; Vaughan, Carl; O'Callaghan, Tom; Grufferty, Tadgh; Shanahan, Eamon; Crowley, Brendan; Moran, Joe; Cotter, Jeremy; Healy, Colin; Curtin, Tom; Dillon, Joe; Dennehy, Thomas; Murphy, Elaine; Kennedy, Michael; Coffey, Donal; Carroll, Paul O.; Oliver, Barry; Mccarthy, Shane; Joyce, Peter; O'Shea, Gerard; Apperloo, A. J.; Basart, D. C. G.; Bax, M.; Beysens, P. A. J.; Breed, J. G. S.; Derks, A.; Eijgenraam, J. W.; Hermann, J. P. R.; Janus, C. L.; Kaasjager, H. A. H.; Klomps, H. C.; Koole, M. A. C.; Koster, T.; Kroon, C.; Lieverse, A. G.; Massaar-Hagen, B. E. M.; Moghaddam, F.; Oldenburg-Ligtenberg, P. C.; Potter van Loon, B. J.; Stroes, E. S. G.; Twickler, Th B.; van Asperdt, F. G. M. H.; van Asseldonk, J. P. M.; van der Loos, T. L. J. M.; van der Velde, R. Y.; van der Vring, J. A. F.; van Dorp, W. T.; van Essen, G. G.; van Kalmthout, P. M.; van Liebergen, R. A. M.; van Wissem, S.; Waanders, H.; Withagen, A. J. A. M.; Andersen, Per Vidar Klemet; Andersen, Randi F.; Andersson, Egil; Arnstad, Asle; Belguendouz, Larbi; Birkeland, Inge Arve; Bjørkum, Kari; Bredvold, Thor; Brevig, Leif Harald; Buchman, Erik; Burkeland-Matre, Rune; Burski, Krzysztoft; Byre, Roald; Bø, Per Erik; Dahl, Erik; Duch, Anna; Duong, Khoa; Dvergsdal, Peter; Edvardsen, Magne; Ernø, Asbjørn; Fredwall, Svein Otto; Glasø, Morten; Glasø, Jan; Grini, Asbjørn; Hallaråker, Arne; Normann Hansen, Age Normann; Haugland, Helge Haugland; Henrichsen, Svein Høegh; Hestnes, Atle; Idehen, Norman I. E.; Jacobsen, Kristin Løland; Johansen, Ture; Johnsen, Roald; Jonasmo, Kåre; Kirknes, Svetalana; Kjetså, Arild; Kjaer, Peter; Knoph, Erik; Knutssøn, Carl; Koss, Arne; Kravtchenko, Oleg; Krogsæter, Dagfinn; Langaker, Kåre; Lind, Knut W.; Lund, Kjell Rømyhr; Madsbu, Sverre; Mehlum, Yvonne E. Mazurek; Moon, Philipp; Movafagh, Aram; Myhrer, Kurt; Nørager, Dan Michael; Ore, Stephan; Rafat, Hooshang B.; Rød, Reinert; Schmidt-Melbye, Torgeir; Singh, Navneet; Singsås, Tore; Skjelvan, Gunnar; Smet, Arthur; Staalesen, Staale; Storeheier, Espen; Storhaug, Sidsel; Storm-Larsen, Ane; Sundby, Jon Eivind; Syverstad, Dag Eivind; Sørensen, Anne Sissel; Torjusen, Trygve B.; Torkelsen, Arne; Tunby, Jan Reidar; Vanberg, Pål Johan; Vevatne, Audun; Vikse, Arild; Wahlstrøm, Viktor; Walaas, Kirsten; Walløe, Arne Eyolf; Wear-Hansen, Hans-Gunnar; Ole Ystgaard, Ole Aneas; Zimmermann, Birgit; Øvsthus, Knut; Aião, Julio; Albuquerque, Mario; Alves, Fernando; Esteves, Antonio; Amaral, Maria Fatima; Amaral, Fátima; Amorim, Helena; Anade, Benilde; Anade, Maria Benilde; Antonio, Godinho; Araujo, Francisco; Arriaga, Antonio; Baeta, Sonia; Afonso, Francisca Banha; Beato, Vitor; Beirão, Paula; Martins, Ausenda Belo; Bernardes, Jose; Botas, Luis; Baeta, Antonio; Ramos, Manuel Braga; Brandão, Peo; Brandão, Antonio G.; Brandão, Antonio; Raposo, Antonio Caetano; Carrilho, Francisco; Carvalho, Isabel; Carvalho, Patricia; Castel-Branco, Ana; Castellano, Maria Desamparados; Corredoura, Ana; Corredoura, Ana Sofia; Costa, Vitor; Coutinho, João; Crujo, Francisco; Cunha, Damião; Dias, Manuela; Fernandes, Maria Emilia; Ferreira, Gustavo; Ferreira, Dirce; Ferreira, Jorge; Ferreira, Antonio M.; Fonseca, Antonio; Freitas, Paula; Gago, Amandio; Galego, Rosa; Garrett, Antonio Viriato; Gavina, Cristina; Simões, José Geraldes; Gomes, Maria Fatima; Gomes, Norberto; Gomez, Brigitte; Graça, Peo; Gravato, Antonio; Guedes, Nuno Filipe; Guerra, Fernanda; Issa, Custódio; João, Isabel Fernandes; João, Isabel; Jorge, Vasco; Leite, Maria Salome; Lousada, Nuno; Macedo, Filipe M.; Madeira Lopes, João; Magalhães, Jorge; Marinho, Jose Carlos; Marques, Carlos; Marques, Jose Augusto; Marques Ferreira, Antonio; Martins, Jose Carlos; Martins, J. Belo; Matos, Alice; Melo, Miguel; Miguel, Antonia; Monteiro, Filomena; Monteiro, Francisco; Monteiro, Filomena B.; Sarmento, João Morais; Morato Sá, Maria José; Mota, Joana; Moura, Luis; Moura, Brenda; Neves, Lena; Neves, Celestino; Oliveira, Maria; Oliveira Ramos, Manuel; Osorio, Ramos; Pacheco, Joao; Palma, Isabel; Peixoto, Maria Cristina; Pereira, Helder; Pestana, João; Pignatelli, Duarte; Pinho, Hernani; Puig, Jorge; Raindo, Maria; Ramos, Helena; Rebelo, Marta; Roigues, Antonio; Roigues, Alvaro; Roigues, Elisabete; Rola, José; Rovytchcva, Milena; Sa, João; Santos, Fernando; Santos, João Cesar; Sequeira Duarte, Joao; Serra E Silva, Polybio; Silva, Bernardino; Silva, Paula; Silva, Maria; Silva, Francisco; Silva, Dora; Silva, José; Silvestre, Isabel; Simões, Heleno; Soares, Manuela; Sousa, Nelson; Sousa, Antonio; Souto, Delfina; Teixeira, Esmeralda; Torres, Isabel; Valle, Tahydi; Ventura, Carlos; Vicente, Ana; Vieira, Muriel; Alfaro, Rafael; Alonso, Roigo; Alvarez, Juan Carlos; Allut, Germán; Amado, Jose A.; Ampuero, Javier; Angel, Luis Fernando; Antolín, Eduardo; Anton, Javier; Aranda, Jose Luis; Argimon, Jordi; Arques, Francesc; Arribas, Jose Peo; Arroya, Concepción; Arroyo, Jose Antonio; Auladell, Maria Antonia; Bajo, Julian; BALVIN, Alberto; Ballester, Jose Vicente; Barreda Glez, Maria Jesus; Becerra, Antonio; Bermejo, Juan Carlos; Bernacer, Luis; Besada, Ricardo; Blasco, Jesús; Bravo, Manuel; Bueno, Francisco Manuel; Campo, Ignacio; Carrasco, Jose Luis; Catalán, José Ignacio; Cobo, Jose; Coello, Ignacio; Combarro, Jesús; Contreras, Juan A.; Correa, Julian; Cortilla, Alberto; Cuatrecasas, Guillem; Chicharro, Sana; de Dios, Juan; de Los Arcos, Enrique; de Portugal, Jose; del Cañizo, Francisco; del Molino, Fatima; Díaz, Jose Luis; Domingo, Javier; Escobar, Carlos; Escoda, Jaume; Espinosa, Eugenio; Ester, Francisco; Fernandez, Antonio; Ferreiro, Manuel; Fondas, Jose Maria; Fraile, Angel Luis; Franco, Miguel; Fuentes, Francisco; Garcia, Jose Antonio; Garcia, Domingo; Garcia, Manuel Enrique; García, Luis; Garcia, Jesus; Gilabert, Rosa; Goiria, Begoña; Gomez, Purificación; Gomez-Calcerrada, David; Gonzalez, Manuel; Gonzalez, Jose Manuel; Guijarro, Carlos; Guirao Gujarro, Victor; Herrera, Carlos; Herrera, Maria Carmen; Herrero, Miguel; Ibarguren, Amaya; Irigoyen, Luis; Jimenez, Blas; Lamelas, Jose Antonio; Laplaza, Ismael; Laporta, Felix; Lazo, Victor; Leal, Mariano; Ledesma, Vicente; Lopez, Peo; Lopez, Pablo; Lopez, Alberto; López, Maria Jose; Lopez-Cepero, Eduardo; Lorenzo, Francisco; Lucena, Javier; Luquín, Rafael; Lloveras, Ariadna; Maceda, Teresa; Macia, Ramon; Marti, Cristina; Martin, Jose Maria; Martin, Isodoro; Martín Lesende, Iñaki; Martinez, Mercedes; Martinez, Juan Alberto; Martinez, Peo; Martinez, Angel; Mato, Fernando; Medel, Federico; Mederos, Ana Maria; Mediavilla, Javier; Mediavilla, Gregorio; Mestron, Antonio; Michans, Antonio; Millán, Jesús; Molina, Carlos; Monroy, Carmelo; Monte, Inés; Montes, Jose Maria; Morales, Clotilde; Morales, Francisco J.; Morata, Carmen; Mori, Carlos; Muñoz, Jaime; Muñoz, Maria Jose; Núnez, Julio; Nuñez, Alfonso; Ocaña, Fermin; Olaz, Fernando; Ollero Artigas, Anes; Ortega, Juan; Oteo, Olga; Pascual, Jose Maria; Paya, Jose Antonio; Pechuan, Joaquín; Penedo Suarez, Ramón; Perez, Eugenia; Pesquera, Carlos; Pia, Gonzalo; Piea, Maria; Pinilla, Martin; Pita, Alejano; Pose, Antonio; Prieto Díaz, Miguel Angel; Quesada, Carmen; Ramirez, Francisco; Ramirez, Carmen; Ramirez, Luisa; Reinares, Leonardo; Rey, Salvador; Ribas, Montse; Ridaura, Amparo; Ridocci, Francisco; Rigueiro, Peo; Rivera, Salomón; Robles, Antonio; Rodero, Estrella; Roiguez, Jose Angel; Romero, Fernando; Romero Hernandez, Franklin; Romeu, Regina; Rubio Buisán, Lorenzo; Salas, Fernando; Sánchez, Carlos; Sánchez, Jesus; Saponi, Jose Maria; Serres, Miguel; Suarez, Saturnino; Suarez, Carmen; Tato, Maria; Tebar, Francisco Javier; Toda, Maria Roca; Tofe, Santiago; Urdiain, Raquel; Vaamonde, Leopoldo; Valderrama, Javier; Vazquez, Jose Antonio; Velazquez, Osvaldo; Venell, Federico; Vilariño, Ruben; Villa, Maria Jesus; Villar, Maria Dolores; Zarauza, Jesus; Zuñiga, Manuel; Abab, Jose Luis; Abad, Eduardo; Abad, Rafael; Afonso, Carmen; Aguilar, Gerardo; Alberiche, Maria Del Pino; Alcolea, Rosa; Alegria, Eduardo; Almagro, Fátima; Almenara, Africa; Almenos, Maria Cruz; Alonso, Javier; Alvarez, Manuel; Ampudia, Javier; Andia, Victor Manuel; Anglada, Jordi; Aranda, Miguel Ángel; Arbelo, Lorenzo; Armengol, Francesc; Arnau, Asunción; Arrarte, Vicente; Arribas, Bienvenido; Artiñano, Yolanda; Avilés, Benjamín; Ayensa, Javier; Ballestar, Enric; Ballester, Javier; Barcelo, Bartolome; Barcena, Felix; Barranco, Mercedes; Barrena, Isabel; Barriales, Vicente; Barrot, Joan; Bartolome, Jose A.; Belmonte, Joan; Bellés, Amadeo; Benito, Josefina; Bernad, Antonio; Biendicho, Armando; Blanco, Rubén; Boix, Evangelina; Bonora, Carlos; Boxó, Jose Ramon; Brea, Angel; Caballero, Peo; Cabrera, Peo; Cabrero, Juan Jose; Calduch, Lourdes; Calero, Francisco; Calvo Garcia, Jose Javier; Camacho, Jose; Canales, Juan Jose; Caparros, Jorge; Carbonell, Francisco; Caro, Manuel; Castilla, Miguel Angel; Castillo, Luis; Cepero, Daniel; Cerdan, Miguel; Cimbora, Antonio; Civera, Miguel; Colchero, Justo; Comas Fuentes, Angel; Corpas, Clara; Corrales, Juan Antonio; Cotobal, Eusebio; Cruz, Carmen; Cruz, Inmaculada; de La Flor, Manuel D.; de Luis, Alberto; del Alamo, Alberto; del Rosario, Victor; Diego, Carlos; D'Lacoste, Marta; Doganis Peppas, Constantino; Dominguez, Jose Ramon; Durá, Francisco Javier; Durand, Jose L.; Ena, Javier; Encinas, Ana Rosa; Erdozain, Juan Peo; Escribano, Jose; Escriva, Blanca; Esteve, Eduardo; Facila, Lorenzo; Fenoll, Federico; Fernandez, Eugenio; Fernandez, Celia; Fernandez, Maria Jesus; Fernandez, Antonia; Fernandez, Jacinto; Fernandez, Severo; Fernandez, Jose Manuel; Fernandez, Jose Manuel Fernandez; Ferrer, Juan Carlos; Ferrer, Peo; Ferrer Bascuñana, Peo; Fierro, Maria Jose; Flores, Julio; Fuentes, Fernando; Fuertes, Jorge; Galgo, Alberto; Galvez, Angel; Gallego, Anea; Garcia, Maria Angeles; Garcia, Jose; Garcia, Maria Luisa; Garcia, Peo; Garcia, Javier; García, Francisco; Garrido, Nícolas Garrido; Gil, Manuel Gil; Ginés Gascón, Ramón; Godoy, Diego; Gomez, Carlos Manuel; Gonzalez, Miguel; Gonzalez, Rosa; Gonzalez, Rocío; Gonzalez, Enrique; Gonzalez, Juan Jose; Gonzalez, Joaquin; Gonzalez Huambos, Adan; Guerrero, Jordi; Guillen, Rosario; Guirao, Lorenzo; Gutierrez, Fernando; Gutierrez, Diego; Hernandez, Alberto; Hernandez, Antonio; Hernandis, Vicenta; Herrero, Jose Vicente; Herreros, Benjamin; Hevia Roiguez, Eduardo; Horgue, Antonio; Illan, Fatima; Inigo, Pilar; Ibrahim Jaber, Ali; Jimenez, Manuel; Jornet, Agusti; Juanola, Ester; Laguna, Alfonso; Latorre, Juan; Lebron, Jose Antonio; Lecube, Albert; Ledesma, Claudio; Ligorria, Cristina; Lima, Joan; López, Jose Enrique; Lopez, Manuel; López, José Antonio; López, Jaime; López, Isio; Lozano, Jose Vicente; Mangas, Miguel Angel; Mangas, Alipio; Manzano, Antonio; Maraver, Juan; Marco, Maria Dolores; Marchán, Enrique; Marchante, Francisco; Marin, Fernando; Marreo, Josefa Esther; Martin, Manuel; Martin, Alberto; Martin, Francisco Javier; Martinez, Antonio; Martinez, Guillermo; Martínez, Luis; Martinez Barselo, Antonio Pablo; Mas, Emili; Mascareño, Isabel; Mascarós, Enrique; Massa, Rita; Mazón, Pilar; Mediavilla, Juan Diego; Mena, Candido; Mendez, Jose; Mendez, Jose Maria; Mezquita Raya, Peo; Millan, Jose Maria; Millaruelo, Jose; Minguela, Ester; Miret, Pere; Molina, Mariano; Molina, Carmen; Montagud, Blanca; Montalban, Coral; Montiel, Angel; Montoro, Javier; Monze, Bernardo; Moreno, Francisco Luis; Morillas, Antonio; Moro, Jose Antonio; Moya, Ana; Muñiz, Ovidio; Muñoz, Manuel; Navarro, Vicente Luis; Nerin, Jesus; Nicolas, Ricardo; Nogueiras, Concepción; Ojeda, Benito; Olmerilla, Javier; Oller, Guillermo; Ortega, Antonio; Ortega, Manuel; Ortega, Miguel; Ortiz, Maria Jose; Otegui Alarduya, Luis; Palet, Jordi; Palomo, Jesus; Paytubí, Carlos; Peiro, Rafael; Pelaez, Carmen; Peña, Peo; Peñafiel, Javier; Perez, Antonia; Perez, Elvira; Perez, Tomas; Peso, Miguel; Pilar, Juan Manuel; Piñeiro, Carlos; Plaza, Jose Antonio; Polo, Noelia; Portal, Maria; Prieto, Jesus; Prieto, Luis; Prieto Novo, Manuel; Puñal, Peo; Quesada, Miguel; Quindimil, Jose Antonio; Rabade, Jose Manuel; Ramila Beraza, Luis Antonio; Ramirez, José Manuel; Ramos, Jose Antonio; Ramos, Francisco; Rayo, Manuel; Reixa Vizoso, Sol; Reyes, Antonio; Rico, Miguel Angel; Ripoll, Tomas; Rivera, Antonio; Robres, Mariano; Rodilla, Enrique; Roiguez, Miguel Angel; Roiguez, Zoilo Jesus; Roiguez, Carlos; Roiguez, Pilar; Roiguez, Melchor; Roiguez, Alfonso; Rojas, Domingo; Rosell, Luis; Rossignoli, Carlos; Rueda, Antonio; Rueda, Eloy; Ruix, Anes; Ruiz, Jose Antonio; Ruiz, Luis; Saban, Jose; Saez, Francisco Jose; Salleras, Narcis; Sánchez, Gerardo; Sanchez, Gloria; Sanchez, Angel; Sanfeliu, Josep Maria; Sangros Gonzalez, Javier; Santos, Francisco; Santus, Eufrosina; Sebastian, Alfredo; Seguro, Maria Eugenia; Selles, David; Serrano, Daniel; Serrano, Soledad; Serrano, Adalberto; Sestorain, Francisco; Solbes, Ruben; Soriano, Cristina; Suárez, Héctor; Surroca, Maria Luisa; Tarabini, Ada; Tarraga, Peo; Teixido, Eulalia; Terron, Raquel; Torres, Antonio; Tortosa, Jose Maria; Tortosa, Frederic; Valdés, Carmen; Valdés, Peo; Valiente, Jose Ignacio; Varo, Antonio; Vazquez, Enrique; Vázquez, Luis; Vela Ruiz de Morales, Jose Manuel; Vericat, Antonio; Vicioso, Peo; Vilaplana, Carlos; Villazón, Francisco; Lidia Viñas, Lidia Viñas; Zuagoitia, Jose Felix; Nörgaard, Faris; Dziamski, Ryszard; Haglund, Lars; Holm, Daniela; Sars, Mikael; Jagunic, Ivica; Östgård, Per; Kumlin, Lars; Jacobsson, Michael; Hamad, Yousef; Jäger, Wanje; Särhammar, Lars; Olsson, Anders; Boldt-Christmas, Antonina; Nyborg, Karin; Kjellström, Thomas; Ghazal, Faris; Wikström, Lene; Holby, Torulf; Bhiladvala, Pallonji; Kynde, Sara Maria; Eizyk, Enrique Julio; Tengblad, Anders; Christoffersson, Ole; Sjöström, Astrid; Kynde, Christian; Katzman, Per; Tenhunen, Anita; Lennermo, Klas; Lindholm, Carl-Johan; Löndahl, Magnus; Elfstrand, Aino; Grönlund-Brown, Inger; Ziedén, Bo; Minnhagen, Karin; Lindvall, Peter; Fant, Kristina; Kaczynski, Jacek; Wallmark, Anders; Wallén, Carl-Erik; Wallberg, Håkan; Grönquist, Lennart; Hansen, John Albert; Björkander, Inge; Timberg, Ingar; Rosenqvist, Ulf; Fries, Robert; Carlsson, Jan-Erik; Rautio, Aslak Tauno; Sjöberg, Lennart; Wirdby, Alexander; Höök, Peter; Larsson, Åsa; Bergström, Catharina Lysell; Jwayed, Addnan; Smolowicz, Adam; Lindman, Anne-Christine; Nilsson, Per; Tarrach, Gerrit; Carlsson, Ingolf; Wieloch, Mattias; Rindevall, Peter; Strömblad, Gunnar; Holmberg, Göran; Shahnazarian, Henrik; Melchior, Jan; Younan, Kamal; Hansson, Anders; Bjurklint, Dag; Borgencrantz, Bertil; Sjöström, Malin; Mullaart, Mikael; Munoz, Marjatta; Jakkola, Vallentina; Romot, Jaan; Dash, Rabinarayan; Magnusson, Jan-Olof; Ahmed, Saman; Jonsson, Christina; Pipkorn, Owe; Bray, Edward; Wolff, Aneas; Black, Iain; Head, Christopher; Allan, Anthony

    2011-01-01

    To assess the prevalence of persistent lipid abnormalities in statin-treated patients with diabetes with and without the metabolic syndrome. This was a cross-sectional study of 22,063 statin-treated outpatients consecutively recruited by clinicians in Canada and 11 European countries. Patient

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

    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

  5. Sustainability assessment of advanced wastewater treatment technologies

    Høibye, Linda; Clauson-Kaas, Jes; Wenzel, Henrik

    2007-01-01

    , which includes technical, economic and environmental aspects. The technical and economic assessment is performed on 5 advanced treatment technologies: sand filtration, ozone treatment, UV exclusively for disinfection of pathogenic microorganisms, Membrane Bioreactor (MBR), and UV in combination......As a consequence of the EU Water Framwork Directive, more focus is now on discharges of hazardous substances from wastewater treatment plants and sewers. Thus, many municipalities in Denmark may have to adopt to future advenced treatment technologies. This paper describes a holistic assessment...... with advanced oxidation. The technical assessment is based on 12 hazardous substances comprising heavy metals, organic pollutants, endocrine disruptors as well as pathogenic microorganisms. The environmental assessment is performed by life cycle assessment (LCA) comprising 9 of the specific hazardous substances...

  6. Sustainability assessment of advanced wastewater treatment technologies

    Høibye, Linda; Clauson-Kaas, Jes; Wenzel, Henrik

    2008-01-01

    , which includes technical, economical and environmental aspects. The technical and economical assessment is performed on 5 advanced treatment technologies: sand filtration, ozone treatment, UV exclusively for disinfection of pathogenic microorganisms, membrane bioreactor (MBR) and UV in combination......As a consequence of the EU Water Framework Directive more focus is now on discharges of hazardous substances from wastewater treatment plants and sewers. Thus, many municipalities in Denmark may have to adopt to future advanced treatment technologies. This paper describes a holistic assessment...... with advanced oxidation. The technical assessment is based on 12 hazardous substances comprising heavy metals, organic pollutants, endocrine disruptors as well as pathogenic microorganisms. The environmental assessment is performed by life cycle assessment (LCA) comprising 9 of the specific hazardous substances...

  7. Statin use is not associated with improved progression free survival in cetuximab treated KRAS mutant metastatic colorectal cancer patients: results from the CAIRO2 study.

    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.

  8. The importance of reaching lipid targets: statins and the prevention of atherosclerosis.

    Schwandt, P

    2003-06-01

    To help prevent the development of coronary heart disease (CHD), the European and NCEP guidelines have recommended target cholesterol levels for all individuals. Lifestyle changes are advocated for individuals not achieving these targets. Intervention with lipid-modifying agents may be required for patients at high risk of a cardiovascular event and statins are generally recognised as first-line therapy. Unfortunately, large numbers of patients at risk of cardiovascular events are not being treated to the guideline targets. Primary care physicians are in a good position to improve lipid management by assessing risk factors, implementing lipid management strategies, monitoring whether targets are being reached and amending treatment appropriately. Furthermore, by educating and motivating patients,primary care physicians may improve compliance with lifestyle changes and medication. These approaches may help more patients to achieve recommended lipid levels and prevent the development of cardiovascular disease.

  9. The demand for statin: the effect of copay on utilization and compliance.

    Thiebaud, Patrick; Patel, Bimal V; Nichol, Michael B

    2008-01-01

    Increasing drug costs in the US have prompted employers and insurers alike to turn to higher drug copays for cost containment. The effect of rising copays on compliance with statins (HMG-CoA reductase inhibitors) treatment has received surprisingly little attention in the applied literature. This paper uses pharmacy claims data from a commercially insured adult population to determine the effect of copay change on compliance at the individual level. Fixed effect logit and Poisson regressions estimate the effect of copays on monthly likelihood of high compliance and average monthly days of supply respectively. Higher copays reduce compliance among statin users, with less compliant patients responding more strongly to copay change than compliant patients. These results suggest that specific financial incentives given to less compliant patients could improve compliance with statin treatment at a relatively low cost. Copyright (c) 2007 John Wiley & Sons, Ltd.

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

    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.

  11. Improved Biochemical Outcomes With Statin Use in Patients With High-Risk Localized Prostate Cancer Treated With Radiotherapy

    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.

  12. Muscle symptoms in statin users, associations with cytochrome P450, and membrane transporter inhibitor use: a subanalysis of the USAGE study.

    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.

  13. Assessing mixed waste treatment technologies

    Berry, J.B.; Bloom, G.A.; Hart, P.W.

    1994-01-01

    The US Department of Energy (DOE) is responsible for the management and treatment of its mixed low-level wastes (MLLW). As discussed earlier in this conference MLLW are regulated under both the Resource Conservation and Recovery Act and various DOE orders. During the next 5 years, DOE will manage over 1,200,000 m 3 of MLLW and mixed transuranic (MTRU) waste at 50 sites in 22 states (see Table 1). The difference between MLLW and MTRU waste is in the concentration of elements that have a higher atomic weight than uranium. Nearly all of this waste will be located at 13 sites. More than 1400 individual mixed waste streams exist with different chemical and physical matrices containing a wide range of both hazardous and radioactive contaminants. Their containment and packaging vary widely (e.g., drums, bins, boxes, and buried waste). This heterogeneity in both packaging and waste stream constituents makes characterization difficult, which results in costly sampling and analytical procedures and increased risk to workers

  14. Brand Name Statin Prescribing in a Resident Ambulatory Practice: Implications for Teaching Cost-Conscious Medicine.

    Ryskina, Kira L; Pesko, Michael F; Gossey, J Travis; Caesar, Erica Phillips; Bishop, Tara F

    2014-09-01

    Several national initiatives aim to teach high-value care to residents. While there is a growing body of literature on cost impact of physicians' therapeutic decisions, few studies have assessed factors that influence residents' prescribing practices. We studied factors associated with intensive health care utilization among internal medicine residents, using brand name statin prescribing as a proxy for higher-cost care. We conducted a retrospective, cross-sectional analysis of statin prescriptions by residents at an urban academic internal medicine program, using electronic health record data between July 1, 2010, and June 30, 2011. For 319 encounters by 90 residents, patients were given a brand name statin in 50% of cases. When categorized into quintiles, the bottom quintile of residents prescribed brand name statins in 2% of encounters, while the top quintile prescribed brand name statins in 98% of encounters. After adjusting for potential confounders, including patient characteristics and supervising attending, being in the primary care track was associated with lower odds (odds ratio [OR], 0.38; P  =  .02; 95% confidence interval [CI], 0.16-0.86), and graduating from a medical school with an above-average hospital care intensity index was associated with higher odds of prescribing brand name statins (OR, 1.70; P  =  .049; 95% CI, 1.003-2.88). We found considerable variation in brand name statin prescribing by residents. Medical school attended and residency program type were associated with resident prescribing behavior. Future interventions should raise awareness of these patterns in an effort to teach high-value, cost-conscious care to all residents.

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

    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

  16. Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults.

    Mansi, Ishak; Frei, Christopher R; Wang, Chen-Pin; Mortensen, Eric M

    2015-11-01

    Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the long-term effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied. To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults. This was a retrospective cohort study. Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers. We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers. Outcomes assessed included new-onset diabetes, diabetic complications, and overweight/obesity. A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67-2.01), diabetes with complications (OR 2.50; 95 % CI 1.88-3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04-1.25). Secondary and sensitivity analyses demonstrated similar findings. Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.

  17. Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke.

    Heller, David J; Coxson, Pamela G; Penko, Joanne; Pletcher, Mark J; Goldman, Lee; Odden, Michelle C; Kazi, Dhruv S; Bibbins-Domingo, Kirsten

    2017-09-19

    Statins are effective in the primary prevention of atherosclerotic cardiovascular disease. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline expands recommended statin use, but its cost-effectiveness has not been compared with other guidelines. We used the Cardiovascular Disease Policy Model to estimate the cost-effectiveness of the ACC/AHA guideline relative to current use, Adult Treatment Panel III guidelines, and universal statin use in all men 45 to 74 years of age and women 55 to 74 years of age over a 10-year horizon from 2016 to 2025. Sensitivity analyses varied costs, risks, and benefits. Main outcomes were incremental cost-effectiveness ratios and numbers needed to treat for 10 years per quality-adjusted life-year gained. Each approach produces substantial benefits and net cost savings relative to the status quo. Full adherence to the Adult Treatment Panel III guideline would result in 8.8 million more statin users than the status quo, at a number needed to treat for 10 years per quality-adjusted life-year gained of 35. The ACC/AHA guideline would potentially result in up to 12.3 million more statin users than the Adult Treatment Panel III guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 68. Moderate-intensity statin use in all men 45 to 74 years of age and women 55 to 74 years of age would result in 28.9 million more statin users than the ACC/AHA guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 108. In all cases, benefits would be greater in men than women. Results vary moderately with different risk thresholds for instituting statins and statin toxicity estimates but depend greatly on the disutility caused by daily medication use (pill burden). At a population level, the ACC/AHA guideline for expanded statin use for primary prevention is projected to treat more people, to save more lives, and to cost less

  18. Exploitation of Aspergillus terreus for the Production of Natural Statins

    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.

  19. Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia

    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

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

    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.

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

    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...

  2. Atherogenic Lipoprotein Subfractions Determined by Ion Mobility and First Cardiovascular Events After Random Allocation to High-Intensity Statin or Placebo: The Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial.

    Mora, Samia; Caulfield, Michael P; Wohlgemuth, Jay; Chen, Zhihong; Superko, H Robert; Rowland, Charles M; Glynn, Robert J; Ridker, Paul M; Krauss, Ronald M

    2015-12-08

    Cardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo. In 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio [HR] per SD, 1.03; 95% confidence interval [CI], 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk. In JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and

  3. Effect of an increased dosage of statins on spinal degenerative joint disease: a retrospective cohort study.

    Cheng, Yuan-Yang; Kao, Chung-Lan; Lin, Shih-Yi; Chang, Shin-Tsu; Wei, Tz-Shiang; Chang, Shih-Ni; Lin, Ching-Heng

    2018-02-08

    It has been proven that statin can protect synovial joints from developing osteoarthritis through its anti-inflammatory effects. However, studies on the effect of statins on spinal degenerative joint diseases are few and limited to in vitro studies. Therefore, we investigated the relationship between the statin dosage and the development of spinal degenerative joint diseases. A retrospective cohort study. Patients registered in Taiwan National Health Insurance Research Database. Patients aged 40-65 years old from 2001 to 2010 were included. Those who received statin treatment before 2001, were diagnosed with spinal degenerative joint diseases or received any spinal surgery before 2004 or had any spinal trauma before 2011 were excluded. A total of 7238 statin users and 164 454 non-users were identified and followed up for the next 7 years to trace the development of spinal degenerative joint disease. The incident rate of spinal degenerative joint diseases and HRs among the groups treated with different statin dosages. A higher dosage of statins was associated with a significantly lower risk of developing spinal degenerative joint disease in patients with hypercholesterolaemia. Compared with the group receiving less than 5400 mg of a statin, the HR of the 11 900-28 000 mg group was 0.83 (95% CI 0.70 to 0.99), and that of the group receiving more than 28 000 mg was 0.81 (95% CI 0.68 to 0.97). Results of subgroup analysis showed a significantly lower risk in men, those aged 50-59 years and those with a monthly income less than US$600. Our study's findings clearly indicated that a higher dosage of statins can reduce the incidence of spinal degenerative joint disease in patients with hypercholesterolaemia, and it can be beneficial for people with a higher risk of spine degeneration. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise

  4. Lipid Treatment Assessment Project (L-TAP Study : a survey in 13 cities in Indonesia to evaluate the percentages of dyslipidemic patients achieving NCEP LDL-C target goals after treatment

    Rinambaan W.M. Kaligis

    2001-06-01

    Full Text Available Clinical trials have demonstrated significant benefit from low density lipoprotein cholesterol (LDL-C lowering for primary and secondary prevention of cardiovascular disease. In the US, it is well recognized that a substantial number of hypercholesterolemic patients were not treated to the LDL-C goals recommended by the National Cholesterol Education Program (NCEP guidelines. In 1996, the Indonesian Heart Association (PERKI has issued guidelines recommending goals for screening and lipid treatment in Indonesia adopted from NCEP guidelines; however, the frequency of undertreatment in Indonesia is not known. The objective of this study was to determine the percentage of patients treated with lipid-lowering therapy who reached LDL-C goals as defined by NCEP guidelines in routine clinical practice. This was a cross-sectional survey targeted physicians who regularly treated dyslipidemic patients in 13 cities in Indonesia. Participating doctors were asked on their awareness of NCEP guidelines and to complete the case record form (CRF of the enrolled patients. One-hundred and eighty-eight (188 out of four hundreds (400 physicians who were invited, have participated in this study. Among the evaluable 1420 CRF, 1082 patients received statins, 301 used fibrates, 14 patients used combination drugs, and 23 others received non-drug treatments only. Success rates on achieving target LDL-C in low-risk, high-risk, and CHD groups were 73.0 %, 43.6 %, and 14.8 %, respectively. Overall success rate in patients using statins was 55.1 %, while in low-risk group, high-risk group, and CHD patients, the success rates with statin were 77.8%, 50.1%, and 18.6 %, respectively. Atorvastatin showed the highest success rate (77.4 % if compared to other statins. Only 14 % of physicians were knowledgeable about the NCEP goals. Conclusion : A large number of dyslipidemic patients who were on lipid-lowering therapy were not achieving the recommended LDL-C target

  5. Motivational effects of coronary artery calcium scores on statin adherence and weight loss.

    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.

  6. Statins Reduces the Risk of Dementia in Patients with Late-Onset Depression: A Retrospective Cohort Study.

    Yang, Ya-Hsu; Teng, Hao-Wei; Lai, Yen-Ting; Li, Szu-Yuan; Lin, Chih-Ching; Yang, Albert C; Chan, Hsiang-Lin; Hsieh, Yi-Hsuan; Lin, Chiao-Fan; Hsu, Fu-Ying; Liu, Chih-Kuang; Liu, Wen-Sheng

    2015-01-01

    Patients with late-onset depression (LOD) have been reported to run a higher risk of subsequent dementia. The present study was conducted to assess whether statins can reduce the risk of dementia in these patients. We used the data from National Health Insurance of Taiwan during 1996-2009. Standardized Incidence Ratios (SIRs) were calculated for LOD and subsequent dementia. The criteria for LOD diagnoses included age ≥65 years, diagnosis of depression after 65 years of age, at least three service claims, and treatment with antidepressants. The time-dependent Cox proportional hazards model was applied for multivariate analyses. Propensity scores with the one-to-one nearest-neighbor matching model were used to select matching patients for validation studies. Kaplan-Meier curve estimate was used to measure the group of patients with dementia living after diagnosis of LOD. Totally 45,973 patients aged ≥65 years were enrolled. The prevalence of LOD was 12.9% (5,952/45,973). Patients with LOD showed to have a higher incidence of subsequent dementia compared with those without LOD (Odds Ratio: 2.785; 95% CI 2.619-2.958). Among patients with LOD, lipid lowering agent (LLA) users (for at least 3 months) had lower incidence of subsequent dementia than non-users (Hazard Ratio = 0.781, 95% CI 0.685-0.891). Nevertheless, only statins users showed to have reduced risk of dementia (Hazard Ratio = 0.674, 95% CI 0.547-0.832) while other LLAs did not, which was further validated by Kaplan-Meier estimates after we used the propensity scores with the one-to-one nearest-neighbor matching model to control the confounding factors. Statins may reduce the risk of subsequent dementia in patients with LOD.

  7. Statin-induced autoimmune necrotizing myositis

    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.

  8. Statins attenuate but do not eliminate the reverse epidemiology of total serum cholesterol in patients with non-ischemic chronic heart failure.

    Fröhlich, Hanna; Raman, Nandita; Täger, Tobias; Schellberg, Dieter; Goode, Kevin M; Kazmi, Syed; Grundtvig, Morten; Hole, Torstein; Cleland, John G F; Katus, Hugo A; Agewall, Stefan; Clark, Andrew L; Atar, Dan; Frankenstein, Lutz

    2017-07-01

    In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival - while statin usage is not. The impact of statin treatment on the "reverse epidemiology" of cholesterol is unclear. 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample. 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤3.6mmol/L), moderate (3.7-4.9mmol/L), high (4.8-6.2mmol/L), and very high (>6.2mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p<0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77-0.90, p<0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p<0.001). Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. A polymorphism in HLA-G modifies statin benefit in asthma

    Naidoo, D; Wu, A C; Brilliant, M H

    2015-01-01

    Several reports have shown that statin treatment benefits patients with asthma; however, inconsistent effects have been observed. The mir-152 family (148a, 148b and 152) has been implicated in asthma. These microRNAs suppress HLA-G expression, and rs1063320, a common SNP in the HLA-G 3'UTR that i...

  10. Statin-induced liver injury in an area endemic for hepatitis B virus infection: risk factors and outcome analysis.

    Wang, Li Yueh; Huang, Yi-Shin; Perng, Chin-Lin; Huang, Bryan; Lin, Han-Chieh

    2016-09-01

    Statin-induced liver injury (SILI) is quite rare, but may be severe. Little is known about the impact of chronic hepatitis B infection (CHBI) on SILI. We aimed to investigate the risk factors and outcome of SILI, with special reference to its interaction with CHBI. Patients with SILI were recruited from our hospital, and three-to-one drug-matched controls were randomly selected. The clinical data of the patients were then compared. A total of 108 patients with SILI and 324 controls were enrolled. The patients with SILI were both older and had a higher statin dose than the controls. There was no predilection of liver injury associated with the seven available statins. Among the SILI patients, there was no statistical difference between the baseline and peak liver enzyme tests, and latency and severity between hepatitis B carriers (n = 16) and non-carriers (n = 92). High dose of statin and age were the two independent risk factors of SILI (OR and 95% CI: 1.93, 1.08-3.35, P = 0.025, and 1.73, 1.07-2.80, P = 0.027, respectively). Permanent discontinuation of statin was noted in 50 (46.3%) patients with SILI due to severe SILI or recurrent hepatotoxicity after rechallenge of other statins. High dose of statin and old age may increase patient susceptibility to SILI; however, CHBI and abnormal baseline liver tests are not risk factors of SILI. Nonetheless, SILI is still worthy of notice, because nearly half of the overt cases discontinued statin treatment due to severe hepatotoxicity in this study. © 2016 The British Pharmacological Society.

  11. Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy.

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

    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.

  13. Statins: the holy grail of Abdominal Aortic Aneurysm (AAA) growth attenuation? A systematic review of the literature.

    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.

  14. Assessment and Treatment of Pain during Treatment of Buruli Ulcer.

    Janine de Zeeuw

    Full Text Available Buruli ulcer (BU is described as a relatively painless condition; however clinical observations reveal that patients do experience pain during their treatment. Knowledge on current pain assessment and treatment in BU is necessary to develop and implement a future guideline on pain management in BU.A mixed methods approach was used, consisting of information retrieved from medical records on prescribed pain medication from Ghana and Benin, and semi-structured interviews with health care personnel (HCP from Ghana on pain perceptions, assessment and treatment. Medical records (n = 149 of patients treated between 2008 and 2012 were collected between November 2012 and August 2013. Interviews (n = 11 were audio-taped, transcribed verbatim and qualitatively analyzed.In 113 (84% of the 135 included records, pain medication, mostly simple analgesics, was prescribed. In 48% of the prescriptions, an indication was not documented. HCP reported that advanced BU could be painful, especially after wound care and after a skin graft. They reported not be trained in the assessment of mild pain. Pain recognition was perceived as difficult, as patients were said to suppress or to exaggerate pain, and to have different expectations regarding acceptable pain levels. HCP reported a fear of side effects of pain medication, shortage and irregularities in the supply of pain medication, and time constraints among medical doctors for pain management.Professionals perceived BU disease as potentially painful, and predominantly focused on severe pain. Our study suggests that pain in BU deserves attention and should be integrated in current treatment.

  15. Statin and NSAID Use and Prostate Cancer Risk

    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

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

    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

  17. Statin Use and Decline in Gait Speed in Community-Dwelling Older Adults

    Lo-Ciganic, W. H.; Perera, S.; Gray, S. L.

    2015-01-01

    ObjectivesTo examine the association between statin use and objectively assessed decline in gait speed in community-dwelling older adults. DesignLongitudinal cohort study. SettingHealth, Aging and Body Composition (Health ABC) Study. ParticipantsTwo thousand five participants aged 70-79 at baseli...

  18. A survey of the FDA's AERS database regarding muscle and tendon adverse events linked to the statin drug class.

    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

  19. Hydroxymethylglutaryl-CoA Reductase Inhibitors in Older Persons with Acute Myocardial Infarction: Evidence for an Age–Statin Interaction

    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

  20. Statins prevent cognitive impairment after sepsis by reverting neuroinflammation, and microcirculatory/endothelial dysfunction.

    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

  1. Statins reduce the expressions of Tim-3 on NK cells and NKT cells in atherosclerosis.

    Zhang, Na; Zhang, Min; Liu, Ru-Tao; Zhang, Peng; Yang, Chun-Lin; Yue, Long-Tao; Li, Heng; Li, Yong-Kang; Duan, Rui-Sheng

    2018-02-15

    3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (statins) have an immuno-regulatory effect in addition to lowing-lipids. Accumulated evidence showed that the expressions of T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) on natural killer (NK) cells increased in atherosclerotic patients and animal models. In this study, 14 patients treated with rosuvastatin and 12 patients with atorvastatin for more than 3 months were included and 20 patients without statins treatment as control. Both statins treatment reduced the expressions of Tim-3 on NK cells and their subtypes, natural killer T (NKT) cells and CD3 + T cells, and increased the proportions of NKT cells among peripheral blood mononuclear cells, accompanied by the decreased levels of total cholesterol, low density lipoprotein, and increased ratios of high density lipoprotein to cholesterol. These may contribute to the functions of statins in the treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Hypothyroidism as a risk factor for statin intolerance.

    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.

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

    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.

  4. The Role of Statins in Disease Modification and Cardiovascular Risk in Rheumatoid Arthritis

    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.

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

    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.

  6. Rising statin use and effect on ischemic stroke outcome

    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.

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

    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.

  8. Gemfibrozil in Combination with Statins-Is It Really Contraindicated?

    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.

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

    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....

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

    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.

  11. Understanding Statin Non-Adherence: Knowing Which Perceptions and Experiences Matter to Different Patients.

    Hans Wouters

    Full Text Available Non-adherence to statins is substantial and is associated with numerous perceptions and experiences. However, time limits in clinical practice constrain in depth explorations of these perceptions and experiences.To propose and examine a strategy aimed at an efficient assessment of a wide array of perceptions and experiences regarding the efficacy, side effects, and practical problems of statins. Furthermore, to assess associations between this wide array of experiences and perceptions and non-adherence and to examine whether patients' 'perceived self-efficacy' moderated these associations.Patients were recruited through community pharmacies. A wide array of specific patient perceptions and experiences was efficiently assessed using the electronic Tailored Medicine Inventory that allows people to skip irrelevant questions. Adherence was measured through self-report and pharmacy refill data.Of the two-hundred twenty-nine patients who participated (mean age 63.9, standard deviation 10.2, 40%-70% doubted the necessity of or lacked knowledge about the efficacy of statins, 20%-35% of the patients were worried about joint and muscle side effects or had experienced these, and 23% had encountered practical problems regarding information about statins, intake of tablets, the package, or the blister. Experiencing more practical problems was associated with increased unintentional non-adherence (Odds ratio 1.54, 95%CI:1.13-2.10, P < 0.01, whereas worrying about side effects was associated with increased intentional non-adherence (Odds ratio 1.90, 95%CI:1.17-3.08, P < 0.01. Higher 'perceived self-efficacy' did not moderate these associations.Insight into patients' specific barriers with regard to appropriate statin use may reveal personal reasons for being non-adherent. The Tailored Medicine Inventory is a promising tool to devise individualized intervention strategies aimed at improving adherence by the clinician-patient alliance.

  12. Statin use before diabetes diagnosis and risk of microvascular disease

    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

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

    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. Statin use and vitreoretinal surgery: Findings from a Finnish population-based cohort study.

    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.

  15. A randomized trial of coenzyme Q10 in patients with confirmed statin myopathy.

    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.

  16. Statin Eligibility and Outpatient Care Prior to ST-Segment Elevation Myocardial Infarction.

    Miedema, Michael D; Garberich, Ross F; Schnaidt, Lucas J; Peterson, Erin; Strauss, Craig; Sharkey, Scott; Knickelbine, Thomas; Newell, Marc C; Henry, Timothy D

    2017-04-12

    The impact of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines on statin eligibility in individuals otherwise destined to experience cardiovascular disease (CVD) events is unclear. We analyzed a prospective cohort of consecutive ST-segment elevation myocardial infarction (STEMI) patients from a regional STEMI system with data on patient demographics, low-density lipoprotein cholesterol levels, CVD risk factors, medication use, and outpatient visits over the 2 years prior to STEMI. We determined pre-STEMI eligibility according to American College of Cardiology/American Heart Association guidelines and the prior Third Report of the Adult Treatment Panel guidelines. Our sample included 1062 patients with a mean age of 63.7 (13.0) years (72.5% male), and 761 (71.7%) did not have known CVD prior to STEMI. Only 62.5% and 19.3% of individuals with and without prior CVD were taking a statin before STEMI, respectively. In individuals not taking a statin, median (interquartile range) low-density lipoprotein cholesterol levels in those with and without known CVD were low (108 [83, 138]  mg/dL and 110 [87, 133] mg/dL). For individuals not taking a statin, only 38.7% were statin eligible by ATP III guidelines. Conversely, 79.0% would have been statin eligible according to American College of Cardiology/American Heart Association guidelines. Less than half of individuals with (49.2%) and without (41.1%) prior CVD had seen a primary care provider during the 2 years prior to STEMI. In a large cohort of STEMI patients, application of American College of Cardiology/American Heart Association guidelines more than doubled pre-STEMI statin eligibility compared with Third Report of the Adult Treatment Panel guidelines. However, access to and utilization of health care, a necessity for guideline implementation, was suboptimal prior to STEMI. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  17. Consequences of succinylcholine administration to patients using statins.

    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.

  18. Statins, fibrates, nicotinic acid, cholesterol absorption inhibitors, anion-exchange resins, omega-3 fatty acids: which drugs for which patients?

    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.

  19. Non-response to (statin) therapy

    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....

  20. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

    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.

  1. Statins improve the resolution of established murine venous thrombosis: reductions in thrombus burden and vein wall scarring.

    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.

  2. Adherence and Persistence Among Statin Users Aged 65 Years and Over: A Systematic Review and Meta-analysis.

    Ofori-Asenso, Richard; Jakhu, Avtar; Zomer, Ella; Curtis, Andrea J; Korhonen, Maarit Jaana; Nelson, Mark; Gambhir, Manoj; Tonkin, Andrew; Liew, Danny; Zoungas, Sophia

    2018-05-09

    Older people (aged ≥ 65 years) have distinctive challenges with medication adherence. However, adherence and persistence patterns among older statin users have not been comprehensively reviewed. As part of a broader systematic review, we searched Medline, Embase, PsycINFO, CINAHL, Database of Abstracts of Reviews of Effects, CENTRAL, and the National Health Service Economic Evaluation Database through December 2016 for English articles reporting adherence and/or persistence among older statin users. Data were analyzed via descriptive methods and meta-analysis using random-effect modeling. Data from more than 3 million older statin users in 82 studies conducted in over 40 countries were analyzed. At 1-year follow-up, 59.7% (primary prevention 47.9%; secondary prevention 62.3%) of users were adherent (medication possession ratio [MPR] or proportion of days covered [PDC] ≥ 80%). For both primary and secondary prevention subjects, 1-year adherence was worse among individuals aged more than 75 years than those aged 65-75 years. At 3 and ≥10 years, 55.3% and 28.4% of users were adherent, respectively. The proportion of users persistent at 1-year was 76.7% (primary prevention 76.0%; secondary prevention 82.6%). Additionally, 68.1% and 61.2% of users were persistent at 2 and 4 years, respectively. Among new statin users, 48.2% were nonadherent and 23.9% discontinued within the first year. The proportion of statin users who were adherent based on self-report was 85.5%. There is poor short and long term adherence and persistence among older statin users. Strategies to improve adherence and reduce discontinuation are needed if the intended cardiovascular benefits of statin treatment are to be realized.

  3. Clinical characteristics and usage of statins in patients with stable ischemic heart disease referred for angiography or coronary artery bypass grafting

    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

  4. Statins attenuate polymethylmethacrylate-mediated monocyte activation.

    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.

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

    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

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

    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.

  7. Life cycle assessment of electronic waste treatment.

    Hong, Jinglan; Shi, Wenxiao; Wang, Yutao; Chen, Wei; Li, Xiangzhi

    2015-04-01

    Life cycle assessment was conducted to estimate the environmental impact of electronic waste (e-waste) treatment. E-waste recycling with an end-life disposal scenario is environmentally beneficial because of the low environmental burden generated from human toxicity, terrestrial ecotoxicity, freshwater ecotoxicity, and marine ecotoxicity categories. Landfill and incineration technologies have a lower and higher environmental burden than the e-waste recycling with an end-life disposal scenario, respectively. The key factors in reducing the overall environmental impact of e-waste recycling are optimizing energy consumption efficiency, reducing wastewater and solid waste effluent, increasing proper e-waste treatment amount, avoiding e-waste disposal to landfill and incineration sites, and clearly defining the duties of all stakeholders (e.g., manufacturers, retailers, recycling companies, and consumers). Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Use of statins and beta-blockers after acute myocardial infarction according to income and education

    Rasmussen, Jeppe Nørgaard; Gislason, Gunnar H; Rasmussen, Søren

    2007-01-01

    OBJECTIVE: To study the initiation of and long-term refill persistency with statins and beta-blockers after acute myocardial infarction (AMI) according to income and education. DESIGN AND SETTING: Linkage of individuals through national registers of hospitalisations, drug dispensation, income...... and education. PARTICIPANTS: 30 078 patients aged 30-74 years surviving first hospitalisation for AMI in Denmark between 1995 and 2001. MAIN OUTCOME MEASURES: Initiation of statin or beta-blocker treatment (out-patient claim of prescriptions within 6 months of discharge) and refill persistency (first break.......66-0.82) and medium (HR 0.82; 95% CI 0.74-0.92) income compared with low income, whereas there was a trend in the opposite direction concerning a break in beta-blocker treatment. There was no gradient in re-initiation of treatment. CONCLUSION: Patients with low compared with high income less frequently initiated...

  9. The relationship between statins and breast cancer prognosis varies by statin type and exposure time: a meta-analysis.

    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

  10. Life cycle assessment of electronic waste treatment

    Hong, Jinglan; Shi, Wenxiao; Wang, Yutao; Chen, Wei; Li, Xiangzhi

    2015-01-01

    Highlights: • Life cycle assessment of electronic waste recycling is quantified. • Key factors for reducing the overall environmental impact are indentified. • End-life disposal processes provide significant environmental benefits. • Efficiently reduce the improper disposal amount of e-waste is highly needed. • E-waste incineration can generate significant environmental burden. - Abstract: Life cycle assessment was conducted to estimate the environmental impact of electronic waste (e-waste) treatment. E-waste recycling with an end-life disposal scenario is environmentally beneficial because of the low environmental burden generated from human toxicity, terrestrial ecotoxicity, freshwater ecotoxicity, and marine ecotoxicity categories. Landfill and incineration technologies have a lower and higher environmental burden than the e-waste recycling with an end-life disposal scenario, respectively. The key factors in reducing the overall environmental impact of e-waste recycling are optimizing energy consumption efficiency, reducing wastewater and solid waste effluent, increasing proper e-waste treatment amount, avoiding e-waste disposal to landfill and incineration sites, and clearly defining the duties of all stakeholders (e.g., manufacturers, retailers, recycling companies, and consumers)

  11. Life cycle assessment of electronic waste treatment

    Hong, Jinglan, E-mail: hongjing@sdu.edu.cn [Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Jinan 250100 (China); Shandong University Climate Change and Health Center, Public Health School, Shandong University, Jinan 250012 (China); Shi, Wenxiao [Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Jinan 250100 (China); Wang, Yutao [School of Life Science, Shandong University, Shanda South Road 27, Jinan 250100 (China); Chen, Wei [Shandong Provincial Key Laboratory of Water Pollution Control and Resource Reuse, School of Environmental Science and Engineering, Shandong University, Jinan 250100 (China); Li, Xiangzhi, E-mail: xiangzhi@sdu.edu.cn [School of Medicine, Shandong University, Jinan 250012 (China)

    2015-04-15

    Highlights: • Life cycle assessment of electronic waste recycling is quantified. • Key factors for reducing the overall environmental impact are indentified. • End-life disposal processes provide significant environmental benefits. • Efficiently reduce the improper disposal amount of e-waste is highly needed. • E-waste incineration can generate significant environmental burden. - Abstract: Life cycle assessment was conducted to estimate the environmental impact of electronic waste (e-waste) treatment. E-waste recycling with an end-life disposal scenario is environmentally beneficial because of the low environmental burden generated from human toxicity, terrestrial ecotoxicity, freshwater ecotoxicity, and marine ecotoxicity categories. Landfill and incineration technologies have a lower and higher environmental burden than the e-waste recycling with an end-life disposal scenario, respectively. The key factors in reducing the overall environmental impact of e-waste recycling are optimizing energy consumption efficiency, reducing wastewater and solid waste effluent, increasing proper e-waste treatment amount, avoiding e-waste disposal to landfill and incineration sites, and clearly defining the duties of all stakeholders (e.g., manufacturers, retailers, recycling companies, and consumers)

  12. The role of acid-base imbalance in statin-induced myotoxicity.

    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

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

    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

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

    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

  15. Thermodynamic and Structure Guided Design of Statin Based Inhibitors of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase

    Sarver, Ronald W.; Bills, Elizabeth; Bolton, Gary; Bratton, Larry D.; Caspers, Nicole L.; Dunbar, James B.; Harris, Melissa S.; Hutchings, Richard H.; Kennedy, Robert M.; Larsen, Scott D.; Pavlovsky, Alexander; Pfefferkorn, Jeffrey A.; Bainbridge, Graeme (Pfizer)

    2008-10-02

    Clinical studies have demonstrated that statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) inhibitors, are effective at lowering mortality levels associated with cardiovascular disease; however, 2--7% of patients may experience statin-induced myalgia that limits compliance with a treatment regimen. High resolution crystal structures, thermodynamic binding parameters, and biochemical data were used to design statin inhibitors with improved HMGR affinity and therapeutic index relative to statin-induced myalgia. These studies facilitated the identification of imidazole 1 as a potent (IC{sub 50} = 7.9 nM) inhibitor with excellent hepatoselectivity (>1000-fold) and good in vivo efficacy. The binding of 1 to HMGR was found to be enthalpically driven with a {Delta}H of -17.7 kcal/M. Additionally, a second novel series of bicyclic pyrrole-based inhibitors was identified that induced order in a protein flap of HMGR. Similar ordering was detected in a substrate complex, but has not been reported in previous statin inhibitor complexes with HMGR.

  16. Muscular fixing of the H.M.D.P. {sup 99m}Tc induced by a statin, rosuvastatin or crestor: clinical case; Fixation musculaire du HMDP Tc99m induite par une statine, la rosuvastatine ou Crestor: cas clinique

    Bourahla, K.; Hassler, S.; Schneegans, O.; Gyen, L.N. [CLCC Paul-Strauss, Service de medecine nucleaire, 67 - Strasbourg (France)

    2010-07-01

    Myositis induced by statins in treatment for hypercholesterolemia is a special clinical entity that may be encountered during an exploration by bone scintigraphy. We present the case of a muscle fixing observed in bone scan in a patient treated with rosuvastatin (Crestor). Muscular extra bone fixing of hydroxy-methane diphosphonate (H.M.D.P.) {sup 99m}T in patients referred for staging of prostate carcinoma, patients sometimes also treated for high cholesterol may be iatrogenic due to taking statins. A simple history may then allow its identification, although it remains asymptomatic. (N.C.)

  17. High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

    Wang, Le; Peng, Pingan; Zhang, Ou; Xu, Xiaohan; Yang, Shiwei; Zhao, Yingxin; Zhou, Yujie

    2014-01-01

    Background Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention. Methods We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment. Results Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; Pstatin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious. Conclusions High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for

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

    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. Steroids and statins: an old and a new anti-inflammatory strategy compared.

    Vukovic, Petar M; Maravic-Stojkovic, Vera R; Peric, Miodrag S; Jovic, Miomir Dj; Cirkovic, Milan V; Gradinac, Sinisa Dj; Djukanovic, Bosko P; Milojevic, Predrag S

    2011-01-01

    This study compared the anti-inflammatory effects of methylprednisolone (MP) and atorvastatin and analysed their influences on clinical variables in patients undergoing coronary revascularization. Ninety patients with compromised left ventricular ejection fraction (≤30%) undergoing elective coronary surgery were equally randomized to one of three groups: statin group, treatment with atorvastatin (20 mg/day) 3 weeks before surgery; methylprednisolone group, a single shot of methylpredniosolone (10mg/kg); and control group. Postoperative IL-6 was higher in the control group when compared to the methylprednisolone and statin groups (patrial fibrilation rate and reduced ICU stay (patrial fibrilation rate and reduced ICU stay in patients with significantly impaired cardiac function undergoing coronary revascularization. Treatment with methylprednisolone was associated with less inotropic support requirements and reduced mechanical ventilation time.

  20. Relationship of C-reactive protein, metabolic syndrome and diabetes mellitus: potential role of statins.

    Nash, David T

    2005-12-01

    Atherosclerosis and the metabolic derangements of insulin resistance, metabolic syndrome and diabetes mellitus are all associated with underlying inflammatory processes. C-reactive protein (CRP), a marker of inflammation, has been shown to be a strong independent predictor of vascular events. It adds to cardiovascular disease risk at all levels of low-density-lipoprotein cholesterol and Framingham risk scores, and elevated levels are also associated with increasing severity of the metabolic syndrome. The development of a simple, stable, noninvasive test to measure high-sensitivity CRP has provided a clinical tool that may have an important role in the identification and assessment of individuals likely to develop cardiovascular or metabolic disease. The role of CRP in predicting cardiovascular risk is less clear in African Americans, however, than in white populations. Statins and thiazolidinediones are being investigated for their potential role in the prevention and treatment of the inflammatory processes involved in the metabolic syndrome and cardiovascular disease. In the future, assessment of CRP levels may contribute importantly to clinical decision-making in reducing cardiovascular risk.

  1. Technological advances and proteomic applications in drug discovery and target deconvolution: identification of the pleiotropic effects of statins.

    Banfi, Cristina; Baetta, Roberta; Gianazza, Erica; Tremoli, Elena

    2017-06-01

    Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics to the definition of the pharmacological profile of statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases (CVDs). Statins act by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus reducing cholesterol biosynthesis and consequently enhancing the clearance of low-density lipoproteins from the blood; however, HMG-CoA reductase inhibition can result in a multitude of additional effects beyond lipid lowering, known as 'pleiotropic effects'. The case of statins highlights the unique contribution of proteomics to the target profiling of a drug molecule. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    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 ...

  3. Price and utilisation differences for statins between four countries.

    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.

  4. Statin drug-drug interactions in a Romanian community pharmacy.

    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.

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

    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 ...

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

    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.

  7. Disappearance of statin following serum-stimulated cell cycle entry

    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

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

    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...

  9. Cardiovascular Risk Stratification and Statin Eligibility Based on the Brazilian vs. North American Guidelines on Blood Cholesterol Management.

    Cesena, Fernando Henpin Yue; Laurinavicius, Antonio Gabriele; Valente, Viviane A; Conceição, Raquel D; Santos, Raul D; Bittencourt, Marcio S

    2017-06-01

    The best way to select individuals for lipid-lowering treatment in the population is controversial. In healthy individuals in primary prevention: to assess the relationship between cardiovascular risk categorized according to the V Brazilian Guideline on Dyslipidemia and the risk calculated by the pooled cohort equations (PCE); to compare the proportion of individuals eligible for statins, according to different criteria. In individuals aged 40-75 years consecutively submitted to routine health assessment at one single center, four criteria of eligibility for statin were defined: BR-1, BR-2 (LDL-c above or at least 30 mg/dL above the goal recommended by the Brazilian Guideline, respectively), USA-1 and USA-2 (10-year risk estimated by the PCE ≥ 5.0% or ≥ 7.5%, respectively). The final sample consisted of 13,947 individuals (48 ± 6 years, 71% men). Most individuals at intermediate or high risk based on the V Brazilian Guideline had a low risk calculated by the PCE, and more than 70% of those who were considered at high risk had this categorization because of the presence of aggravating factors. Among women, 24%, 17%, 4% and 2% were eligible for statin use according to the BR-1, BR-2, USA-1 and USA-2 criteria, respectively (p valores para os homens foram 75%, 58%, 31% e 17% (p < 0,01). Oitenta e cinco por cento das mulheres e 60% dos homens elegíveis para estatina pelo critério BR-1 não seriam candidatos pelo critério EUA-1. Comparada à diretriz norte-americana, a V Diretriz Brasileira considera uma proporção substancialmente maior da população como elegível para estatina em prevenção primária. Isso se relaciona com discrepâncias entre o risco estratificado pela diretriz brasileira e o calculado pelas PCE, particularmente devido à reclassificação de risco baseada em fatores agravantes.

  10. Hyperlipidemia and statins use for the risk of new-onset anxiety/depression in patients with head and neck cancer: A population-based study.

    Huang, Chung-I; Lin, Li-Ching; Tien, Hung-Cheng; Que, Jenny; Ting, Wei Chen; Chen, Po-Chun; Wu, Hsin-Min; Ho, Chung-Han; Wang, Jhi-Joung; Wang, Ren-Hong; Yang, Ching-Chieh

    2017-01-01

    Anxiety/depression is common among patients with head and neck cancer (HNC), and can negatively affect treatment compliance and outcome. The aim of this study was to assess the association between hyperlipidemia and the risk of new-onset anxiety/depression after the diagnosis of HNC and the influence of administering statins. A matched longitudinal cohort study of 1632 subjects (408 HNC patients with preexisting hyperlipidemia and 1224 age- and sex-matched HNC patients without hyperlipidemia) was included and analyzed by using data from Taiwan's National Health Insurance Research Database from January 1996 to December 2012. The incidence and hazard ratios (HRs) for the development of new-onset anxiety/depression were examined between the two groups. Cox proportional hazard regression was applied to estimate the relative risks of anxiety/depressive disorders adjusted for potential confounding factors. To estimate the risks of anxiety/depression in different sub-groups, a stratified analysis was also used. HNC patients with preexisting hyperlipidemia had a higher risk for comorbidities such as hypertension, diabetes mellitus, and cardiovascular disease (P anxiety/depression in the HNC patients with preexisting hyperlipidemia was also significantly higher than that among patients without hyperlipidemia (10.78% vs 7.27%, respectively; P = 0.03). A Cox regression model revealed that preexisting hyperlipidemia was an independent risk factor for anxiety/depression (aHR, 1.96; 95% CI, 1.30-2.94). Statins use was protective against anxiety/depression among HNC patients with hyperlipidemia (aHR, 0.85; 95% CI, 0.46-1.57), especially for individuals older than 65 years and for females. Preexisting hyperlipidemia was associated with increased risk of new-onset anxiety/depression in the HNC patients. Statins use for HNC patients with hyperlipidemia could decrease the risk of anxiety/depression, especially for those older than 65 years and for female patients.

  11. End points and assessments in esthetic dental treatment.

    Ishida, Yuichi; Fujimoto, Keiko; Higaki, Nobuaki; Goto, Takaharu; Ichikawa, Tetsuo

    2015-10-01

    There are two key considerations for successful esthetic dental treatments. This article systematically describes the two key considerations: the end points of esthetic dental treatments and assessments of esthetic outcomes, which are also important for acquiring clinical skill in esthetic dental treatments. The end point and assessment of esthetic dental treatment were discussed through literature reviews and clinical practices. Before designing a treatment plan, the end point of dental treatment should be established. The section entitled "End point of esthetic dental treatment" discusses treatments for maxillary anterior teeth and the restoration of facial profile with prostheses. The process of assessing treatment outcomes entitled "Assessments of esthetic dental treatment" discusses objective and subjective evaluation methods. Practitioners should reach an agreement regarding desired end points with patients through medical interviews, and continuing improvements and developments of esthetic assessments are required to raise the therapeutic level of esthetic dental treatments. Copyright © 2015 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  12. Relative safety profiles of high dose statin regimens

    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

  13. Changes in muscle strength in patients with statin myalgia.

    Panza, Gregory A; Taylor, Beth A; Roman, William; Thompson, Paul D

    2014-10-15

    Statins can produce my