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Sample records for statin stemi trial

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

    LENUS (Irish Health Repository)

    Sattar, Naveed

    2010-02-27

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 We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes.

  2. Statins in heart failure: do we need another trial?

    OpenAIRE

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

    2013-01-01

    Kwadwo Osei Bonsu, Amudha Kadirvelu, Daniel Diamond ReidpathSchool of Medicine and Health Sciences, Monash University Sunway Campus, Bandar Sunway, MalaysiaAbstract: Statins lower serum cholesterol and are employed for primary and secondary prevention of cardiovascular events. Clinical evidence from observational studies, retrospective data, and post hoc analyses of data from large statin trials in various cardiovascular conditions, as well as small scale randomized trials, suggest survival a...

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

    Science.gov (United States)

    Golomb, Beatrice A.; Dimsdale, Joel E.; Koslik, Hayley J.; Evans, Marcella A.; Lu, Xun; Rossi, Steven; Mills, Paul J.; Criqui, Michael H.

    2015-01-01

    -cutoffs (≥50 or ≥55). Significance was observed separately for simvastatin. The aggression-increase in women on statins was stronger in those with low baseline aggression (N=175) β=0.84(SE=0.30)P=0.006. No statin effect on whole blood serotonin was observed; and serotonin-change did not predict aggression-change. Conclusion Statin effects on aggression differed by sex and age: Statins generally decreased aggression in men; and generally increased aggression in women. Both findings were selectively prominent in participants with low baseline aggression – bearing lower change-variance, rendering an effect more readily evident. Trial Registration Clinicaltrials.gov NCT00330980 PMID:26132393

  4. Ongoing clinical trials of the pleiotropic effects of statins

    Directory of Open Access Journals (Sweden)

    Jean Davignon

    2005-04-01

    Full Text Available Jean Davignon1, Lawrence A Leiter21Clinical Research Institute of Montreal, Montreal, QC, Canada; 2Division of Endocrinology and Metabolism, St Michael’s Hospital, Toronto, ON, CanadaBackground: The multiple effects (ie, pleiotropic effects of statins have received increasing recognition and may have clinical applicability across a broad range of cardiovascular and noncardiovascular conditions. Objective: To determine the relevance and significance of ongoing clinical trials of the pleiotropic effects of statins, focusing on nonlipid effects. Method: Ongoing trials were identified through personal communication, reports presented at scientific meetings (2000–2004, and queries made to AstraZeneca, Bristol-Myers Squibb Co, Merck & Co, Novartis, and Pfizer, manufacturers of the currently marketed statins. Published trials and other source material were identified through electronic searches on MEDLINE (1990–2003, abstract books, and references identified from bibliographies of pertinent articles. Eligible studies were the clinical trials of statins currently under way in which primary or secondary outcomes included the statins’ nonlipid (ie, pleiotropic effect(s. Data were extracted and trial quality was assessed by the authors. Results: Of the 22 ongoing trials of the nonlipid effects of statins identified, 10 assessed inflammatory markers and plaque stabilization, 4 assessed oxidized low density lipoprotein/vascular oxidant stress, 3 assessed end-stage renal disease, 3 assessed fibrinogen/viscosity, 2 assessed endothelial function, 2 assessed acute coronary syndrome, 2 assessed aortic stenosis progression, and 1 each assessed hypertension, osteoporosis, ischemic burden, Alzheimer’s disease, multiple sclerosis, and stroke (outcomes often overlapped. Conclusion: Given the excellent safety and tolerability of statins as a class, full exploration of their pleiotropic effects has the potential to provide additional benefits to many patients

  5. The effect of statins on average survival in randomised trials, an analysis of end point postponement

    DEFF Research Database (Denmark)

    Kristensen, Malene Lopez; Christensen, Palle Mark; Hallas, Jesper

    2015-01-01

    OBJECTIVE: To estimate the average postponement of death in statin trials. SETTING: A systematic literature review of all statin trials that presented all-cause survival curves for treated and untreated. INTERVENTION: Statin treatment compared to placebo. PRIMARY OUTCOME MEASURES: The average...... in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively. CONCLUSIONS: Statin treatment results in a surprisingly small average gain in overall survival within the trials' running time. For patients whose life expectancy...

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

    Directory of Open Access Journals (Sweden)

    Yu Chih-Chieh

    2012-05-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

  8. Statin Therapy and Outcomes in Trials of Nintedanib in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Kreuter, Michael; Costabel, Ulrich; Richeldi, Luca; Cottin, Vincent; Wijsenbeek, Marlies; Bonella, Francesco; Bendstrup, Elisabeth; Maher, Toby M; Wachtlin, Daniel; Stowasser, Susanne; Kolb, Martin

    2018-02-07

    Cardiovascular comorbidities are frequent in patients with idiopathic pulmonary fibrosis (IPF), and many patients with IPF receive treatment with statins to reduce cardiovascular risk. We investigated whether statin use at baseline was associated with differences in disease progression in placebo-treated patients or influenced the treatment effect of nintedanib in the INPULSIS® trials. Post-hoc subgroup analyses of patients receiving versus not receiving statins at baseline using pooled data from the INPULSIS® trials. At baseline, 312 patients received statins and 749 did not. The annual rates of decline in forced vital capacity (FVC) in patients treated with nintedanib and placebo, respectively, were -78.9 and -187.6 mL/year in patients who received statins at baseline, and -127.9 and -237.9 mL/year in patients who did not. The effect of nintedanib was consistent across subgroups (p = 0.9590). In the INPULSIS® trials, there was a numerically lower FVC decline in placebo-treated patients with IPF who received statins at baseline versus those who did not. Use of statins at baseline did not influence the treatment effect of nintedanib. Prospective data are needed to assess the impact of statins on the course of IPF. © 2018 S. Karger AG, Basel.

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

    Science.gov (United States)

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

    2017-11-01

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

  10. From 4S to IDEAL: the health economics of the statin trials.

    Science.gov (United States)

    Lindgren, Peter; Jönsson, Bengt

    2009-04-01

    The introduction of statins led to much interest in their health economic aspects as they were initially perceived as efficacious but potentially expensive. Consequently, abundant literature exists examining the cost effectiveness of various statins, with analyses estimating the costs of preventing a single cardiovascular event using trial-based data, as well as long-term modelling studies using standardized outcomes such as cost per life-years gained or cost per quality-adjusted life-years. Economic evaluations based on clinical trials with hard endpoints indicate that the improved care associated with statin therapy came at a reasonable price in most risk groups. Variations between study results can largely be explained by differences in drug prices and absolute risk in the studied populations. This holds true for both within-trial analyses and modelling studies. The introduction of generic statins has led to sharp price reductions. Consequently, statin use today would be associated with greater cost savings in the indications that were first studied in clinical trials. New therapies entering the field must now compare favourably with statin therapy, whereas earlier a comparison versus placebo would have been sufficient to demonstrate cost effectiveness.

  11. Remote ischemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty (RIC-STEMI): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Gaspar, António; Pereira, Miguel Álvares; Azevedo, Pedro; Lourenço, André; Marques, Jorge; Leite-Moreira, Adelino

    2015-09-08

    ST-elevation myocardial infarction (STEMI) accounts for nearly one third of acute coronary syndromes. Despite improved STEMI patient care, mortality remains high, contributing significantly to the ischemic heart disease burden. This may partly be related to ischemia-reperfusion injury (IRI). Remote ischemic conditioning (RIC), through short cycles of ischemia-reperfusion applied to a limb, has been shown to reduce IRI in various clinical settings. Our primary hypothesis is that RIC will reduce adverse events related to STEMI when applied as adjunctive therapy to primary percutaneous coronary intervention (PCI). "Remote ischemic conditioning in ST-elevation myocardial infarction as adjuvant to primary angioplasty" (RIC-STEMI) is an ongoing prospective, single-center, open-label, randomized controlled trial to assess whether RIC as an adjunctive therapy during primary PCI in patients presenting with STEMI can improve clinical outcomes. After enrollment, participants are randomized according to a computer-generated randomization schedule, in a ratio of 1:1 to RIC or no intervention, in blocks of four individuals. RIC is begun at least 10 min before the estimated time of the first balloon inflation and its duration is 30 min. Ischemia is induced by three cycles of inflation of a blood pressure cuff placed on the left lower limb to 200 mmHg and then deflation to 0 mmHg for another 5 min. Primary endpoint is a combined endpoint of death from cardiac cause or hospitalization for heart failure (HF) on follow-up (including device implantation: implantable cardioverter defibrillator, cardiac resynchronization and left ventricular assist device). Secondary endpoints are myocardial infarction (MI) size (estimated by the 48 h area under the curve of serum troponin I levels), development of Q-wave MI, left ventricular function (assessed by echocardiography within the first 3 days after admission), contrast-induced nephropathy, in-hospital mortality, all-cause mortality and

  12. The effect of statins on average survival in randomised trials, an analysis of end point postponement.

    Science.gov (United States)

    Kristensen, Malene Lopez; Christensen, Palle Mark; Hallas, Jesper

    2015-09-24

    To estimate the average postponement of death in statin trials. A systematic literature review of all statin trials that presented all-cause survival curves for treated and untreated. Statin treatment compared to placebo. The average postponement of death as represented by the area between the survival curves. 6 studies for primary prevention and 5 for secondary prevention with a follow-up between 2.0 and 6.1 years were identified. Death was postponed between -5 and 19 days in primary prevention trials and between -10 and 27 days in secondary prevention trials. The median postponement of death for primary and secondary prevention trials were 3.2 and 4.1 days, respectively. Statin treatment results in a surprisingly small average gain in overall survival within the trials' running time. For patients whose life expectancy is limited or who have adverse effects of treatment, withholding statin therapy should be considered. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  13. Relation of Left Ventricular Mass and Infarct Size in Anterior Wall ST-Segment Elevation Acute Myocardial Infarction (from the EMBRACE STEMI Clinical Trial).

    Science.gov (United States)

    Daaboul, Yazan; Korjian, Serge; Weaver, W Douglas; Kloner, Robert A; Giugliano, Robert P; Carr, Jim; Neal, Brandon J; Chi, Gerald; Cochet, Madeleine; Goodell, Laura; Michalak, Nathan; Rusowicz-Orazem, Luke; Alkathery, Turky; Allaham, Haytham; Routray, Sujit; Szlosek, Donald; Jain, Purva; Gibson, C Michael

    2016-09-01

    Biomarker measures of infarct size and myocardial salvage index (MSI) are important surrogate measures of clinical outcomes after a myocardial infarction. However, there is variability in infarct size unaccounted for by conventional adjustment factors. This post hoc analysis of Evaluation of Myocardial Effects of Bendavia for Reducing Reperfusion Injury in Patients With Acute Coronary Events (EMBRACE) ST-Segment Elevation Myocardial Infarction (STEMI) trial evaluates the association between left ventricular (LV) mass and infarct size as assessed by areas under the curve for creatine kinase-MB (CK-MB) and troponin I release over the first 72 hours (CK-MB area under the curve [AUC] and troponin I [TnI] AUC) and the MSI. Patients with first anterior STEMI, occluded left anterior descending artery, and available LV mass measurement in EMBRACE STEMI trial were included (n = 100) (ClinicalTrials.govNCT01572909). MSI, end-diastolic LV mass on day 4 cardiac magnetic resonance, and CK-MB and troponin I concentrations were evaluated by a core laboratory. After saturated multivariate analysis, dominance analysis was performed to estimate the contribution of each independent variable to the predicted variance of each outcome. In multivariate models that included age, gender, body surface area, lesion location, smoking, and ischemia time, LV mass remained independently associated with biomarker measures of infarct size (CK-MB AUC p = 0.02, TnI AUC p = 0.03) and MSI (p = 0.003). Dominance analysis demonstrated that LV mass accounted for 58%, 47%, and 60% of the predicted variances for CK-MB AUC, TnI AUC, and MSI, respectively. In conclusion, LV mass accounts for approximately half of the predicted variance in biomarker measures of infarct size. It should be considered as an adjustment variable in studies evaluating infarct size. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Statins and bone health in postmenopausal women: a systematic review of randomized controlled trials.

    Science.gov (United States)

    Yue, Jirong; Zhang, Xuemei; Dong, Birong; Yang, Ming

    2010-01-01

    Basic science data, animal studies, and observational human studies suggest that the lipid-lowering cardiovascular family of statin medications might decrease fractures, increase bone density, and have a positive effect on bone turnover markers. The primary purpose of our review was to determine whether statins can prevent fractures in postmenopausal women; as secondary and explanatory factors, bone density and bone biomarker data were also evaluated. All randomized controlled trials assessing the effect of statins on bone mineral density were included; bone turnover markers and fractures in postmenopausal women were considered. We identified six randomized trials involving 3,022 participants. Statins had no association with decreasing incidence of fracture. There was no statistical difference in the reduction in lumbar spine or total hip bone density. Other predictors of osteoporosis-related fracture risk, including markers relating to bone resorption (c-telopeptide of type I collagen and n-telopeptide of type I collagen) and bone formation (osteocalcin and bone-specific alkaline phosphates), did not show any significant changes. The trials included in our review, which included data on 3,022 women (mean age, >62.7 y), do not indicate that statin use prevents fractures or increases bone density.

  15. Utility of post-procedural anticoagulation after primary PCI for STEMI: insights from a pooled analysis of the HORIZONS-AMI and EUROMAX trials.

    Science.gov (United States)

    Ducrocq, Gregory; Steg, Philippe Gabriel; Van't Hof, Arnoud; Zeymer, Uwe; Mehran, Roxana; Hamm, Christian W; Bernstein, Debra; Prats, Jayne; Deliargyris, Efthymios N; Stone, Gregg W

    2017-10-01

    Many sites routinely continue anticoagulation after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction (STEMI), despite an unclear benefit-risk ratio. We evaluated the impact of this strategy on 30-day outcomes from a pooled patient-level database of two large primary percutaneous coronary intervention trials. EUROMAX and HORIZONS-AMI were both multicentre, international randomised trials comparing bivalirudin to heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary percutaneous coronary intervention. Outcomes at 30 days were analysed according to the use of post-procedural anticoagulation (unfractionated or low-molecular-weight heparins or fondaparinux) outside of the catheterisation laboratory. Among 5239 patients undergoing primary percutaneous coronary intervention, 2153 (41.1%) received post-procedural anticoagulation. After adjusting for differences in baseline variables, there were no differences in the 30-day rates of adverse ischaemic events between patients without versus with post-procedural anticoagulation: adjusted odds ratio for major adverse cardiac events 0.80; 95% confidence interval 0.60-1.07; P=0.14; adjusted odds ratio for stent thrombosis 0.82; 95% confidence interval 0.55-1.24; P=0.35; adjusted odds ratio for death 1.07; 95% confidence interval 0.69-1.66; P=0.77. Conversely, protocol-defined major bleeding was decreased without post-procedural anticoagulation: adjusted odds ratio 0.74; 95% confidence interval 0.58-0.94; P=0.01. Similar results were observed for Thrombolysis In Myocardial Infarction major and minor bleeding. In this large STEMI database, a substantial proportion of primary percutaneous coronary intervention patients received post-procedural anticoagulation, which in turn was associated with higher bleeding rates without any reduction in ischaemic events. Therefore, routine post-procedural anticoagulation after primary percutaneous

  16. Statins: Cost analysis in Indian scenario from eight major clinical trials

    Directory of Open Access Journals (Sweden)

    Sanmukhani J

    2010-01-01

    Full Text Available Background and Aims: Coronary heart disease (CHD is the leading cause of death in India resulting in loss of young Indians. Statins have proved to reduce the CHD mortality in various clinical trials. The aim of the study is to find the cost-effectiveness ratio (CER for each major coronary event averted and a coronary death avoided by use of statins in different clinical settings based on the data from the major clinical trials on statins. Materials and Methods: Using electronic database and as per our inclusion and exclusion criteria we selected the West of Scotland Coronary Prevention Study (WOSCOPS, the Air Force Coronary Atherosclerosis Prevention Study (AFCAPS and the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA study for primary prevention; the Cholesterol and Recurrent Events Trial (CARE, the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID Study and the Scandinavian Simvastatin Survival Study (4S for secondary prevention and two studies, the Heart Protection Study (HPS and the Pravastatin in elderly individuals at risk of vascular disease (PROSPER study for high-risk patients. The results of these studies were used for cost-effectiveness analysis of statins in different patient groups. Statistical Analysis: Absolute risk reduction, Number Needed to Benefit (NNTB, NNTB/year for total sample and in subgroups of males, females and age >65 was derived. CER for branded and generic versions was calculated by using the prices of statins listed in Indian Drug Review Triple i. Results: Cost-effectiveness ratio (CER in primary prevention studies i.e., the WOSCOPS, the AFCAPS and the ASCOT-LLA was Rs. 25.8 lacs, Rs. 23.8 lacs and Rs. 7.9 lacs per major coronary event averted respectively. CER in secondary prevention studies i.e., the CARE and the LIPID was approximately Rs. 20 lacs per major coronary event averted while it was Rs. 52.4 lacs and Rs. 37 lacs per coronary heart disease (CHD death avoided

  17. Statins in hypercholesterolaemia: A dose-specific meta-analysis of lipid changes in randomised, double blind trials

    Directory of Open Access Journals (Sweden)

    Moore R Andrew

    2003-12-01

    Full Text Available Abstract Background Statins alter lipid concentrations. This systematic review determined the efficacy of particular statins, in terms of their ability to alter cholesterol. Review methods PubMed, the Cochrane Library, references lists of reports, and reviews were searched (September 2001 for randomised, double blind trials of statins for cholesterol in trials of 12 weeks or longer. Mean change in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides was calculated using pooled data for particular statins, and for particular doses of a statin. Pre-planned sensitivity analyses were used to determine the effects of initial concentration of total cholesterol, study duration, the effects of major trials, and effects in placebo versus active controlled trials. Information was not collected on adverse events. Results Different statins at a range of doses reduced total cholesterol by 17–35% and LDL-cholesterol by 24–49% from baseline. Lower doses of statins generally produced less cholesterol lowering, though for most statins in trials of 12 weeks or longer there was at best only a weak relationship between dose and cholesterol reduction. Duration of treatment and baseline total cholesterol concentration did not alter the amount of the benefit attained. Conclusions Statins are effective medicines and confer benefit to patients in terms of primary and secondary prevention of coronary heart disease. Reductions in total cholesterol of 25% or more and LDL cholesterol of more than 30% were recorded for fixed doses of simvastatin 40 mg, atorvastatin 10 mg, and rosuvastatin 5 mg and 10 mg.

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

    Science.gov (United States)

    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.

  19. Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial.

    Science.gov (United States)

    Bjarnadottir, Olöf; Romero, Quinci; Bendahl, Pär-Ola; Jirström, Karin; Rydén, Lisa; Loman, Niklas; Uhlén, Mathias; Johannesson, Henrik; Rose, Carsten; Grabau, Dorthe; Borgquist, Signe

    2013-04-01

    Lipophilic statins purportedly exert anti-tumoral effects on breast cancer by decreasing proliferation and increasing apoptosis. HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway, is the target of statins. However, data on statin-induced effects on HMGCR activity in cancer are limited. Thus, this pre-operative study investigated statin-induced effects on tumor proliferation and HMGCR expression while analyzing HMGCR as a predictive marker for statin response in breast cancer treatment. The study was designed as a window-of-opportunity trial and included 50 patients with primary invasive breast cancer. High-dose atorvastatin (i.e., 80 mg/day) was prescribed to patients for 2 weeks before surgery. Pre- and post-statin paired tumor samples were analyzed for Ki67 and HMGCR immunohistochemical expression. Changes in the Ki67 expression and HMGCR activity following statin treatment were the primary and secondary endpoints, respectively. Up-regulation of HMGCR following atorvastatin treatment was observed in 68 % of the paired samples with evaluable HMGCR expression (P = 0.0005). The average relative decrease in Ki67 expression following atorvastatin treatment was 7.6 % (P = 0.39) in all paired samples, whereas the corresponding decrease in Ki67 expression in tumors expressing HMGCR in the pre-treatment sample was 24 % (P = 0.02). Furthermore, post-treatment Ki67 expression was inversely correlated to post-treatment HMGCR expression (rs = -0.42; P = 0.03). Findings from this study suggest that HMGCR is targeted by statins in breast cancer cells in vivo, and that statins may have an anti-proliferative effect in HMGCR-positive tumors. Future studies are needed to evaluate HMGCR as a predictive marker for the selection of breast cancer patients who may benefit from statin treatment.

  20. Effect of statin therapy on paraoxonase-1 status: A systematic review and meta-analysis of 25 clinical trials.

    Science.gov (United States)

    Ferretti, Gianna; Bacchetti, Tiziana; Sahebkar, Amirhossein

    2015-10-01

    Decreased activity of the enzyme paraoxonase-1 (PON1) has been demonstrated in cardiovascular diseases. Statins, the forefront of pharmacotherapy for dyslipidemia, have been shown to enhance PON1 activity but clinical findings have not been conclusive. To systematically review the clinical findings on the impact of statin therapy on PON1 status (protein concentrations and activities of paraoxonase and arylesterase) and calculate an effect size for the mentioned effects through meta-analysis of available data. Scopus and Medline databases were searched to identify clinical trials. A random-effects model and the generic inverse variance method were used for quantitative data synthesis. Sensitivity analysis was conducted using the one-study remove approach. Random-effects meta-regression was performed to assess the impact of potential confounders on the estimated effect sizes. Meta-analysis suggested that statin therapy is associated with a significant elevation of PON1 paraoxonase and arylesterase activities, but not PON1 protein concentration. The PON1-enhancing effects of statins were robust in the sensitivity analyses and were independent of statin dose, treatment duration and changes in plasma low-density lipoprotein cholesterol concentration. The increase of paraoxonase and arylesterase activities with statins is a pleiotropic lipid-independent clinical benefit that may partly explain the putative effects of statins in preventing cardiovascular outcomes. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Industry sponsorship bias in research findings: a network meta-analysis of LDL cholesterol reduction in randomised trials of statins

    Science.gov (United States)

    Dias, Sofia; Ades, A E

    2014-01-01

    Objective To explore the risk of industry sponsorship bias in a systematically identified set of placebo controlled and active comparator trials of statins. Design Systematic review and network meta-analysis. Eligibility Open label and double blind randomised controlled trials comparing one statin with another at any dose or with control (placebo, diet, or usual care) for adults with, or at risk of developing, cardiovascular disease. Only trials that lasted longer than four weeks with more than 50 participants per trial arm were included. Two investigators assessed study eligibility. Data sources Bibliographic databases and reference lists of relevant articles published between 1 January 1985 and 10 March 2013. Data extraction One investigator extracted data and another confirmed accuracy. Main outcome measure Mean absolute change from baseline concentration of low density lipoprotein (LDL) cholesterol. Data synthesis Study level outcomes from randomised trials were combined using random effects network meta-analyses. Results We included 183 randomised controlled trials of statins, 103 of which were two-armed or multi-armed active comparator trials. When all of the existing randomised evidence was synthesised in network meta-analyses, there were clear differences in the LDL cholesterol lowering effects of individual statins at different doses. In general, higher doses resulted in higher reductions in baseline LDL cholesterol levels. Of a total of 146 industry sponsored trials, 64 were placebo controlled (43.8%). The corresponding number for the non-industry sponsored trials was 16 (43.2%). Of the 35 unique comparisons available in 37 non-industry sponsored trials, 31 were also available in industry sponsored trials. There were no systematic differences in magnitude between the LDL cholesterol lowering effects of individual statins observed in industry sponsored versus non-industry sponsored trials. In industry sponsored trials, the mean change from baseline LDL

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

    Science.gov (United States)

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

    2010-01-01

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

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

    LENUS (Irish Health Repository)

    2013-01-03

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

  4. Pooled analysis of two randomized trials comparing titanium-nitride-oxide-coated stent versus drug-eluting stent in STEMI.

    Science.gov (United States)

    Tuomainen, Petri O; Sia, Jussi; Nammas, Wail; Niemelä, Matti; Airaksinen, Juhani K E; Biancari, Fausto; Karjalainen, Pasi P

    2014-07-01

    We performed a pooled analysis based on patient-level data from the TITAX-AMI and BASE-ACS trials to evaluate the outcome of titanium-nitride-oxide-coated bioactive stents vs drug-eluting stents in patients with ST-segment elevation myocardial infarction at 2-year follow-up. The TITAX-AMI trial compared bioactive stents with paclitaxel-eluting stents in 425 patients with acute myocardial infarction. The BASE-ACS trial compared bioactive stents with everolimus-eluting stents in 827 patients with acute coronary syndrome. The primary endpoint for the pooled analysis was major adverse cardiac events: a composite of cardiac death, recurrent myocardial infarction, or ischemia-driven target lesion revascularization at 2-year follow-up. The pooled analysis included 501 patients; 245 received bioactive stents, and 256 received drug-eluting stents. The pooled bioactive stent group was associated with a risk ratio of 0.85 for major adverse cardiac events (95% confidence interval, 0.53-1.35; P=.49) compared to the pooled drug-eluting stent group. Similarly, the pooled bioactive stent group was associated with a risk ratio of 0.71 for cardiac death (95% confidence interval, 0.26-1.95; P=.51), 0.44 for recurrent myocardial infarction (95% confidence interval, 0.20-0.97; P=.04), and 1.39 for ischemia-driven target lesion revascularization (95% confidence interval, 0.74-2.59; P=.30), compared to the pooled drug-eluting stent group. These results were confirmed by propensity-score adjusted analysis of the combined datasets. In patients with ST-segment elevation myocardial infarction, bioactive stents were associated with lower rates of recurrent myocardial infarction compared to drug-eluting stents at 2-year follow-up; yet, the rates of cardiac death and ischemia-driven target lesion revascularization were similar. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

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

    Science.gov (United States)

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

    2015-12-01

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

  6. Statins: Mechanisms of neuroprotection

    NARCIS (Netherlands)

    van der Most, Peter J.; Dolga, Amalia; Nijholt, Ingrid M.; Luiten, Paul G. M.; Eisel, Ulrich L. M.

    Clinical trials report that the class of drugs known as statins may be neuroprotective in Alzheimer's and Parkinson's disease, and further trials are currently underway to test whether these drugs are also beneficial in multiple sclerosis and acute stroke treatment. Since statins are well tolerated

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

    Science.gov (United States)

    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.

  8. Rationale and design of the Statins Evaluation in Coronary procedUres and REvascularization: The SECURE-PCI Trial.

    Science.gov (United States)

    Berwanger, Otavio; de Barros E Silva, Pedro G M; Dall Orto, Frederico Toledo Campo; de Andrade, Pedro Beraldo; de Castro Bienert, Igor Ribeiro; Bosso, Carlos Eduardo; Mangione, José; Polanczyk, Carisi Anne; Sousa, Amanda; Kalil, Renato; de Moura Santos, Luciano; Sposito, Andrei C; Rech, Rafael L; Sousa, Antonio Carlos Sobral; Baldissera, Felipe; Nascimento, Bruno Ramos; de Andrade Jesuíno, Isabella; Santucci, Eliana Vieira; Damiani, Lucas Petri; Laranjeira, Ligia N; Borges de Oliveira, Juliana A; Giraldez, Roberto R; Cavalcanti, Alexandre Biasi; Pereira, Sabrina Bernardez; Mattos, Luiz Alberto; Armaganijan, Luciana Vidal; Guimarães, Hélio Penna; Sousa, José Eduardo; Alexander, John H; Granger, Christopher B; Lopes, Renato D

    2018-04-01

    Previous evidence suggests that acute treatment with statins reduce atherosclerotic complications, including periprocedural myocardial infarction, but currently, there are no large, adequately powered studies to define the effects of early, high-dose statins in patients with acute coronary syndrome (ACS) and planned invasive management. The main goal of Statins Evaluation in Coronary procedUres and REvascularization (SECURE-PCI) Trial is to determine whether the early use of a loading dose of 80 mg of atorvastatin before an intended percutaneous coronary intervention followed by an additional dose of 80 mg 24 hours after the procedure will be able to reduce the rates of major cardiovascular events at 30 days in patients with an ACS. The SECURE-PCI study is a pragmatic, multicenter, double-blind, placebo-controlled randomized trial planned to enroll around 4,200 patients in 58 different sites in Brazil. The primary outcome is the rate of major cardiovascular events at 30 days defined as a composite of all-cause mortality, nonfatal acute myocardial infarction, nonfatal stroke, and coronary revascularization. The SECURE PCI is a large randomized trial testing a strategy of early, high-dose statin in patients with ACS and will provide important information about the acute treatment of this patient population. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Comparison of PCSK9 Inhibitor Evolocumab vs Ezetimibe in Statin-Intolerant Patients: Design of the Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 3 (GAUSS-3) Trial.

    Science.gov (United States)

    Nissen, Steven E; Dent-Acosta, Ricardo E; Rosenson, Robert S; Stroes, Erik; Sattar, Naveed; Preiss, David; Mancini, G B John; Ballantyne, Christie M; Catapano, Alberico; Gouni-Berthold, Ioanna; Stein, Evan A; Xue, Allen; Wasserman, Scott M; Scott, Rob; Thompson, Paul D

    2016-03-01

    Statins are the accepted standard for lowering low-density lipoprotein cholesterol (LDL-C). However, 5% to 10% of statin-treated patients report intolerance, mostly due to muscle-related adverse effects. Challenges exist to objective identification of statin-intolerant patients. Evolocumab is a monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9), resulting in marked LDL-C reduction. We report the design of Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin-Intolerant Subjects 3 (GAUSS-3), a phase 3, multicenter, randomized, double-blind, ezetimibe-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 kinase elevation accompanied by muscle symptoms while on 1 statin. This trial has 2 co-primary endpoints: mean percent change from baseline in LDL-C at weeks 22 and 24 and percent change from baseline in LDL-C at week 24. Key secondary efficacy endpoints include change from baseline in LDL-C, percent of patients attaining LDL-C <70 mg/dL (1.81 mmol/L), and percent change from baseline in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. Recruitment of 511 patients was completed on November 28, 2014. © 2016 Wiley Periodicals, Inc.

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

    NARCIS (Netherlands)

    Moriarty, Patrick M.; Thompson, Paul D.; Cannon, Christopher P.; Guyton, John R.; Bergeron, Jean; Zieve, Franklin J.; Bruckert, Eric; Jacobson, Terry A.; Kopecky, Stephen L.; Baccara-Dinet, Marie T.; Du, Yunling; Pordy, Robert; Gipe, Daniel A.; Drexel, Heinz; Kaser, Susanne; Toplak, Hermann; Baass, Alexis; Gaudet, Daniel; Farnier, Michel; Krempf, Michel; Moulin, Philippe; Serusclat, Pierre; Cohen, Hofit; Gavish, Dov; Hussein, Osama; Maislos, Maximo; Schurr, Daniel; Arca, Marcello; Averna, Maurizio; Pozzi, Claudio; Balsamo, Cinisello; Heggen, Eli; Langslet, Gisle; Al-Bahrani, Ali; Blagden, Mark; O'Kane, Maurice; Reynolds, Tim; Viljoen, Adie; Andersen, James; Awasty, Vivek; Bayron, Carlos; Bestermann, William; Bolster, Eric; deGoma, Emil; Dunn, Fredrick; Duprez, Daniel; Elam, Marshall; El Shahawy, Mahfouz; Faillace, Robert; Freeman, Mason; Goyal, Neil; Guyton, John; Hemphill, Linda; Huffman, Cynthia; Jain, Vandana; Kopecky, Stephen; Koren, Michael; Lepor, Norman; Lesko, Michael; Linton, MacRae; Loh, Irving; Malik, Amir; Mascarenhas, Vernon; Moriarty, Patrick; Mulford, Mim; Muse, Derek; O'dea, Daniel; Shaoulian, Emanuel; Smith, Donald; Stearns, Pamela; Thompson, Paul; Toth, Phillip; Turner, Traci; Vardi, Gil; Voyce, Stephen; Weinstein, Debra; Weiss, Robert; Zieve, Franklin; Ginsberg, Henry; Robinson, Jennifer G.; Rader, Daniel J.; Colhoun, Helen M.; Kastelein, John J. P.; Olsson, Anders; Waters, David; Larrey, Dominique; Rosenson, Robert S.; Patriarca, Peter A.; Molenberghs, Geert; Tricoci, Pierluigi; Mahaffey, Kenneth W.; Lopes, Renato D.; Shah, Bimal R.; Mehta, Rajendra H.; Roe, Matthew T.; Eapen, Zubin; Armaganijan, Luciana; Bertolami, Adriana; Leonardi, Sergio; Kolls, Bradley J.; Jordan, J. Dedrick; Ducrocq, Grégory; Puymirat, Etienne; Mathews, Robin; Alexander, Karen; Melloni, Chiara

    2015-01-01

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

  11. Role of statins in preventing cardiac surgery-associated acute kidney injury: an updated meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    He S

    2018-03-01

    Full Text Available Song-jian He, Qiang Liu, Hua-qiu Li, Fang Tian, Shi-yu Chen, Jian-xin Weng Department of Cardiology, Shenzhen Sun Yat-sen Cardiovascular Hospital, Shenzhen, China Background: The prevention of cardiac surgery-associated acute kidney injury (CSA-AKI by statins remains controversial. Therefore, the present meta-analysis including randomized controlled trials (RCTs was performed to assess the effect of perioperative statin on CSA-AKI. Methods: Two reviewers independently searched for RCTs about perioperative statin for prevention of CSA-AKI. The primary endpoint was CSA-AKI. Relative risk was calculated between statin and placebo for preventing CSA-AKI using the random-effect model or fixed-effect model according to different heterogeneity. Results: Eight RCTs met inclusion criteria, including five studies with atorvastatin, two with rosuvastatin, and one with simvastatin. There were 1,603 patients receiving statin treatment and 1,601 with placebo. Perioperative statin therapy did not reduce the incidence of CSA-AKI (relative risk =1.17, 95% CI: 0.98–1.39, p=0.076. Furthermore, perioperative statin increased the risk of CSA-AKI in the subgroup analysis with clear definition of CSA-AKI and those with JADAD score >3. Perioperative rosuvastatin produced slightly significantly higher risk of AKI than atorvastatin therapy (p=0.070. Statin intervention both pre and post surgery slightly increased the risk of CSA-AKI versus preoperative statin therapy alone (p=0.040. Conclusions: Perioperative statin therapy might increase the risk of CSA-AKI after cardiac surgery. Keywords: statin, perioperative, acute kidney injury, cardiac surgery, meta-analysis

  12. Response to Statin Therapy in Obstructive Sleep Apnea Syndrome: A Multicenter Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Marie Joyeux-Faure

    2014-01-01

    Full Text Available Rationale. Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA. Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. Methods. This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint measured by peripheral arterial tone (PAT. Secondary endpoints included office blood pressure (BP, early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV, and metabolic parameters. Results. 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m2. In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (−0.29; 0.28, P=0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: −6.34 mmHg (−12.68; −0.01, P=0.050 whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. Conclusion. In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.

  13. Statins and breast cancer prognosis

    DEFF Research Database (Denmark)

    Ahern, T. P.; Lash, T. L.; Damkier, P.

    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...

  14. Primary Prevention With Statins

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Yongchuan Li

    Full Text Available A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathy have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of short-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of the potential benefits of statin therapy.We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statin treatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2-5 days after contrast administration and need for dialysis.Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall results based on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significant reduction in risk of CIN (RR =0.51, 95% CI 0.34-0.76, p =0.001; I(2 = 0%. The incidence of acute renal failure requiring dialysis was not significant different after the use of statin (RR = 0.33, 95% CI 0.05-2.10, p = 0.24; I(2 = 0%. The use of statin was not associated with a significant decrease in the plasma C-reactive protein level (SMD -0.64, 95% CI: -1.57 to 0.29, P = 0.18, I(2 = 97%.Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered in the context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statin based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for statin in CIN prevention.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    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...... strokes in subjects with recent stroke or transient ischemic attack (n=4731). We analyzed SPARCL trial data to determine whether treatment favorably shifts the distribution of severities of ischemic cerebrovascular outcomes. METHODS: Severity was assessed with the National Institutes of Health Stroke...... Scale, Barthel Index, and modified Rankin Scale score at enrollment (1 to 6 months after the index event) and 90 days poststroke in subjects having a stroke during the trial. RESULTS: Over 4.9 years, strokes occurred in 576 subjects. There were reductions in fatal, severe (modified Rankin Scale score 5...

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Statin-Associated Side Effects.

    Science.gov (United States)

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

    2016-05-24

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

  20. 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.

    Science.gov (United States)

    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

  1. STEMI time delays: A clinical perspective

    NARCIS (Netherlands)

    M.J. de Boer (Menko Jan); F. Zijlstra (Felix)

    2015-01-01

    textabstractSTEMI time delays have been introduced as a performance indicator or marker of quality of care. As they are only one part of a very complex medical process, one should be aware of concomitant issues that may be overlooked or even be more important with regard to clinical outcome of STEMI

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  4. Current Evidence to Justify, and the Methodological Considerations for a Randomised Controlled Trial Testing the Hypothesis that Statins Prevent the Malignant Progression of Barrett's Oesophagus

    Directory of Open Access Journals (Sweden)

    David Thurtle

    2014-12-01

    Full Text Available Barrett’s oesophagus is the predominant risk factor for oesophageal adenocarcinoma, a cancer whose incidence is increasing and which has a poor prognosis. This article reviews the latest experimental and epidemiological evidence justifying the development of a randomised controlled trial investigating the hypothesis that statins prevent the malignant progression of Barrett’s oesophagus, and explores the methodological considerations for such a trial. The experimental evidence suggests anti-carcinogenic properties of statins on oesophageal cancer cell lines, based on the inhibition of the mevalonate pathway and the production of pro-apoptotic proteins. The epidemiological evidence reports inverse associations between statin use and the incidence of oesophageal carcinoma in both general population and Barrett’s oesophagus cohorts. Such a randomised controlled trial would be a large multi-centre trial, probably investigating simvastatin, given the wide clinical experience with this drug, relatively low side-effect profile and low financial cost. As with any clinical trial, high adherence is important, which could be increased with therapy, patient, doctor and system-focussed interventions. We would suggest there is now sufficient evidence to justify a full clinical trial that attempts to prevent this aggressive cancer in a high-risk population.

  5. Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial.

    Science.gov (United States)

    Alfaddagh, Abdulhamied; Elajami, Tarec K; Ashfaque, Hasan; Saleh, Mohamad; Bistrian, Bruce R; Welty, Francine K

    2017-12-15

    -intensity statin, suggests that statin intensity affects plaque volume. URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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

    Science.gov (United States)

    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.

  7. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab.

    Science.gov (United States)

    Stroes, Erik; Colquhoun, David; Sullivan, David; Civeira, Fernando; Rosenson, Robert S; Watts, Gerald F; Bruckert, Eric; Cho, Leslie; Dent, Ricardo; Knusel, Beat; Xue, Allen; Scott, Rob; Wasserman, Scott M; Rocco, Michael

    2014-06-17

    This study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin doses. Statin intolerance, which is predominantly due to muscle-related side effects, is reported in up to 10% to 20% of patients. Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients. The GAUSS-2 (Goal Achievement after Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects) trial was a 12-week, double-blind study of randomized patients (2:2:1:1) to evolocumab 140 mg every two weeks (Q2W) or evolocumab 420 mg once monthly (QM) both with daily oral placebo or subcutaneous placebo Q2W or QM both with daily oral ezetimibe 10 mg. Co-primary endpoints were percent change from baseline in LDL-C at the mean of weeks 10 and 12, and at week 12. Three hundred seven patients (age 62 ± 10 years; LDL-C 193 ± 59 mg/dl) were randomized. Evolocumab reduced LDL-C from baseline by 53% to 56%, corresponding to treatment differences versus ezetimibe of 37% to 39% (p <0.001). Muscle adverse events occurred in 12% of evolocumab-treated patients and 23% of ezetimibe-treated patients. Treatment-emergent adverse events and laboratory abnormalities were comparable across treatment groups. Robust efficacy combined with favorable tolerability makes evolocumab a promising therapy for addressing the largely unmet clinical need in high-risk patients with elevated cholesterol who are statin intolerant. (Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects-2; NCT01763905). Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Delayed educational reminders for long-term medication adherence in ST-elevation myocardial infarction (DERLA-STEMI: Protocol for a pragmatic, cluster-randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ivers Noah M

    2012-06-01

    Full Text Available Abstract Background Despite evidence-based recommendations supporting long-term use of cardiac medications in patients post ST-elevation myocardial infarction, adherence is known to decline over time. Discontinuation of cardiac medications in such patients is associated with increased mortality. Methods/design This is a pragmatic, cluster-randomized controlled trial with blinded outcome assessment and embedded qualitative process evaluation. Patients from one health region in Ontario, Canada who undergo a coronary angiogram during their admission for ST-elevation myocardial infarction and who survive their initial hospitalization will be included. Allocation of eligible patients to intervention or usual care will take place within one week after the angiogram using a computer-generated random sequence. To avoid treatment contamination, patients treated by the same family physician will be allocated to the same study arm. The intervention consists of recurrent, personalized, paper-based educational messages and reminders sent via post on behalf of the interventional cardiologist to the patient, family physician, and pharmacist urging long-term adherence to secondary prevention medications. The primary outcome is the proportion of patients who report in a phone interview taking all relevant classes of cardiac medications at twelve months. Secondary outcomes to be measured at three and twelve months include proportions of patients who report: actively taking each cardiac medication class of interest (item-by-item; stopping medications due to side effects; taking one or two or three medication classes concurrently; a perfect Morisky Medication Adherence Score for cardiac medication compliance; and having a discussion with their family physician about long-term adherence to cardiac medications. Self-reported measures of adherence will be validated using administrative data for prescriptions filled. Discussion This intervention is designed to be

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

    DEFF Research Database (Denmark)

    Räber, Lorenz; Taniwaki, Masanori; Zaugg, Serge

    2015-01-01

    AIM: The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition, and phen......AIM: The effect of long-term high-intensity statin therapy on coronary atherosclerosis among patients with acute ST-segment elevation myocardial infarction (STEMI) is unknown. The aim of this study was to quantify the impact of high-intensity statin therapy on plaque burden, composition......, P = 0.15). CONCLUSION: High-intensity rosuvastatin therapy over 13 months is associated with regression of coronary atherosclerosis in non-infarct-related arteries without changes in RF-IVUS defined necrotic core or plaque phenotype among STEMI patients....

  10. A network meta-analysis on randomized trials focusing on the preventive effect of statins on contrast-induced nephropathy

    DEFF Research Database (Denmark)

    Peruzzi, Mariangela; De Luca, Leonardo; Thomsen, Henrik S

    2014-01-01

    Contrast-induced nephropathy is a common complication of iodinated contrast administration. Statins may reduce the risk of contrast-induced nephropathy, but data remain inconclusive. We summarized the evidence based on statins for the prevention of contrast-induced nephropathy with a network meta...

  11. A cluster randomised controlled trial of a pharmacist-led collaborative intervention to improve statin prescribing and attainment of cholesterol targets in primary care.

    Directory of Open Access Journals (Sweden)

    Richard Lowrie

    Full Text Available Small trials with short term follow up suggest pharmacists' interventions targeted at healthcare professionals can improve prescribing. In comparison with clinical guidance, contemporary statin prescribing is sub-optimal and achievement of cholesterol targets falls short of accepted standards, for patients with atherosclerotic vascular disease who are at highest absolute risk and who stand to obtain greatest benefit. We hypothesised that a pharmacist-led complex intervention delivered to doctors and nurses in primary care, would improve statin prescribing and achievement of cholesterol targets for incident and prevalent patients with vascular disease, beyond one year.We allocated general practices to a 12-month Statin Outreach Support (SOS intervention or usual care. SOS was delivered by one of 11 pharmacists who had received additional training. SOS comprised academic detailing and practical support to identify patients with vascular disease who were not prescribed a statin at optimal dose or did not have cholesterol at target, followed by individualised recommendations for changes to management. The primary outcome was the proportion of patients achieving cholesterol targets. Secondary outcomes were: the proportion of patients prescribed simvastatin 40 mg with target cholesterol achieved; cholesterol levels; prescribing of simvastatin 40 mg; prescribing of any statin and the proportion of patients with cholesterol tested. Outcomes were assessed after an average of 1.7 years (range 1.4-2.2 years, and practice level simvastatin 40 mg prescribing was assessed after 10 years.We randomised 31 practices (72 General Practitioners (GPs, 40 nurses. Prior to randomisation a subset of eligible patients were identified to characterise practices; 40% had cholesterol levels below the target threshold. Improvements in data collection procedures allowed identification of all eligible patients (n = 7586 at follow up. Patients in practices allocated to SOS were

  12. 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

    Science.gov (United States)

    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

  13. Statins-More Than Just Plaque Stabilisation

    Directory of Open Access Journals (Sweden)

    Ashish K Khanna

    2008-01-01

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

  14. Statins in acute coronary syndromes.

    Science.gov (United States)

    Sposito, Alexandre Russo; Aguiar Filho, Gentil Barreira de; Aarão, Amanda Rezende; Sousa, Francisco Thiago Tomaz de; Bertolami, Marcelo Chiara

    2011-10-01

    Statins are the main resource available to reduce LDL-cholesterol levels. Their continuous use decreases cardiovascular morbidity and mortality due to atherosclerosis. The administration of these medications demonstrated to be effective in primary and secondary prevention clinical trials in low and high risk patients. Specialists believe that a possible benefit of hypolipidemic therapy in preventing complications of atherosclerotic diseases is in the reduction of deposition of atherogenic lipoproteins in vulnerable areas of the vasculature. Experimental studies with statins have shown an enormous variety of other effects that could extend the clinical benefit beyond the lipid profile modification itself. Statin-based therapies benefit other important components of the atherothrombotic process: inflammation, oxidation, coagulation, fibrinolysis, endothelial function, vasoreactivity and platelet function. The demonstration of the effects that do not depend on cholesterol lowering or the pleiotropic effects of statins provides the theoretical basis for their potential role as adjunctive therapy in acute coronary syndromes. Retrospective analyses of a variety of studies indicate the potential benefit of statins during acute coronary events. Recent clinical studies have addressed this important issue in prospective controlled trials showing strong evidence for the administration of statins as adjunctive therapy in acute coronary syndromes.

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

    Science.gov (United States)

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

    2016-10-01

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

  16. Statin treatment in multiple sclerosis

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease that leads to progressive disability. Statins [hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors] are widely prescribed drugs in hypercholesterolemia. They exert immunomodulatory and neurotrophic effects and are attractive...... of relapse activity, magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS) progression, and adverse events using a fixed-effects model due to low heterogeneity between studies. RESULTS: Eight trials were included in the review [five of statin add-on to interferon (IFN......, proportion of patients with relapse, and whole brain atrophy but not for EDSS progression. In SPMS, statin monotherapy showed significant reduction in brain atrophy and disability progression but no effect on relapse rate. In CIS, a phase II trial showed no difference in relapse activity, MRI activity...

  17. Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin).

    Science.gov (United States)

    Khera, Amit V; Demler, Olga V; Adelman, Steven J; Collins, Heidi L; Glynn, Robert J; Ridker, Paul M; Rader, Daniel J; Mora, Samia

    2017-06-20

    Recent failures of drugs that raised high-density lipoprotein (HDL) cholesterol levels to reduce cardiovascular events in clinical trials have led to increased interest in alternative indices of HDL quality, such as cholesterol efflux capacity, and HDL quantity, such as HDL particle number. However, no studies have directly compared these metrics in a contemporary population that includes potent statin therapy and low low-density lipoprotein cholesterol. HDL cholesterol levels, apolipoprotein A-I, cholesterol efflux capacity, and HDL particle number were assessed at baseline and 12 months in a nested case-control study of the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), a randomized primary prevention trial that compared rosuvastatin treatment to placebo in individuals with normal low-density lipoprotein cholesterol but increased C-reactive protein levels. In total, 314 cases of incident cardiovascular disease (CVD) (myocardial infarction, unstable angina, arterial revascularization, stroke, or cardiovascular death) were compared to age- and gender-matched controls. Conditional logistic regression models adjusting for risk factors evaluated associations between HDL-related biomarkers and incident CVD. Cholesterol efflux capacity was moderately correlated with HDL cholesterol, apolipoprotein A-I, and HDL particle number (Spearman r = 0.39, 0.48, and 0.39 respectively; P JUPITER, cholesterol efflux capacity was associated with incident CVD in individuals on potent statin therapy but not at baseline. For both baseline and on-statin analyses, HDL particle number was the strongest of 4 HDL-related biomarkers as an inverse predictor of incident events and biomarker of residual risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681. © 2017 American Heart Association, Inc.

  18. Intracoronary Compared to Intravenous Bolus Abciximab during Primary Percutaneous Coronary Intervention in ST-segment Elevation Myocardial Infarction (STEMI) Patients Reduces 30-day Mortality and Target Vessel Revascularization: A Randomized Trial

    DEFF Research Database (Denmark)

    Iversen, Allan; Abildgaard, Ulrik; Galloe, Anders

    2011-01-01

    Background: Abciximab is beneficial in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). However, the optimal administration route of the initial bolus of abciximab, that is, intravenous (IV) versus intracoronary (IC), has.......03). No significant difference in MI rates was seen (IV 4.7% vs. IC 2.7%; P = 0.32). We found a significant reduction in the composite end-point (IV 19.4% vs. IC 7.6%; P = 0.001) in favor of IC use. Major bleeding complications were similar (IV 2.4% vs. IC 1.6%; P = 0.62). Neither difference was observed in minor...... bleedings (IV 14.1% vs. IC 9.7%; P = 0.20). Conclusion: IC administration of bolus abciximab in STEMI patients undergoing pPCI reduces 30-day mortality and TVR and tends to reduce MI, compared to IV-bolus. (J Interven Cardiol 2011;24:105-111)....

  19. [Prehospital thrombolysis: A national perspective. Pharmaco-invasive strategy for early reperfusion of STEMI in Mexico].

    Science.gov (United States)

    Arriaga-Nava, Roberto; Valencia-Sánchez, Jesús-Salvador; Rosas-Peralta, Martin; Garrido-Garduño, Martin; Calderón-Abbo, Moisés

    2015-01-01

    To review the existing evidence on the role of prehospital thrombolysis in patients with ST-segment elevation acute myocardial infarction (STEMI) as part of a strategy of cutting edge to reduce the time of coronary reperfusion and as a consequence improves both the survival and function. We used the technique of exploration-reduction-evaluation-analysis and synthesis of related studies, with an overview of current recommendations, data from controlled clinical trials and from the national and international registries about the different strategies for STEMI reperfusion. In total, we examined 186 references on prehospital thrombolysis, 130 references in times door-treatment, 139 references in STEMI management and national and international registries as well as 135 references on rescue and primary percutaneous coronary intervention for STEMI. Finally the 48 references that were more relevant and informative were retained. The «time» factor is crucial in the success of early reperfusion in STEMI especially if thrombolysis is applied correctly during the prehospital time. The primary percutaneous coronary intervention is contingent upon its feasibility before 120 min from the onset of symptoms. In our midst to internationally, thrombolysis continues to be a strategy with great impact on their expectations of life and function of patients. Telecommunication systems should be incorporate in real time to the priority needs of catastrophic diseases such as STEMI where life is depending on time. Copyright © 2014 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

  20. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials

    NARCIS (Netherlands)

    Boekholdt, S. Matthijs; Hovingh, G. Kees; Mora, Samia; Arsenault, Benoit J.; Amarenco, Pierre; Pedersen, Terje R.; LaRosa, John C.; Waters, David D.; Demicco, David A.; Simes, R. John; Keech, Antony C.; Colquhoun, David; Hitman, Graham A.; Betteridge, D. John; Clearfield, Michael B.; Downs, John R.; Colhoun, Helen M.; Gotto, Antonio M.; Ridker, Paul M.; Grundy, Scott M.; Kastelein, John J. P.

    2014-01-01

    Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density

  1. Impact of statins in microalbuminuric subjects with the metabolic syndrome : a substudy of the PREVEND Intervention Trial

    NARCIS (Netherlands)

    Geluk, CA; Asselbergs, FW; Hillege, HL; Bakker, SJL; de Jong, PE; Zijlstra, F; van Gilst, WH

    Aims Microalbuminuria frequently clusters with the metabolic syndrome and may identify subjects at increased coronary risk. Statin treatment may reduce the incidence of major adverse cardiac events in subjects with the metabolic syndrome, but evidence is limited. We evaluated the impact of

  2. Role of Statin Drugs for Polycystic Ovary Syndrome

    Directory of Open Access Journals (Sweden)

    Lisa Cassidy Vu

    2017-03-01

    Full Text Available Objective: To review the potential role and specific impact of statin drugs in women with PCOS. The evidence for this use of statins in PCOS is limited and still under further investigation.Materials and methods: A search was conducted using PubMed, DynaMed and PubMedHealth databases through October 16, 2016 using the terms polycystic ovary syndrome, PCOS, hydroxymethylglutaryl-CoA reductase inhibitors, hydroxymethylglutaryl-CoA , statin, atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin. English-language trials evaluating statins in PCOS were obtained and incorporated if they provided relevant data for providers.Results: We summarize twelve trials involving statins in PCOS. The trials were predominantly 12 weeks to 3 months in length (8 of the 12 trials and low to moderate dose of statin drugs were used. The majority (10 of 12 of the trials show that statins reduce testosterone levels or other androgen hormones (DHEA-S and androstenedione, half of the trials evaluating LH/FSH ratio show an improvement, and all had positive effects on lipid profiles.Conclusion: Statins show promising improvements in serum levels of androgens and LH/FSH ratios translating to improved cardiovascular risk factors above and beyond simply lowering LDL levels. More investigation is needed to determine if statins can clinically impact women with PCOS long term, particularly those who are young and are not yet candidates for traditional preventative treatment with a statin medication. 

  3. Balancing Primary Prevention and Statin-Induced Diabetes Mellitus Prevention.

    Science.gov (United States)

    Rochlani, Yogita; Kattoor, Ajoe John; Pothineni, Naga Venkata; Palagiri, Raga Deepak Reddy; Romeo, Francesco; Mehta, Jawahar L

    2017-10-01

    Diabetes mellitus (DM), a modern-day epidemic, is a significant risk factor for cardiovascular disease. It is believed that statins elevate the risk of incident DM. Multiple trials were suggestive of the hyperglycemic effect of long-term statin use. This has prompted the Food and Drug Administration to include the risk of DM in the product label of statins. New-onset DM with statin use is biologically plausible and can be explained based on the multiple pathways in glucose metabolism affected by statins. Most pivotal clinical trials on statins were not powered to adequately assess the risk of incident DM with statin use, and the results from multiple meta-analyses are mixed. Currently, the US Preventive Services Task Force recommend the use of statins for primary prevention in patients with at least 1 cardiovascular risk factor and a 10-year risk of >7.5%. With the new American College of Cardiology/American Heart Association guidelines, the number of patients eligible for statin therapy has increased exponentially, which also calls for caution and increased vigilance in prescribing physicians regarding the controversies surrounding statin use. This article aims to highlight the existing data on statin use for primary prevention in diabetics and nondiabetics and the association of statins use with new-onset DM and its postulated mechanisms. Published by Elsevier Inc.

  4. Statin use in patients with peripheral arterial disease.

    Science.gov (United States)

    Harris, Sheena K; Roos, Matt G; Landry, Gregory J

    2016-12-01

    Statins are recommended for use in patients with peripheral arterial disease (PAD) to reduce cardiovascular events and mortality. However, much of the data regarding benefits of statins stem from the cardiovascular literature. Here, we review the literature regarding statin use specifically in patients with PAD regarding its effects on cardiovascular events and mortality, limb-related outcomes, statin use after endovascular interventions, statin dosing, and concerns about statins. We performed a literature review using PubMed for literature after the year 2000. Search terms included "statins," "peripheral arterial disease," "peripheral vascular disease," "lipid-lowering medication," and "cardiovascular disease." There is good evidence of statins lowering cardiovascular events and cardiovascular-related mortality in patients with PAD. Though revascularization rates were reduced with statins, amputation rates and amputation-free survival did not improve. Small randomized controlled trials show that patients taking statins can slightly improve pain-free walking distance or pain-free walking time, although the extent of the effect on quality of life is unclear. Statin use for patients undergoing endovascular interventions is recommended because of the reduction of postoperative cardiovascular events. Not enough data exist to support local effects of systemic statin therapy, such as prevention of restenosis. For statin dosing, there is little increased benefit to intense therapy compared with the adverse effects, whereas moderate-dose therapy has significant benefits with very few adverse effects. Adverse effects of moderate-dose statin therapy are rare and mild and are greatly outweighed by the cardiovascular benefits. There is strong evidence to support use of statins in patients with PAD to reduce cardiovascular events and mortality. Use in patients undergoing open and endovascular interventions is also recommended. Statin use may reduce the need for

  5. Statin-related myotoxicity

    OpenAIRE

    Fernandes, V; Santos, MJ; Pérez, A

    2016-01-01

    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...

  6. Remembering Statins: Do Statins Have Adverse Cognitive Effects?

    Science.gov (United States)

    Bitzur, Rafael

    2016-08-01

    The issue of statin-associated cognitive impairment has been a hot topic among both patients and health care providers, especially since the U.S. Food and Drug Administration (FDA) issued a statement regarding rare postmarketing reports of ill-defined cognitive impairment associated with statin use. This statement was based on case reports, and no objective measures of cognitive function were used. Nevertheless, many patients at high risk of cardiovascular disease have expressed concerns about possible cognitive decline and may have opted to forgo statin therapy. In this overview, the evidence leading to the statement by the FDA is reviewed. Potential mechanisms of the effect of LDL cholesterol reduction and statin therapy on cognition are discussed. Evidence from observational and prospective randomized trials is summarized, leading to the conclusion that as for now, there is no good evidence that statins cause cognitive impairment to a significant degree. Reported cases seem to be rare, and a causal relationship has not been established. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    Background HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment. Methods...... Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more. Participants were randomly allocated...... 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...

  8. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia.

    Science.gov (United States)

    Arai, Hidenori; Yamashita, Shizuya; Yokote, Koutaro; Araki, Eiichi; Suganami, Hideki; Ishibashi, Shun

    2017-06-01

    Substantial residual cardiovascular risks remain despite intensive statin treatment. Residual risks with high triglyceride and low high-density lipoprotein cholesterol are not the primary targets of statins. K-877 (pemafibrate) demonstrated robust efficacy on triglycerides and high-density lipoprotein cholesterol and a good safety profile as a monotherapy. The aim of these studies was to evaluate the efficacy and safety of K-877 add-on therapy to treat residual hypertriglyceridaemia during statin treatment. The objectives were investigated in two, multicentre, randomised, double-blind, placebo-controlled, parallel group comparison clinical trials: (A) K-877 0.1, 0.2, and 0.4 mg/day in combination with pitavastatin for 12 weeks in 188 patients, (B) K-877 0.2 (fixed dose) and 0.2 (0.4) (conditional up-titration) mg/day in combination with any statin for 24 weeks in 423 patients. In both studies, we found a robust reduction in fasting triglyceride levels by approximately 50% in all combination therapy groups, which was significant compared to the statin-monotherapy (placebo) groups (p K-877 add-on therapy, i.e. small low-density lipoproteins decreased whereas larger ones increased, and larger high-density lipoproteins decreased whereas smaller ones increased. The incidence rates of adverse events and adverse drug reactions in K-877 combination therapy groups were comparable to those in 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.

  9. Osteoprotegerin Levels Change During STEMI and Reflect Cardiac Function

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan Skov; Hoffmann, Søren

    2014-01-01

    of OPG levels during STEMI treated with percutaneous coronary intervention (PCI) and additionally, the effect of OPG levels on cardiac function. METHODS: We prospectively included 42 patients with STEMI treated with primary PCI. Four consecutive blood samples were obtained before and after PCI treatment...

  10. Safety of statins

    Directory of Open Access Journals (Sweden)

    Debasish Maji

    2013-01-01

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

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

    Science.gov (United States)

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

    2010-07-31

    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

  12. STATIN SAFETY REVISITED DATA

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2013-01-01

    Full Text Available Questions of statins use in liver diseases are discussed. Data from clinical studies on statins safety in cardiac patients with liver diseases are presented. Features of statins use in nonalcoholic fatty liver disease, viral hepatitis C are considered separately.

  13. Management of statin intolerance

    Directory of Open Access Journals (Sweden)

    Soma B Raju

    2013-01-01

    Full Text Available Statins are the revolutionary drugs in the cardiovascular pharmacotherapy. But they also possess several adverse effects like myopathy with elevation of hepatic transaminases (>3 times the upper limit of normal or creatine kinase (>10 times the upper limit of normal and some rare side-effects, including peripheral neuropathy, memory loss, sleep disturbances, and erectile dysfunction. Due to these adverse effects, patients abruptly withdrew statins without consulting physicians. This abrupt discontinuation of statins is termed as statin intolerance. Statin-induced myopathy constitutes two third of all side-effects from statins and is the primary reason for statin intolerance. Though statin intolerance has considerably impacted cardiovascular outcomes in the high-risk patients, it has been well effectively managed by prescribing statins either as alternate-day or once weekly dosage regimen, as combination therapy with a non-statin therapy or and by dietary intervention. The present article reviews the causes, clinical implications of statin withdrawal and management of statin intolerance.

  14. Statins and risk of diabetes mellitus

    Directory of Open Access Journals (Sweden)

    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

  15. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial.

    Science.gov (United States)

    Nissen, Steven E; Stroes, Erik; Dent-Acosta, Ricardo E; Rosenson, Robert S; Lehman, Sam J; Sattar, Naveed; Preiss, David; Bruckert, Eric; Ceška, Richard; Lepor, Norman; Ballantyne, Christie M; Gouni-Berthold, Ioanna; Elliott, Mary; Brennan, Danielle M; Wasserman, Scott M; Somaratne, Ransi; Scott, Rob; Stein, Evan A

    2016-04-19

    Muscle-related statin intolerance is reported by 5% to 20% of patients. To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7% (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg

  16. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab

    NARCIS (Netherlands)

    Stroes, Erik; Colquhoun, David; Sullivan, David; Civeira, Fernando; Rosenson, Robert S.; Watts, Gerald F.; Bruckert, Eric; Cho, Leslie; Dent, Ricardo; Knusel, Beat; Xue, Allen; Scott, Rob; Wasserman, Scott M.; Rocco, Michael

    2014-01-01

    This study sought to evaluate the efficacy and safety of subcutaneous evolocumab compared with oral ezetimibe in hypercholesterolemic patients who are unable to tolerate effective statin doses. Statin intolerance, which is predominantly due to muscle-related side effects, is reported in up to 10% to

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

    NARCIS (Netherlands)

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

    2017-01-01

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

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

    Science.gov (United States)

    Saxon, David R; Eckel, Robert H

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

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

    Science.gov (United States)

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

    2016-04-19

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

  20. Statins for aortic valve stenosis.

    Science.gov (United States)

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

    2016-01-01

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

  1. Relative safety profiles of high dose statin regimens

    Directory of Open Access Journals (Sweden)

    Carlos Escobar

    2008-06-01

    Full Text Available Carlos Escobar, Rocio Echarri, Vivencio BarriosDepartment of Cardiology, Hospital Ramón y Cajal, Madrid, SpainAbstract: Recent clinical trials recommend achieving a low-density lipoprotein cholesterol level of <100 mg/dl in high-risk and <70 mg/dl in very high risk patients. To attain these goals, however, many patients will need statins at high doses. The most frequent side effects related to the use of statins, myopathy, rhabdomyolysis, and increased levels of transaminases, are unusual. Although low and moderate doses show a favourable profile, there is concern about the tolerability of higher doses. During recent years, numerous trials to analyze the efficacy and tolerability of high doses of statins have been published. This paper updates the published data on the safety of statins at high doses.Keywords: statins, high doses, tolerability, liver, muscle

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  3. Rosuvastatin for Primary Prevention Among Individuals With Elevated High-Sensitivity C-Reactive Protein and 5% to 10% and 10% to 20% 10-Year Risk Implications of the Justification for Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial for "Intermediate Risk"

    NARCIS (Netherlands)

    Ridker, Paul M.; Macfadyen, Jean G.; Nordestgaard, Børge G.; Koenig, Wolfgang; Kastelein, John J. P.; Genest, Jacques; Glynn, Robert J.

    2010-01-01

    Background-Recent primary prevention guidelines issued in Canada endorse the use of statin therapy among individuals at "intermediate risk" who have elevated levels of high-sensitivity C-reactive protein (hsCRP). However, trial data directly addressing whether this recommendation defines a patient

  4. Statin resistance and export

    DEFF Research Database (Denmark)

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    -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. Statin Intolerance: the Clinician's Perspective.

    Science.gov (United States)

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

    2015-12-01

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

  7. Statin-related myotoxicity.

    Science.gov (United States)

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

    2016-05-01

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

  8. [Statins in primary prevention of cardiovascular disease].

    Science.gov (United States)

    Adham, S; Miranda, S; Doucet, J; Lévesque, H; Benhamou, Y

    2018-01-01

    Cardiovascular events are the second leading cause of death in France. The assessment of overall cardiovascular risk using a personalized assessment with weighting risk factors can predict the risk of cardiovascular events in ten years. The validated treatments to reduce cardiovascular mortality in primary prevention are few. The use of statins in primary prevention is discussed. We report in this review the updated conclusions from clinical trials regarding the treatment with statins in primary prevention. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  9. Do statins protect against upper gastrointestinal bleeding?

    DEFF Research Database (Denmark)

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

    2009-01-01

    AIMS: Recently, an apparent protective effect of statins against upper gastrointestinal bleeding (UGB) was postulated in a post hoc analysis of a randomized trial. We aimed to evaluate the effect of statin use on acute nonvariceal UGB alone or in combinations with low-dose aspirin and other...... antithrombotic drugs. METHODS: A population-based case-control study was conducted in the County of Funen, Denmark. Cases (n = 3652) were all subjects with a first discharge diagnosis of serious UGB from a hospital during the period 1995 to 2006. Age- and gender-matched controls (10 for each case) (n = 36 502...... significant protective effect was observed for concurrent users of low-dose aspirin [OR 0.43 (0.18-1.05)]. CONCLUSION: Statins do not prevent UGB, except possibly in users of low-dose aspirin....

  10. Considerations for supplementing with coenzyme Q10 during statin therapy.

    Science.gov (United States)

    Levy, Hedva Barenholtz; Kohlhaas, Heather K

    2006-02-01

    To review the literature concerning the effects of statin use on coenzyme (Co) Q10 concentrations and explain the rationale behind considering CoQ10 supplementation. A MEDLINE search was conducted through January 2006. Search terms included ubiquinone, coenzyme Q10, HMG-CoA reductase inhibitors, statins, myotoxicity, and clinical trials. Statin therapy reduces blood CoQ10 concentrations. Studies exploring how this affects the development of myotoxicity have been small and dissimilar, thus limiting the ability to draw strong conclusions. Isolated studies suggested that statins induce mitochondrial dysfunction, but the clinical implications of this effect are limited. Limited data suggest that patients with familial hypercholesterolemia, heart failure, or who are over 65 years of age might represent at-risk populations who would benefit from CoQ10 supplementation. Routine CoQ10 supplementation for all patients taking statins to prevent myotoxicity is not recommended. However, certain subpopulations might be at risk and warrant further study.

  11. Statins: Cholesterol guidelines and Indian perspective

    Directory of Open Access Journals (Sweden)

    Anil S Menon

    2015-01-01

    Full Text Available Statins have become an important drug in preventing the occurrence of atherosclerotic cardiovascular disease (ASCVD. The effectiveness of statins in reducing ASCVD has been established in large-scale clinical trials. The lipid management guidelines have been periodically modified due to accumulating evidence about the proportionate benefit achieved with a progressive reduction in cholesterol levels with higher doses of statins and even in those at low risk of development of ASCVD. The current American College of Cardiology/American Heart Association guidelines have based its recommendations from data gathered exclusively from randomized controlled trials. It has simplified the use of statins, but also raised questions regarding the validity of its cardiovascular event risk prediction tool. Epidemiology of cardiovascular disease in India differs from the western population; there is an increased the prevalence of metabolic syndrome and atherogenic dyslipidemia phenotype a group not addressed in the current guidelines. The guidelines are based on trials, which do not have a representative South Asian population. This article reviews the relevant literature, and examines the issues involved in adopting the guidelines to the Indian population.

  12. STEMI vs NSTEACS management trends in non-invasive hospital

    Directory of Open Access Journals (Sweden)

    Abdulhalim Jamal Kinsara

    2016-07-01

    Conclusion: NSTEACS patients in western province of KSA present at an older age are mostly males and have higher prevalence of hypertension and hyperlipidemia compared with STEMI patients. It is therefore important to identify patients with high-risk profile and put implement measures to reduce these factors.

  13. Controlling Cholesterol with Statins

    Science.gov (United States)

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

  14. Statins: pros and cons.

    Science.gov (United States)

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

    2017-12-29

    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.

  15. Statins and polyneuropathy revisited

    DEFF Research Database (Denmark)

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

    2017-01-01

    "); current use was further classified into long-term use (5+ years) and high or low intensity use. We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to examine associations between polyneuropathy and statin use. RESULTS: We included 370 validated cases...... and 7400 controls. Ever use of statins was not associated with elevated risk of polyneuropathy (OR: 1.14, 95%CI: 0.84-1.54). Similarly, we found no associations between polyneuropathy risk and current use (OR: 1.11, 95% CI: 0.79-1.53), long-term use (OR: 1.13, 95%CI: 0.66-1.92), or high intensity statin......AIM: In a previous study, we found a positive association between statin use and polyneuropathy risk. Other studies reported equivocal results. The present study aimed to confirm our findings with a design similar to our previous study, but with a larger data set. METHODS: We searched medical...

  16. How to take statins

    Science.gov (United States)

    ... Raising HDL (good) cholesterol in your blood Lowering triglycerides , another type of fat in your blood Statins ... gov/pubmed/26299317 . Semenkovich CF Disorders of lipid metabolism. In: Goldman L, Schafer AI, eds. Goldman's Cecil ...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

    Scale, Barthel Index, and modified Rankin Scale score at enrollment (1 to 6 months after the index event) and 90 days poststroke in subjects having a stroke during the trial. RESULTS: Over 4.9 years, strokes occurred in 576 subjects. There were reductions in fatal, severe (modified Rankin Scale score 5...... or no event), there was only a trend toward lesser severity with treatment based on the modified Rankin Scale score (P=0.0647) with no difference based on the National Institutes of Health Stroke Scale or Barthel Index. CONCLUSIONS: The present exploratory analysis suggests that the outcome of recurrent...... 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

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

    Science.gov (United States)

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

    2012-01-01

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

  19. Recent findings on the health effects of omega-3 fatty acids and statins, and their interactions: do statins inhibit omega-3?

    Directory of Open Access Journals (Sweden)

    de Lorgeril Michel

    2013-01-01

    Full Text Available Abstract Early randomized controlled trials (RCTs demonstrated the health benefits of omega-3 fatty acids (n-3, whereas recent RCTs were negative. We now address the issue, focusing on the temporal changes having occurred: most patients in recent RCTs are no longer n-3 deficient and the vast majority are now treated with statins. Recent RCTs testing n-3 against arrhythmias suggest that n-3 reduce the risk only in patients not taking a statin. Other recent RCTs in secondary prevention were negative although, in a post-hoc analysis separating statin users and non-users, non-significant protection of n-3 was observed among statin non-users whereas statin users had no effect. Recent RCTs testing statins - after the implementation of the New Clinical Trial Regulation in 2007 - are negative (or flawed suggesting that the lack of effect of n-3 cannot be attributed to a parallel protection by statins. Finally, statins favor the metabolism of omega-6 fatty acids (n-6, which in turn inhibits n-3 and, contrary to n-3, they increase insulin resistance and the risk of diabetes. Thus, n-3 and statins are counteractive at several levels and statins appear to inhibit n-3.

  20. Rationale and design of a trial on the effect of high dose statins on cardiovascular risk in adults after successful coarctation repair

    NARCIS (Netherlands)

    Luijendijk, Paul; Bouma, Berto J.; Vriend, Joris W. J.; Groenink, Maarten; Vliegen, Hubert W.; de Groot, Eric; Pieper, Petronella G.; van Dijk, Arie P. J.; Sieswerda, Gertjan T.; Veen, Gerrit; Zwinderman, Aeilko H.; Mulder, Barbara J. M.

    Background: HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful

  1. Rationale and design of a trial on the effect of high dose statins on cardiovascular risk in adults after successful coarctation repair.

    NARCIS (Netherlands)

    Luijendijk, P.; Bouma, B.J.; Vriend, J.W.; Groenink, M.; Vliegen, H.W.; Groot, E. de; Pieper, P.G.; Dijk, A.P.J. van; Sieswerda, G.T.; Veen, G.; Zwinderman, A.H.; Mulder, B.J.

    2012-01-01

    BACKGROUND: HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful

  2. Rationale and design of a trial on the effect of high dose statins on cardiovascular risk in adults after successful coarctation repair

    NARCIS (Netherlands)

    Luijendijk, Paul; Bouma, Berto J.; Vriend, Joris W. J.; Groenink, Maarten; Vliegen, Hubert W.; de Groot, Eric; Pieper, Petronella G.; van Dijk, Arie P. J.; Sieswerda, Gertjan T.; Veen, Gerrit; Zwinderman, Aeilko H.; Mulder, Barbara J. M.

    2012-01-01

    Background: HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful

  3. 3ST-POL trial: standards of statin use in Poland in the context of the European Society of Cardiology guidelines.

    Science.gov (United States)

    Sliz, Daniel; Mamcarz, Artur; Filipiak, Krzysztof J; Siebert, Janusz; Naruszewicz, Marek

    2010-09-01

    Statins play a crucial role in modern cardiological pharmacotherapy. For the patient, as the beneficiary of an effective pharmacotherapy, it is of utmost importance that his or her physician can take maximum advantage of the whole potential of the available medications. The aim of the study was to analyse the effectiveness of statin treatment in Polish patients treated in an ambulatory setting, in view of the European Society of Cardiology guidelines. The study was conducted on 49,950 ambulatory patients from Poland (women--53%, men--47%). The questionnaire consisted of 43 questions and was completed by a physician based on the results of physical examination, medical records, lipid profile, and additional tests. Twenty-eight per cent of the patients were obese, 37% were overweight, and more than 26% were smokers. The mean blood pressure was 142.9/84.0 mmHg (±18.5/11.6 mmHg). The target objectives of the pharmacological treatment of arterial hypertension were achieved in less than 25% of the study population. Nearly 50% of the patients had coronary artery disease, 20% had myocardial infarction, and 10% had transient ischemic attack or cerebral stroke. More than 30% of the patients had diabetes mellitus. The most commonly used statins were atorvastatin and simvastatin (49.1% vs. 44.8%, respectively; P <0.05). Almost 71% of the patients received the daily statin dose of <20 mg. Mean total cholesterol (TC) was 244.9 mg/dl, low-density lipoprotein (LDL) cholesterol--55 mg/dl, and triglycerides--180 mg/dl. TC levels of <190 mg/dl were achieved in 1 in 6 patients, and LDL levels of <115 mg/dl in less than 21% of the patients. Despite the recommendation to administer statins at higher than minimum doses in primary and secondary prevention of coronary heart disease, this drug class is still underestimated by general practitioners.

  4. Pleiotropic effects of statins

    Directory of Open Access Journals (Sweden)

    Narasaraju Kavalipati

    2015-01-01

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

  5. Plasma glucose and not hemoglobin or renal function predicts mortality in patients with STEMI complicated with cardiogenic shock

    NARCIS (Netherlands)

    Vis, Marije M.; Engström, Annemarie E.; Sjauw, Krischan D.; Tjong, Fleur Vy; Baan, Jan; Koch, Karel T.; de Vries, Hans J.; Tijssen, Jan Gp; de Winter, Robbert J.; Piek, Jan J.; Henriques, José Ps

    2010-01-01

    Objective To assess the predictive value of three biomarkers for mortality in ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock. Background STEMI complicated by cardiogenic shock accounts for the majority of STEMI related deaths. Patients with STEMI and hyperglycemia, anemia

  6. Evaluation of a primary care paramedic STEMI bypass guideline.

    Science.gov (United States)

    Kwong, Jonathan L; Ross, Garry; Turner, Linda; Olynyk, Chris; Cheskes, Sheldon; Thurston, Adam; Verbeek, P Richard

    2017-11-20

    Limited evidence supports primary care paramedic (PCP) direct transport of ST-segment elevation myocardial infarction (STEMI) patients for percutaneous coronary intervention (PCI). The goal of this study was to evaluate an urban-based PCP STEMI bypass guideline. We reviewed consecutive Toronto Paramedic Services call reports between April 7, 2015, and May 31, 2016, regarding STEMI patients identified by PCPs. The primary outcome was patient assignment (stable versus unstable) according to guideline criteria. Secondary outcomes were the proportion of PCP-transported patients who had an indication for an advanced care intervention (ACI) or who received an ACI when PCPs rendezvoused with an advanced care paramedic (ACP). Lastly, we reviewed prehospital outcomes of cardiac arrest patients and calculated the difference in transport intervals between direct PCP bypass and a PCI-centre and predicted transport interval to the closest emergency department (ED). Of 361 patients, 232 were PCP transports and 129 were ACP-rendezvous transports. There was a significant difference in the distribution of stable and unstable patients between PCPs and ACPs (p<0.001). For PCP patients, 21/232 (9.1%) had indications for an ACI, whereas 34/129 (26.4%) ACP patients received an ACI. Eleven patients experienced cardiac arrest; 10 were successfully resuscitated (5 of these by PCPs). The median difference between direct PCP bypass and a PCI-centre versus transport to the closest ED was 5.53 minutes (IQR=6.71). We found a significant difference in the distribution of stable and unstable patients and fewer patients with indications for an ACI in PCP patients. This PCP STEMI bypass guideline appears feasible.

  7. Elderly patients with STEMI are suboptimally treated with reperfusion therapy

    Czech Academy of Sciences Publication Activity Database

    Monhart, Z.; Faltus, Václav; Grünfeldová, Hana; Janský, P.

    2008-01-01

    Roč. 117, č. 19 (2008), s. 79-79 ISSN 0009-7322. [The 2008 World Congress on Cardiology. 18.05.2008-21.05.2008, Buenos Aires] R&D Projects: GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z10300504 Keywords : acute myocardial infarction * primary reprefusion therapy * STEMI Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery

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

    Science.gov (United States)

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

    2015-01-01

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

  9. Genetically Guided Statin Therapy

    Science.gov (United States)

    2017-03-01

    outcomes known to be prevented by statin therapy, we examined hospitalizations for three diagnoses: acute myocardial infarction (MI), stroke, and...0.84 Tobacco 0.051368 (736) 0.043552 (5418) 1.69E-05 Follow-Up (days) 1325.7711 1260.4477 əe-20 Product Strength (mg) 45.9049 43.6006 0.000923...cholesterol. However, the ultimate goal of statin therapy is to decrease incidence of CAD, acute myocardial infarction and perhaps stroke. However, there is a

  10. Statins and oxidative stress in the cardiovascular system.

    Science.gov (United States)

    Margaritis, Marios; Sanna, Fabio; Antoniades, Charalambos

    2017-09-26

    Statins are widely established as an important class of medications for primary and secondary prevention of cardiovascular disease. In addition to their lipid-lowering effects, mounting evidence suggests that statins exhibit non-lipid-lowering mediated effects in the cardiovascular system. These so called "pleiotropic" effects are partly due to antioxidant properties of statins. These are mediated by inhibition of the mevalonate pathway, which interferes with small GTP-ase protein prenylation. This, in turn, leads to anti-oxidant effects of statins via a plethora of mechanisms. Statins prevent the activation of the pro-oxidant enzyme NADPH-oxidase by interfering with Rac1 activation and translocation to the membrane, as well as reducing expression of crucial subunits of NADPH-oxidase. Statins also enhance the expression, enzymatic activity and coupling of endothelial nitric oxide synthase (eNOS), through mevalonate-dependent effects. The net result is a restoration of the redox balance in the cardiovascular system, with subsequent anti-atherosclerotic and cardioprotective effects. While the evidence from basic science studies and animal models is strong, more clinical trials are required to establish the relevance of these pleiotropic effects to human cardiovascular disease and potentially lead to expanded indications for statin treatment or alternative therapeutic strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  11. Salvia officinalis (Sage) Leaf Extract as Add-on to Statin Therapy in Hypercholesterolemic Type 2 Diabetic Patients: a Randomized Clinical Trial

    OpenAIRE

    Kianbakht, Saeed; Nabati, Farzaneh; Abasi, Behrooz

    2016-01-01

    The efficacy and safety of Salvia officinalis combined with statin have not been evaluated in dyslipidemic diabetes mellitus type 2 (DDMT2) so far. The plant extract antioxidant activity was determined by the DPPH radical scavenging assay. The total flavonoid, total phenolic and quercetin contents of the capsules containing the plant extract were also measured. Moreover, the effects of 2-month extract intake (500 mg capsule three times a day) as add-on to daily use of 15 mg glyburide, 2000 mg...

  12. Reviewing statin therapy in diabetes--towards the best practise.

    Science.gov (United States)

    Matikainen, Niina; Kahri, Juhani; Taskinen, Marja-Riitta

    2010-04-01

    Statin therapy is considered critical both in primary and secondary prevention of cardiovascular disease in diabetes. Cholesterol Treatment Trialists' Collaborators meta-analysis of 14 randomised trials of statins in 18686 people with diabetes provides the latest and largest evidence showing a significant 21% reduction in major vascular events per mmol/l reduction in LDL cholesterol. Importantly, the risk reduction was similar in both types of diabetes. Growing evidence supports the view that statin therapy reduces microvascular complications as well. This review updates the current knowledge of statin therapy in preventing micro- and macrovascular complications in both type 1 and type 2 diabetes. (c) 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2016-05-01

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

  14. Statins for the prevention of dementia.

    Science.gov (United States)

    McGuinness, Bernadette; Craig, David; Bullock, Roger; Passmore, Peter

    2016-01-04

    This is an update of a Cochrane review first published in 2001 and then updated in 2009. Vascular risk factors including high cholesterol levels increase the risk of dementia due to Alzheimer's disease and of vascular dementia. Some observational studies have suggested an association between statin use and lowered incidence of dementia. To evaluate the efficacy and safety of statins for the prevention of dementia in people at risk of dementia due to their age and to determine whether the efficacy and safety of statins for this purpose depends on cholesterol level, apolipoprotein E (ApoE) genotype or cognitive level. We searched ALOIS (the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS, ClinicalTrials.gov and the World Health Organization (WHO) Portal on 11 November 2015. We included double-blind, randomised, placebo-controlled trials in which statins were administered for at least 12 months to people at risk of dementia. We used standard methodological procedures expected by Cochrane. We included two trials with 26,340 participants aged 40 to 82 years of whom 11,610 were aged 70 or older. All participants had a history of, or risk factors for, vascular disease. The studies used different statins (simvastatin and pravastatin). Mean follow-up was 3.2 years in one study and five years in one study. The risk of bias was low. Only one study reported on the incidence of dementia (20,536 participants, 31 cases in each group; odds ratio (OR) 1.00, 95% confidence interval (CI) 0.61 to 1.65, moderate quality evidence, downgraded due to imprecision). Both studies assessed cognitive function, but at different times using different scales, so we judged the results unsuitable for a meta-analysis. There were no differences between statin and placebo groups on five different cognitive tests (high quality evidence). Rates of treatment discontinuation due to non-fatal adverse events were

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

    NARCIS (Netherlands)

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

    2016-01-01

    Recent evidence suggests that statin intolerance may be more common than reported in randomized trials. However, the statin-intolerant population is not well characterized. The goal of this report is to characterize the population enrolled in the phase 3 Goal Achievement after Utilizing an

  16. LIFESTAT – Living with statins

    DEFF Research Database (Denmark)

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

    2016-01-01

    % 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....... 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...

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

    Science.gov (United States)

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

    2015-01-01

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

  18. Persisting weakness after withdrawal of a statin.

    Science.gov (United States)

    Mygland, Åse; Ljøstad, Unn; Krossnes, Bård Kronen

    2014-04-08

    An 81-year-old woman treated with simvastatin for several years followed by atorvastatin for about 1 year presented with fatigue, weakness and unsteady gait. The finding of elevated creatine kinase (CK) and symmetric muscle weakness around shoulders and hips led to suspicion of a toxic statin-associated myopathy. Atorvastatin was withdrawn, but her weakness persisted. Owing to persisting weakness, an autoimmune myopathy (myositis) was suspected, but initially disregarded since a muscle biopsy showed necrotic muscle fibres without inflammatory cell infiltrates and myositis-specific autoantibodies were absent. After 18 months with slowly progressive weakness and increasing CK values, awareness of new knowledge about autoimmunity as a cause of necrotic myopathy, led to a successful treatment trial with intravenous immunoglobulines, followed by steroids and metothrexate. Antibodies to the target enzyme of statins (HMGCR (3-hydroksy-3-methylglutaryl-coenzyme A reductase)) were detected in her serum, and she was diagnosed with autoimmune necrotic myositis probably triggered by atorvastatin.

  19. [Effects of different statins, ezetimibe/simvastatin combination on hsCRP levels in unstable angina pectoris and non-ST elevation myocardial infarction patients: a randomized trial].

    Science.gov (United States)

    Namal, Esat; Sener, Nur; Ulaş, Turgay; Akçalı, Zafer; Oztekin, Erkan; Borlu, Fatih

    2011-12-01

    The aim of our study was to evaluate the effects of two different statins and a statin/ezetimibe combination on high sensitive C-reactive protein (hsCRP) values, which were given at high doses in the early period of acute coronary syndromes. A total of 150 patients with non-ST elevation myocardial infarction and unstable angina pectoris were enrolled to our prospective, randomized, single-blind study. Patients were divided into three groups by block randomization method. One group received 20 mg/day atorvastatin, one group received 10 mg/day rosuvastatin and the other group received 10 mg/day ezetimibe/simvastatin combination therapy, which was initiated within the first 24 hours of admission. Follow-up duration was 2 months . Biochemical investigations and hsCRP levels (by nephelometric method) were performed with 138 patients evaluated at baseline, 10th and 60th days of therapy. Decreases of hsCRP levels were analyzed with one-way MANOVA and repeated measures of ANOVA methods. Post-hoc Tukey HSD test was performed for finding the different group, when the difference was detected between the groups. Tenth day hsCRP levels in ezetimibe/simvastatin group was significantly lower than the other groups (punstable angina and non ST elevation myocardial infarction.

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

    Science.gov (United States)

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

    2016-06-01

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

  1. [Statins diabetogenicity: are all the same? state of art].

    Science.gov (United States)

    Rius Tarruella, Joan; Millán Núñez-Cortés, Jesús; Pedro-Botet, Juan; Pintó Sala, Xavier

    2015-01-01

    Statins are the cornerstone of cardiovascular prevention for general population, and in patients with type 2 diabetes mellitus (T2DM). However, statin therapy predisposes to type 2 diabetes, particularly in patients with predisposition to this condition. Some statins have been associated with increases in blood glucose in patients with or without DM2, and others have shown to have neutral effects, varying from one another their glucose or diabetogenic capacity. In many statin trials the incidence of DM2 has not been systematically evaluated and others the power to detect differences between statins is lacking. Evidence highest quality available comes from the meta-analysis of controlled clinical trials. The only controlled clinical trial to evaluate the incidence of new-onset T2DM is the J-PREDICT conducted with pitavastatin in patients with abnormal glucose tolerance. Preliminary results of this study show that pitavastatin is associated with a significant decrease in the incidence of de novo T2DM compared to only modification lifestyle. Therefore, pitavastatin may be an appropriate therapeutic alternative of choice to reduce vascular risk in patients with T2DM or at risk of presenting it. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  2. Area at risk and collateral circulation in a first acute myocardial infarction with occluded culprit artery. STEMI vs non-STEMI patients.

    Science.gov (United States)

    Figueras, Jaume; Otaegui, Imanol; Marti, Gerard; Domingo, Enric; Bañeras, Jordi; Barrabés, José A; Del Blanco, Bruno Garcia; Garcia-Dorado, David

    2018-05-15

    It is unclear why among patients with first acute myocardial infarction and an occluded culprit artery only some present ST segment elevation. In fact, there is no study that compares the angiographic area at risk and the collateral circulation in first NSTEMI vs STEMI patients. 205 patients admitted for myocardial infarction with occluded culprit artery were included, 132 STEMI and 73 NSTEMI. Demographic data, the area at risk determined by the BARI score and collateral supply by the Rentrop score from the 2 groups were compared. NSTEMI patients showed lower peak Tn I than STEMI in the overall group but also in the 3 subsets with different culprit arteries (p collaterals (Rentrop score ≥ 2, 1.82 vs 0.41, p collateral blood supply than STEMI patients in each of the 3 main culprit arteries. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Treating statin-intolerant patients

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    Pigna G

    2011-04-01

    Full Text Available Marcello Arca, Giovanni PignaAtherosclerosis Unit, Department of Internal Medicine and Allied Medical Specialities, Sapienza University of Rome, Rome, ItalyAbstract: Statins are effective in reducing cardiovascular events and are safe for almost all patients. Nevertheless, intolerance to statins is frequently faced in clinical practice. This is mostly due to muscular symptoms (myalgia with or without increase of plasma creatinine kinase and/or elevation of hepatic aminotransferases, which overall constitutes approximately two-thirds of reported adverse events during statin therapy. These side effects raise concerns in patients as well as in doctors and are likely to reduce patients' adherence and, as a consequence, the cardiovascular benefit. Therefore, it is mandatory that clinicians improve their knowledge on the clinical aspects of muscular and hepatic side effects of statin therapy as well as their ability to manage patients with statin intolerance. Besides briefly examining the clinical aspects and the mechanisms that are proposed to be responsible for the most common statin-associated side effects, the main purpose of this article is to review the available approaches to manage statin-intolerant patients. The first step is to determine whether the adverse events are indeed related to statin therapy. If so, lowering the dosage or changing statin, alternate dosing options, or the use of nonstatin compounds may be practical strategies. The cholesterol-lowering potency as well as the usefulness of these different approaches in treating statin-intolerant patients will be examined based on currently available data. However, the cardiovascular benefit of these strategies has not been well established, so their use has to be guided by a careful clinical assessment of each patient.Keywords: statin therapy, atorvastatin, rosuvastatin, aminotransferase levels, myopathy

  4. Framework for a National STEMI Program: Consensus document developed by STEMI INDIA, Cardiological Society of India and Association Physicians of India

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    Thomas Alexander

    2015-09-01

    Full Text Available The health care burden of ST elevation myocardial infarction (STEMI in India is enormous. Yet, many patients with STEMI can seldom avail timely and evidence based reperfusion treatments. This gap in care is a result of financial barriers, limited healthcare infrastructure, poor knowledge and accessibility of acute medical services for a majority of the population. Addressing some of these issues, STEMI India, a not-for-profit organization, Cardiological Society of India (CSI and Association Physicians of India (API have developed a protocol of “systems of care” for efficient management of STEMI, with integrated networks of facilities. Leveraging newly-developed ambulance and emergency medical services, incorporating recent state insurance schemes for vulnerable populations to broaden access, and combining innovative, “state-of-the-art” information technology platforms with existing hospital infrastructure, are the crucial aspects of this system. A pilot program was successfully employed in the state of Tamilnadu. The purpose of this article is to describe the framework and methods associated with this programme with an aim to improve delivery of reperfusion therapy for STEMI in India. This programme can serve as model STEMI systems of care for other low-and-middle income countries.

  5. Efficacy and Safety of Adding Omega-3 Fatty Acids in Statin-treated Patients with Residual Hypertriglyceridemia: ROMANTIC (Rosuvastatin-OMAcor iN residual hyperTrIglyCeridemia), a Randomized, Double-blind, and Placebo-controlled Trial.

    Science.gov (United States)

    Kim, Chee Hae; Han, Kyung Ah; Yu, Jaemyung; Lee, Sang Hak; Jeon, Hui Kyung; Kim, Sang Hyun; Kim, Seok Yeon; Han, Ki Hoon; Won, Kyungheon; Kim, Dong-Bin; Lee, Kwang-Jae; Min, Kyungwan; Byun, Dong Won; Lim, Sang-Wook; Ahn, Chul Woo; Kim, SeongHwan; Hong, Young Joon; Sung, Jidong; Hur, Seung-Ho; Hong, Soon Jun; Lim, Hong-Seok; Park, Ie Byung; Kim, In Joo; Lee, Hyoungwoo; Kim, Hyo-Soo

    2018-01-01

    The purpose of this study was to examine the efficacy and safety of adding ω-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment. This study was a multicenter, randomized, double-blind, placebo-controlled study. After a 4-week run-in period of rosuvastatin treatment, the patients who had residual hypertriglyceridemia were randomized to receive rosuvastatin 20 mg/d plus ω-3 fatty acids 4 g/d (ROSUMEGA group) or rosuvastatin 20 mg/d (rosuvastatin group) with a 1:1 ratio and were prescribed each medication for 8 weeks. A total of 201 patients were analyzed (mean [SD] age, 58.1 [10.7] years; 62.7% male). After 8 weeks of treatment, the percentage change from baseline in triglycerides (TGs) and non-HDL-C was significantly greater in the ROSUMEGA group than in the rosuvastatin group (TGs: -26.3% vs -11.4%, P < 0.001; non-HDL-C: -10.7% vs -2.2%, P = 0.001). In the linear regression analysis, the lipid-lowering effect of ω-3 fatty acids was greater when baseline TG or non-HDL-C levels were high and body mass index was low. The incidence of adverse events was not significantly different between the 2 groups. In patients with residual hypertriglyceridemia despite statin treatment, a combination of ω-3 fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C than rosuvastatin alone. Further study is needed to determine whether the advantages of this lipid profile of ω-3 fatty acids actually leads to the prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Diagnostic performance and system delay using telemedicine for prehospital diagnosis in triaging and teatment of STEMI

    DEFF Research Database (Denmark)

    Rasmussen, Martin Bøhme; Frost, Lars; Stengaard, Carsten

    2014-01-01

    percutaneous coronary intervention (PPCI)). There are limited data on achievable system delays in an optimal STEMI system of care using prehospital diagnosis to triage patients with STEMI directly to percutaneous coronary intervention (PCI) centres. We examined the proportion of tentative prehospital STEMI...... diagnoses established by telemedicine confirmed on hospital arrival, and we determined system delay in patients diagnosed before hospital arrival and triaged directly to the catheterisation laboratory. Methods: Design: Population-based follow-up study. Setting: Central Denmark Region. Participants: 15 992...... patients diagnosed using telemedicine. Results: During the study period, a tentative diagnosis of STEMI was established in 1061 patients, of whom 919 were triaged directly to the PCI centre. In 771 (84%) patients, a diagnosis of STEMI was confirmed. Patients transported

  7. Genetic determinants of statin intolerance

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    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.

  8. STATINS AND MYOPATHY: MOLECULAR MECHANISMS

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    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. 

  9. Omega-3 index and smoking in patients with acute ST-elevation myocardial infarction taking statins: a case-control study in Korea

    Directory of Open Access Journals (Sweden)

    Kim Young

    2012-03-01

    Full Text Available Abstract Background n-3 fatty acids and lifestyle also are closely related to risk of CVD. Most Koreans have higher fish consumption than people of Western populations. However, little is known about the recommended value of omega-3 index in Korean patients with acute ST-elevation myocardial infarction (STEMI taking statins. Here, we tested the hypothesis that lower omega-3 fatty acids and/or smoking are associated with acute STEMI, even though patients with dyslipidemia who were taking statins and who attained their LDL-C goals. Methods We conducted a case-control study in which omega-3 fatty acids and lifestyle factors were determined in 24 consecutive Korean patients taking statins with angiographically confirmed acute STEMI and 68 healthy controls without acute STEMI. The omega-3 index was calculated by the sum of eicosapentaenoic acid and docosahexaenoic acid in erythrocyte membranes. Multivariable adjusted regression analysis was used to assess independent associations between acute STEMI, omega-3 index, and lifestyle factors after adjusting for age, sex, and body mass index (BMI. Results The mean age of total subjects was 59.9 years, and 57.6% of the subjects were male. The omega-3 index was significantly lower in cases (8.83% than controls (11.13%; P trans-fatty acids were not different between the two groups. The omega-3 index was inversely associated with odds for being a case (OR 0.16 (95% CI 0.03-1.14; P = 0.047, while smoking was positively associated with odds for being a case (OR 6.67 (95% CI 1.77-25.23; P = 0.005 after adjusting for all confounding variables. Conclusion This study shows that relative to controls, acute STEMI cases are more likely to be smokers and to have a lower omega-3 index, even though the cases were taking statins. An omega-3 index of at least 11% and abstinence from smoking are associated with cardioprotection for Koreans.

  10. Immune-mediated statin myopathy.

    Science.gov (United States)

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

    2016-01-01

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

  11. The nocebo effect in the context of statin intolerance.

    Science.gov (United States)

    Tobert, Jonathan A; Newman, Connie B

    2016-01-01

    The nocebo effect, the inverse of the placebo effect, is a well-established phenomenon that is under-appreciated in cardiovascular medicine. It refers to adverse events, usually purely subjective, that result from expectations of harm from a drug, placebo, other therapeutic intervention or a nonmedical situation. These expectations can be driven by many factors including the informed consent form in a clinical trial, warnings about adverse effects communicated by clinicians when prescribing a drug, and information in the media about the dangers of certain treatments. The nocebo effect is the best explanation for the high rate of muscle and other symptoms attributed to statins in observational studies and clinical practice, but not in randomized controlled trials, where muscle symptoms, and rates of discontinuation due to any adverse event, are generally similar in the statin and placebo groups. Statin-intolerant patients usually tolerate statins under double-blind conditions, indicating that the intolerance has little if any pharmacological basis. Known techniques for minimizing the nocebo effect can be applied to the prevention and management of statin intolerance. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  12. The efficiency of cardiovascular risk assessment: do the right patients get statin treatment?

    Science.gov (United States)

    van Staa, Tjeerd-Pieter; Smeeth, Liam; Ng, Edmond S-W; Goldacre, Ben; Gulliford, Martin

    2013-01-01

    Objective To evaluate targeting of statin prescribing for primary prevention to those with high cardiovascular disease (CVD) risk. Design Two cohort studies including the general population and initiators of statins aged 35–74 years. Setting UK primary care records in the Clinical Practice Research Datalink. Patients 3.8 million general population patients and 300 914 statin users. Intervention Statin prescribing. Main outcome measures Statin prescribing by CVD risk; observed 5-year CVD risks; variability between practices. Results Statin prescribing increased substantially over time to patients with high 10-year CVD risk (≥20%): 7.0% of these received a statin prior to 2007, and 30.4% in 2007 onwards. Prescribing to patients with low risk (<15%) also increased (from 1.9% to 5.0%). Only about half the patients initiating statin treatment were high risk according to CVD risk score. The 5-year CVD risks, as observed during statin treatment, reduced over calendar time (from 17.0% to 7.1%). There was a large variation between general practices in the percentage of high-risk patients prescribed a statin in 2007 onwards, ranging from 8.2% to 61.5%. For low-risk patients, these varied from 2.1% to 29.1%. Conclusions There appeared to be substantive overuse in low CVD risk and underuse in high CVD risk (600 000 and 850 000 patients, respectively, in the UK since 2007). There is wide variation between practices in statin prescribing to patients at high CVD risk. There is a clear need for randomised trials for the best strategy to target statin treatment and manage CVD risk for primary prevention. PMID:23735939

  13. Statin-associated memory loss: analysis of 60 case reports and review of the literature.

    Science.gov (United States)

    Wagstaff, Leslie R; Mitton, Melinda W; Arvik, Beth McLendon; Doraiswamy, P Murali

    2003-07-01

    To review case reports of statin-associated memory loss as well as the available published evidence for and against such a link. We searched the MedWatch drug surveillance system of the Food and Drug Administration (FDA) from November 1997-February 2002 for reports of statin-associated memory loss. We also reviewed the published literature (using MEDLINE) and prescribing information for these drugs. Of the 60 patients identified who had memory loss associated with statins, 36 received simvastatin, 23 atorvastatin, and 1 pravastatin. About 50% of the patients noted cognitive adverse effects within 2 months of therapy. Fourteen (56%) of 25 patients noted improvement when the statin was discontinued. Memory loss recurred in four patients who were rechallenged with the drug. None of the 60 reported cognitive test results. Two placebo-controlled trials found no benefits for statins on cognition or disability. One randomized controlled trial of simvastatin found no effects on cerebrospinal amyloid levels. In one small, randomized study, patients receiving statins showed a trend toward lower cognitive performance than those receiving placebo. Five observational studies found a lower risk of dementia among patients receiving statins. Current literature is conflicting with regard to the effects of statins on memory loss. Experimental studies support links between cholesterol intake and amyloid synthesis; observational studies indicate that patients receiving statins have a reduced risk of dementia. However, available prospective studies show no cognitive or antiamyloid benefits for any statin. In addition, case reports raise the possibility that statins, in rare cases, may be associated with cognitive impairment, though causality is not certain.

  14. LIPID-LOWERING EFFICACY OF ROSUVASTATIN COMPARED WITH OTHER STATINS

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    A. N. Meshkov

    2015-12-01

    Full Text Available Assessment of lipid-lowering effect of rosuvastatin is presented, as well as the main results of the study of rosuvastatin therapy efficacy , in comparison with other statins, received in controlled clinical trials of the GALAXY program: COMETS, LUNAR, MERCURY-I, SOLAR, STELLAR.

  15. LIPID-LOWERING EFFICACY OF ROSUVASTATIN COMPARED WITH OTHER STATINS

    Directory of Open Access Journals (Sweden)

    A. N. Meshkov

    2012-01-01

    Full Text Available Assessment of lipid-lowering effect of rosuvastatin is presented, as well as the main results of the study of rosuvastatin therapy efficacy , in comparison with other statins, received in controlled clinical trials of the GALAXY program: COMETS, LUNAR, MERCURY-I, SOLAR, STELLAR.

  16. Salvia officinalis (Sage) Leaf Extract as Add-on to Statin Therapy in Hypercholesterolemic Type 2 Diabetic Patients: a Randomized Clinical Trial.

    Science.gov (United States)

    Kianbakht, Saeed; Nabati, Farzaneh; Abasi, Behrooz

    2016-01-01

    The efficacy and safety of Salvia officinalis combined with statin have not been evaluated in dyslipidemic diabetes mellitus type 2 (DDMT2) so far. The plant extract antioxidant activity was determined by the DPPH radical scavenging assay. The total flavonoid, total phenolic and quercetin contents of the capsules containing the plant extract were also measured. Moreover, the effects of 2-month extract intake (500 mg capsule three times a day) as add-on to daily use of 15 mg glyburide, 2000 mg metformin and 10 mg atorvastatin on the blood levels of fasting glucose (FG), 2 h postprandial glucose (2hPPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride, high-density lipoprotein cholesterol (HDL-C), serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT), creatinine and body mass index were studied in 50 patients and compared with the placebo group (n=50).The extract IC 50 in the DPPH assay was 87.26±0.003 µg/mL (mean±SD), whereas the ascorbic acid IC 50 was 5.626± 0.001 µg/mL (mean±SD). The total flavonoid, total phenolic and quercetin contents of the capsule containing the plant extract were 39.76±3.58 mg of rutin equivalents (mean±SD), 30.33±1.23 mg of gallic acid (mean±SD) and 0.13 mg, respectively. The extract lowered FG, 2hPPG, HbA1c, TC, LDL-C and triglyceride levels, but increased HDL-C level compared to the placebo at the endpoint (P<0.05). The extract did not affect the other parameters significantly and no adverse effect was reported. The extract has substantial antioxidant activity which may be beneficial for the prevention of the cardiovascular complications of DDMT2. Moreover, addition of the extract to statin therapy is apparently safe and further improves lipid profile.

  17. Effect of statin use on outcomes of adults with candidemia.

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    Guillermo Cuervo

    Full Text Available 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=<.001 and prior 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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

    2013-01-01

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

  20. Statin Resistance and Export

    DEFF Research Database (Denmark)

    Ley, Ana

    . and Aspergillus sp.. Production limitations associated with the unique physiology and morphology of the natural producers can be overcome by heterologous expression of the pathway in a fast-growing host, such as S. cerevisiae. Future construction of S. cerevisiae cell factory for the production of high.......25 mM to at least 1.24 mM. Successful complementation of Sc-HMG1 and Sc-HMG2 in yeast, in addition, proved that MlcD functions as HMGCR. A phylogenetic analysis of fungal HMGCRs revealed that HMGCRs from the known statin gene clusters (mlcD and lvrA/mokG) are likely derived from HMGCRs involved...

  1. An assessment by the Statin Diabetes Safety Task Force: 2014 update.

    Science.gov (United States)

    Maki, Kevin C; Ridker, Paul M; Brown, W Virgil; Grundy, Scott M; Sattar, Naveed; The Diabetes Subpanel of the National Lipid Association Expert Panel

    2014-01-01

    Statin therapy reduces the risk of myocardial infarction, stroke, and cardiovascular death by 25% to 30% in primary as well as secondary prevention patients. Thus, statins are the pharmacologic therapy of choice for the management of high blood cholesterol levels. Prompted by examination of clinical trial data suggesting a modest, but statistically significant, increase in the incidence of new-onset type 2 diabetes mellitus with statin use, the US Food and Drug Administration in 2012 added a statement to the labels of statin medications indicating that increases in glycated hemoglobin (HbA1C) and fasting glucose levels have been reported with statin use. This labeling change has raised questions among clinicians regarding the relative benefits and risks of statin use, both among patients with diabetes mellitus and among those with diabetes risk factors. This 2014 report from the Diabetes Subpanel of the National Lipid Association Expert Panel on Statin Safety reviews the published evidence relating statin use to the hazard for diabetes mellitus or worsening glycemia, examines potential mechanisms that may mediate the relationship between statin use and diabetes mellitus risk, and suggests future research efforts. Given the well-established benefits of statin therapy in the primary and secondary prevention of cardiovascular events among those with indications for treatment, no changes to clinical practice are recommended other than the measurement of HbA1C or fasting glucose in those deemed to also be at elevated diabetes risk after initiating statin therapy, and potentially before initiation in selected patients considered to be at elevated risk of developing diabetes. The panel advocates following recommendations from the American Diabetes Association, or other relevant guidelines if outside the United States, for screening and diagnosis as well as lifestyle modification for prevention or delay of diabetes mellitus in those with prediabetes or other risk factors

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

    Science.gov (United States)

    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.

  3. Statins and memory loss: An Australian experience.

    Science.gov (United States)

    Jamolowicz, Anna I; Chen, Huei-Yang; Panegyres, Peter K

    2015-01-01

    Statins are a first-line drug treatment for hypercholesterolaemia. Recently there has been general public and media interest surrounding uses and side effects of statins, including memory loss. We analysed an Australian experience in statin usage in an attempt to improve understanding of the relationship between statins and memory-related adverse events. Total adverse events (TAE) and adverse events with single suspected medicines (SSM) for memory loss and other memory-related adverse events were searched for statin compounds from January 1992 to May 2013, using the Medicare Australia and Pharmaceutical Benefits Scheme (PBS) websites and Therapeutic Goods Administration (TGA) adverse events data. TAE and SSM were compared to the number of prescriptions by item number searched using the PBS. The process was repeated for non-statin cholesterol-lowering drugs. The most common adverse event was amnesia (167 events for statins and six for non-statins). There were 239 TAE (incidence rate=0.88) listed for statins and 10 for non-statins (incidence rate=0.53). There were 217 SSM events listed for the statins (incidence rate = 0.08) and eight for the alternatives (incident rate=0.04). The differences between TAE and SSM incidence rates between statins and non-statins drugs were not significant (both p values >0.05). We found that there were no differences in memory-related adverse events between statins and other cholesterol-lowering medications using Australian PBS and TGA adverse events data.

  4. Excess sudden cardiac deaths after short-term clarithromycin administration in the CLARICOR trial: why is this so, and why are statins protective?

    DEFF Research Database (Denmark)

    Winkel, Per; Hilden, Jørgen; Fischer Hansen, Jørgen

    2011-01-01

    To elucidate potential mechanisms for the clarithromycin-induced excess mortality observed in the CLARICOR trial during 2.6 year follow-up of patients with stable coronary artery disease.......To elucidate potential mechanisms for the clarithromycin-induced excess mortality observed in the CLARICOR trial during 2.6 year follow-up of patients with stable coronary artery disease....

  5. Total cardiovascular disease burden: comparing intensive with moderate statin therapy insights from the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial

    DEFF Research Database (Denmark)

    Tikkanen, Matti J; Szarek, Michael; Fayyad, Rana

    2009-01-01

    , using the Wei, Lin, and Weissfeld method. BACKGROUND: Time-to-first-event analysis of data is frequently utilized to provide efficacy outcome information in coronary heart disease prevention trials. However, during the course of such long-term trials, a large number of events occur subsequent...

  6. Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)

    DEFF Research Database (Denmark)

    Holme, Ingar; Strandberg, Timo E; Faergeman, Ole

    2009-01-01

    BACKGROUND: Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). AIMS: To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial...... with the occurrence of new-onset HF. Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non......-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information...

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

    Science.gov (United States)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    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. Findings For 17802 patients in the JUPITER trial...

  9. False Positive STEMI Activations in a Regional Network: Comprehensive Analysis and Clinical Impact. Results From the Catalonian Codi Infart Network.

    Science.gov (United States)

    Regueiro, Ander; Fernández-Rodríguez, Diego; Freixa, Xavier; Bosch, Xavier; Martín-Yuste, Victoria; Brugaletta, Salvatore; Roqué, Mercè; Sabaté, Manel; Masotti, Mónica

    2017-07-12

    ST-segment elevation myocardial infarction (STEMI) network activation by a noncardiologist reduces delay times but may increase the rate of false-positive STEMI diagnoses. We aimed to determine the prevalence, predictors, and clinical impact of false-positive activations within the Catalonian STEMI network (Codi Infart). From January 2010 through December 2011, all consecutive patients treated within the Codi Infart network were included. Code activations were classified as appropriate if they satisfied both electrocardiogram and clinical STEMI criteria. Appropriate activations were classified as false positives using 2 nonexclusive definitions: a) "angiographic" if a culprit coronary artery was not identified, and b) "clinical" if the discharge diagnosis was other than STEMI. In total, 5701 activations were included. Appropriate activation was performed in 87.8% of the episodes. The rate of angiographic false positives was 14.6%, while the rate of clinical false positives was 11.6%. Irrespective of the definition, female sex, left bundle branch block, and previous myocardial infarction were independent predictors of false-positive STEMI diagnoses. Using the clinical definition, hospitals without percutaneous coronary intervention and patients with complications during the first medical contact also had a false-positive STEMI diagnoses rate higher than the mean. In-hospital and 30-day mortality rates were similar for false-positive and true-positive STEMI patients after adjustment for possible confounders. False-positive STEMI diagnoses were frequent. Outcomes were similar for patients with a true-positive or false-positive STEMI diagnosis treated within a STEMI network. The presence of any modifiable predictors of a false-positive STEMI diagnosis warrants careful assessment to optimize the use of STEMI networks. Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Statin precipitated lactic acidosis?

    Science.gov (United States)

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

    2004-09-01

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

  11. Statin Use and Breast Cancer Survival: A Nationwide Cohort Study from Finland

    Science.gov (United States)

    Murtola, Teemu J.; Visvanathan, Kala; Artama, Miia; Vainio, Harri; Pukkala, Eero

    2014-01-01

    Recent studies have suggested that statins, an established drug group in the prevention of cardiovascular mortality, could delay or prevent breast cancer recurrence but the effect on disease-specific mortality remains unclear. We evaluated risk of breast cancer death among statin users in a population-based cohort of breast cancer patients. The study cohort included all newly diagnosed breast cancer patients in Finland during 1995–2003 (31,236 cases), identified from the Finnish Cancer Registry. Information on statin use before and after the diagnosis was obtained from a national prescription database. We used the Cox proportional hazards regression method to estimate mortality among statin users with statin use as time-dependent variable. A total of 4,151 participants had used statins. During the median follow-up of 3.25 years after the diagnosis (range 0.08–9.0 years) 6,011 participants died, of which 3,619 (60.2%) was due to breast cancer. After adjustment for age, tumor characteristics, and treatment selection, both post-diagnostic and pre-diagnostic statin use were associated with lowered risk of breast cancer death (HR 0.46, 95% CI 0.38–0.55 and HR 0.54, 95% CI 0.44–0.67, respectively). The risk decrease by post-diagnostic statin use was likely affected by healthy adherer bias; that is, the greater likelihood of dying cancer patients to discontinue statin use as the association was not clearly dose-dependent and observed already at low-dose/short-term use. The dose- and time-dependence of the survival benefit among pre-diagnostic statin users suggests a possible causal effect that should be evaluated further in a clinical trial testing statins’ effect on survival in breast cancer patients. PMID:25329299

  12. Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality

    DEFF Research Database (Denmark)

    Nielsen, Sune Fallgaard; Nordestgaard, Børge Grønne

    2016-01-01

    AIM: We tested the hypothesis that statin-related news stories, cardiovascular disease, diabetes, statin dose, calendar year, and socio-demographic status are associated with early statin discontinuation. We also examined frequency and consequences of early statin discontinuation. METHODS...... AND RESULTS: From the entire Danish population, we studied 674 900 individuals aged 40 or older who were initiated on statin therapy in 1995-2010, and followed them until 31 December 2011. Individuals on statins increased from statin discontinuation increased from 6......% in 1995 to 18% in 2010. The odds ratios for early statin discontinuation vs. continued use were 1.09 (95% confidence interval, 1.06-1.12) for negative statin-related news stories, 1.04 (1.02-1.07) per increasing calendar year, 1.04 (1.02-1.06) per increasing defined daily dose of statin, 1.05 (1...

  13. Anti inflammatory effects of statin in COPD

    OpenAIRE

    Nasef Abdelsalam Rezk; Ahmad Elewa

    2013-01-01

    Introduction: Statins are now becoming recognized as powerful antiinflammatory agents that exert beneficial effects beyond low-density lipoprotein cholesterol reduction [1]. COPD patients receiving statins obtain a benefit from these therapeutic agents. Clearly, the best medical evidence for the association of statins with improved outcomes for COPD patients [2]. We aimed in this study to assess anti inflammatory effects of statin in COPD patients. Patients and methods: We studied 28...

  14. Use of statins and risk of glioma

    DEFF Research Database (Denmark)

    Gaist, David; Andersen, L; Hallas, Jesper

    2013-01-01

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

  15. Statin intolerance: more questions than answers.

    Science.gov (United States)

    Guyton, John R; Campbell, Kristen B; Lakey, Wanda C

    2014-01-01

    The dramatic effectiveness of statins in improving the course of atherosclerotic cardiovascular disease tends to overshadow questions of statin intolerance. Thus after more than 25 years of clinical statin use, intolerance remains a poorly understood, frustrating issue for patients and providers. It has been extraordinarily difficult to define statin intolerance and its implications for clinical practice. Here, we briefly summarize current knowledge and raise questions that need to be addressed.

  16. Statins for the primary prevention of cardiovascular disease

    Science.gov (United States)

    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

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

    DEFF Research Database (Denmark)

    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.......0003; statin-clarithromycin interaction P = 0.0029) and all-cause mortality (HR, 1.33; 95% CI, 1.05-1.67; P = 0.016; statin-clarithromycin interaction P = 0.41). Multivariate analysis and 6-year follow up confirmed these results. Concomitant statin treatment in stable patients with coronary heart disease...

  18. 2013 consensus statement for early reperfusion and pharmaco-invasive approach in patients presenting with chest pain diagnosed as STEMI (ST elevation myocardial infarction) in an Indian setting.

    Science.gov (United States)

    Dalal, J J; Alexander, T; Banerjee, P S; Dayasagar, V; lyengar, S S; Kerkar, P G; Mullasari, A; Sathe, S P; Wander, G S

    2014-06-01

    patients with symptom duration India. It must be recognized that even when randomized clinical trials have been undertaken, treatment options may be limited by resources. The Cardiocare STEMI experts realize that the recommended diagnostic examinations and treatment options may not be available or affordable in all parts of India. Cost-effectiveness is becoming an increasingly important issue when deciding upon therapeutic strategies. As always with guidelines/consensus statement, they are not prescriptive. Clinical scenario and patients vary so much from one another that individual care is paramount, and there is still an important place for clinical judgment, experience, and common sense. The mandate of the Cardiocare STEMI expert consensus is to recommend evidence-based standards of care, related targets and strategies for implementation of standards in the management of STEMI. CONTEXT AND USE: This document should be taken as consensus recommendations by qualified experts, not as rigid rules. It comprises of published evidence and may not cover every eventuality; new evidence is published every day. Furthermore, this should not be used as a legal resource, as the general nature cannot provide individualized guidance for all patients under all clinical circumstances.

  19. Effects of statin therapy according to plasma high-sensitivity C-reactive protein concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): a retrospective analysis

    DEFF Research Database (Denmark)

    McMurray, John J V; Kjekshus, John; Gullestad, Lars

    2009-01-01

    -generating study, we found a significant interaction between hs-CRP and the effect of rosuvastatin for most end points whereby rosuvastatin treatment was associated with better outcomes in patients with hs-CRP > or = 2.0 mg/L. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique...

  20. On-Treatment Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, Triglycerides, and Lipid Ratios in Relation to Residual Vascular Risk After Treatment With Potent Statin Therapy JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin)

    NARCIS (Netherlands)

    Mora, Samia; Glynn, Robert J.; Boekholdt, S. Matthijs; Nordestgaard, Børge G.; Kastelein, John J. P.; Ridker, Paul M.

    2012-01-01

    Objectives 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

  1. Statin treatment in multiple sclerosis: a systematic review and meta-analysis.

    Science.gov (United States)

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

    2015-04-01

    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. Our objective was to assess current evidence to support statin treatment in MS and clinically isolated syndrome (CIS). We conducted a systematic literature review of EMBASE, PubMed, and CINAHL databases, clinical trials registries, and unpublished conference meeting abstracts as well as reference lists between 1 and 8 June 2014 and repeated it on 1 December 2014. Randomized controlled trials (RCTs) of statins, in any form or dosage, as monotherapy or add-on to established therapy in relapsing-remitting MS (RRMS), progressive MS, and CIS were included. Data were extracted using pre-defined fields to measure study quality. Meta-analysis was performed with regards to pre-defined outcome measures of relapse activity, magnetic resonance imaging (MRI) activity, Expanded Disability Status Scale (EDSS) progression, and adverse events using a fixed-effects model due to low heterogeneity between studies. Eight trials were included in the review [five of statin add-on to interferon (IFN)-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 to the low number of trials in CIS and SPMS, meta-analysis of primary outcomes was only performed for RRMS studies. Meta-analysis showed no significant effect of statin add-on to IFNβ therapy. Indeed, a trend towards an

  2. Patofysiologiske aspekter ved statiners diabetogene effekt

    DEFF Research Database (Denmark)

    Pilemann-Lyberg, Sascha; Solis, Anette Bratt; Gæde, Peter

    2014-01-01

    Statins are potent inhibitors of cholesterol biosynthesis. Statins are beneficial in the primary and secondary prevention of coronary heart disease. Recent studies indicate that there is an association between statin use and the development of new-onset diabetes mellitus. This article reviews the...

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

    Science.gov (United States)

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

    2015-12-01

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

  4. Impact of statin therapy on all-cause mortality and ICD interventions in heart failure patients - a systematic review.

    Science.gov (United States)

    Bazoukis, George; Papadatos, Stamatis S; Letsas, Konstantinos P; Pagkalidou, Eirini; Korantzopoulos, Panagiotis

    2017-10-01

    Implantable cardioverter defibrillators (ICDs) have a unique role for the primary and secondary prevention of sudden cardiac death (SCD). The aim of our systematic review is to present the existing data about the impact of statins on all-cause mortality and ICD interventions in heart failure (HF) patients who had an ICD implanted either for primary or for secondary prevention of SCD. We searched PubMed database and the reference list of the relevant studies for retrieving studies evaluating the effect of statins on all-cause mortality and ICD interventions in HF patients. We finally included 17 relevant studies in our systematic review. Of them, nine studies included data about the impact of statins on all-cause mortality, eight studies about the impact of statins on appropriate ICD interventions and three studies about the impact of statins on inappropriate ICD interventions in HF patients. These data showed that statins seem to have a beneficial role in the reduction of all-cause mortality and ICD interventions in HF patients. Statins seem to have a beneficial role in the reduction of all-cause mortality and ICD interventions in HF patients. However, further research about pleiotropic effects of statins is needed as well randomized control trials to elucidate the exact role of statin therapy in ICD outcomes.

  5. Key interventions and quality indicators for quality improvement of STEMI care: a RAND Delphi survey.

    Science.gov (United States)

    Aeyels, Daan; Sinnaeve, Peter R; Claeys, Marc J; Gevaert, Sofie; Schoors, Danny; Sermeus, Walter; Panella, Massimiliano; Coeckelberghs, Ellen; Bruyneel, Luk; Vanhaecht, Kris

    2017-12-13

    Identification, selection and validation of key interventions and quality indicators for improvement of in hospital quality of care for ST-elevated myocardial infarction (STEMI) patients. A structured literature review was followed by a RAND Delphi Survey. A purposively selected multidisciplinary expert panel of cardiologists, nurse managers and quality managers selected and validated key interventions and quality indicators prior for quality improvement for STEMI. First, 34 experts (76% response rate) individually assessed the appropriateness of items to quality improvement on a nine point Likert scale. Twenty-seven key interventions, 16 quality indicators at patient level and 27 quality indicators at STEMI care programme level were selected. Eighteen additional items were suggested. Experts received personal feedback, benchmarking their score with group results (response rate, mean, median and content validity index). Consequently, 32 experts (71% response rate) openly discussed items with an item-content validity index above 75%. By consensus, the expert panel validated a final set of 25 key interventions, 13 quality indicators at patient level and 20 quality indicators at care programme level prior for improvement of in hospital care for STEMI. A structured literature review and multidisciplinary expertise was combined to validate a set of key interventions and quality indicators prior for improvement of care for STEMI. The results allow researchers and hospital staff to evaluate and support quality improvement interventions in a large cohort within the context of a health care system.

  6. Time-to-reperfusion in STEMI undergoing interhospital transfer using smartphone and WhatsApp messenger.

    Science.gov (United States)

    Astarcioglu, Mehmet Ali; Sen, Taner; Kilit, Celal; Durmus, Halil Ibrahim; Gozubuyuk, Gokhan; Kalcik, Macit; Karakoyun, Suleyman; Yesin, Mahmut; Zencirkiran Agus, Hicaz; Amasyali, Basri

    2015-10-01

    The objective of this study is to assess the efficacy of WhatsApp application as a communication method among the emergency physician (EP) in a rural hospital without percutaneous coronary intervention (PCI) capability and the interventional cardiologist at a tertiary PCI center. Current guidelines recommend that patients with ST-segment elevation myocardial infarction (STEMI) receive primary PCI within 90 minutes. This door-to-balloon (D2B) time has been difficult to achieve in rural STEMI. We evaluated 108 patients with STEMI in a rural hospital with emergency department but without PCI capability to determine the impact of WhatsApp triage and activation of the cardiac catheterization laboratory on D2B time. The images were obtained from cases of suspected STEMI using the smartphones by the EP and were sent to the interventional cardiologist via the WhatsApp application (group 1, n=53). The control group included concurrently treated patients with STEMI during the same period but not receiving triage (group 2, n=55). The D2B time was significantly shorter in the intervention group (109±31 vs 130±46 minutes, PWhatsApp triage with activation of the cardiac catheterization laboratory was associated with shorter D2B time and results in a greater proportion of patients achieving guideline recommendations. The method is cheap, quick, and easy to operate. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2014-11-01

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

  8. Statins Determination: A Review of Electrochemical Techniques.

    Science.gov (United States)

    Antal, I; Koneracka, M; Zavisova, V; Kubovcikova, M; Kormosh, Zh; Kopcansky, P

    2017-11-02

    The use of electroanalytical techniques for the determination of statins (Atorvastatin, Fluvastatin, Lovastatin, Pitavastatin, Pravastatin, Rosuvastatin and Simvastatin) is reviewed covering the period from 1997 to 2016. Among all of the published electrochemical methods, voltammetry and polarography are the most popular techniques for the determination of statins, and both are used for the analysis of pharmaceutical dosage forms and biological samples. The determination of statins by a potentiometric method using ion-selective electrodes is reported in only few papers. Сoulometry and conductometry have been not used for the determination of statins till date. Current trends in developing new electrochemical methods for the analysis of statins are discussed.

  9. Statin use and survival following glioblastoma multiforme

    DEFF Research Database (Denmark)

    Gaist, David; Hallas, Jesper; Friis, Søren

    2014-01-01

    AIM: While some studies indicate a potential chemopreventive effect of statin use on the risk of glioma, the effect of statins on the prognosis of brain tumours has not yet been examined. We thus conducted a cohort study evaluating the influence of statin use on survival in patients...... 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...... redeemed prescriptions) was matched to two statin non-users (

  10. Statin-associated myopathy: from genetic predisposition to clinical management.

    Science.gov (United States)

    Vrablik, M; Zlatohlavek, L; Stulc, T; Adamkova, V; Prusikova, M; Schwarzova, L; Hubacek, J A; Ceska, R

    2014-01-01

    Statin-associated myopathy (SAM) represents a broad spectrum of disorders from insignificant myalgia to fatal rhabdomyolysis. Its frequency ranges from 1-5 % in clinical trials to 15-20 % in everyday clinical practice. To a large extent, these variations can be explained by the definition used. Thus, we propose a scoring system to classify statin-induced myopathy according to clinical and biochemical criteria as 1) possible, 2) probable or 3) definite. The etiology of this disorder remains poorly understood. Most probably, an underlying genetic cause is necessary for overt SAM to develop. Variants in a few gene groups that encode proteins involved in: i) statin metabolism and distribution (e.g. membrane transporters and enzymes; OATP1B1, ABCA1, MRP, CYP3A4), ii) coenzyme Q10 production (e.g. COQ10A and B), iii) energy metabolism of muscle tissue (e.g. PYGM, GAA, CPT2) and several others have been proposed as candidates which can predispose to SAM. Pharmacological properties of individual statin molecules (e.g. lipophilicity, excretion pathways) and patients´ characteristics influence the likelihood of SAM development. This review summarizes current data as well as our own results.

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

    LENUS (Irish Health Repository)

    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.

  12. Combination of Thrombolysis and Statins in Acute Stroke Is Safe: Results of the STARS Randomized Trial (Stroke Treatment With Acute Reperfusion and Simvastatin).

    Science.gov (United States)

    Montaner, Joan; Bustamante, Alejandro; García-Matas, Silvia; Martínez-Zabaleta, Maite; Jiménez, Carmen; de la Torre, Javier; Rubio, Francisco R; Segura, Tomás; Masjuán, Jaime; Cánovas, David; Freijo, Mar; Delgado-Mederos, Raquel; Tejada, Javier; Lago, Aida; Bravo, Yolanda; Corbeto, Natália; Giralt, Dolors; Vives-Pastor, Bárbara; de Arce, Anna; Moniche, Francisco; Delgado, Pilar; Ribó, Marc

    2016-11-01

    The STARS trial (Stroke Treatment With Acute Reperfusion and Simvastatin) was conducted to demonstrate the efficacy and safety of simvastatin treatment in acute stroke. STARS07 was a multicentre, phase IV, prospective, randomized, double-blind, placebo-controlled trial. Patients with Acute ischemic stroke recruited within 12 hours from symptom onset were randomized to oral simvastatin 40 mg or placebo, once daily for 90 days. Primary outcome was proportion of independent patients (modified Rankin Scale score of ≤2) at 90 days. Safety end points were hemorrhagic transformation, hemorrhagic events, death, infections, and serious adverse events. From April 2009 to March 2014, 104 patients were included. Fifty-five patients received intravenous tissue-type plasminogen activator. No differences were found between treatment arms regarding the primary outcome (adjusted odds ratio, 0.99 [0.35-2.78]; P=0.98). Concerning safety, no significant differences were found in the rate of hemorrhagic transformation of any type, nor symptomatic hemorrhagic transformation. There were no differences in other predefined safety outcomes. In post hoc analyses, for patients receiving tissue-type plasminogen activator, a favorable effect for simvastatin treatment was noted with higher proportion of patients experiencing major neurological recovery (adjusted odds ratio, 4.14 [1.18-14.4]; P=0.02). Simvastatin plus tissue-type plasminogen activator combination seems safe in acute stroke, with low rates of bleeding complications. Because of the low recruitment, the STARS trial was underpowered to detect differences in simvastatin efficacy. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01073007. © 2016 American Heart Association, Inc.

  13. Comparison of plaque characteristics in narrowings with ST-elevation myocardial infarction (STEMI), non-STEMI/unstable angina pectoris and stable coronary artery disease (from the ADAPT-DES IVUS Substudy).

    Science.gov (United States)

    Dong, Liang; Mintz, Gary S; Witzenbichler, Bernhard; Metzger, D Christopher; Rinaldi, Michael J; Duffy, Peter L; Weisz, Giora; Stuckey, Thomas D; Brodie, Bruce R; Yun, Kyeong Ho; Xu, Ke; Kirtane, Ajay J; Stone, Gregg W; Maehara, Akiko

    2015-04-01

    Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) was a prospective, multicenter registry of 8,582 consecutive stable and unstable patients who underwent percutaneous coronary intervention using a drug-eluting stent. We sought to identify key morphologic features leading to ST-segment elevation myocardial infarction (STEMI) versus non-STEMI (NSTEMI) or unstable angina pectoris (UA) versus stable coronary artery disease (CAD) presentation. In the prespecified grayscale and virtual histology (VH) substudy of ADAPT-DES, preintervention imaging identified 676 patients with a single culprit lesion. The relation between lesion morphology and clinical presentation was compared among patients with (1) STEMI, (2) NSTEMI or UA, and (3) stable CAD. Intravascular ultrasound identified more plaque rupture and VH thin-cap fibroatheroma (TCFA) in STEMI lesions compared with NSTEMI/UA or stable CAD lesions; conversely, fibroatheromas appeared more often calcified with a thick fibrous cap in stable CAD. Minimum lumen cross-sectional area (MLA) was smaller with larger plaque burden and positive remodeling in STEMI lesions. Lesions with plaque rupture versus those without plaque rupture showed higher prevalence of VH-TCFA and larger plaque burden with positive remodeling, especially in patients with STEMI. Multivariate analysis showed that in the lesions with plaque rupture, plaque burden at the MLA site was the only independent predictor for STEMI (cutoff of plaque burden = 85%) and in lesions without plaque rupture, MLA was the only independent predictor for STEMI (cutoff of MLA = 2.3 mm(2)). In conclusion, culprit lesions causing STEMI have smaller lumen areas, greater plaque burden, and more plaque rupture or VH-TCFA compared with NSTEMI/UA or stable CAD; in lesions with plaque rupture, only plaque burden predicted STEMI, and in lesions without plaque rupture, only MLA area predicted STEMI. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Does Googling lead to statin intolerance?

    Science.gov (United States)

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

    2018-07-01

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

  15. Statin use and risk for ovarian cancer

    DEFF Research Database (Denmark)

    Baandrup, L; Dehlendorff, C; Friis, Søren

    2015-01-01

    BACKGROUND: Limited data suggest that statin use reduces the risk for ovarian cancer. METHODS: Using Danish nationwide registries, we identified 4103 cases of epithelial ovarian cancer during 2000-2011 and age-matched them to 58,706 risk-set sampled controls. Conditional logistic regression...... was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for epithelial ovarian cancer overall, and for histological types, associated with statin use. RESULTS: We observed a neutral association between ever use of statins and epithelial ovarian cancer risk (OR=0.98, 95% CI=0.......87-1.10), and no apparent risk variation according to duration, intensity or type of statin use. Decreased ORs associated with statin use were seen for mucinous ovarian cancer (ever statin use: OR=0.63, 95% CI=0.39-1.00). CONCLUSIONS: Statin use was not associated with overall risk for epithelial ovarian cancer...

  16. Association between QRS duration on prehospital ECG and mortality in patients with suspected STEMI

    DEFF Research Database (Denmark)

    Hansen, Rikke; Frydland, Martin; Møller-Helgestad, Ole Kristian

    2017-01-01

    BACKGROUND: QRS duration has previously shown association with mortality in patients with acute myocardial infarction treated with thrombolytics, less is known in patients with suspected ST segment elevation myocardial infarction (STEMI) when assessing QRS duration on prehospital ECG. Thus......, the objective was to investigate the prognostic effect of QRS duration on prehospital ECG and presence of classic left and right bundle branch block (LBBB/RBBB) for all-cause mortality in patients with suspected STEMI. METHOD: In total 2105 consecutive patients (mean age 64±13years, 72% men) with suspected...... STEMI were prospectively included. QRS duration was registered from automated QRS measurement on prehospital ECG and patients were divided according to quartiles of QRS duration (111ms). Primary endpoint was all-cause 30-day mortality. Predictors of all-cause mortality were...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Alzheimer's disease, cholesterol, and statins: the junctions of important metabolic pathways.

    Science.gov (United States)

    Silva, Tiago; Teixeira, José; Remião, Fernando; Borges, Fernanda

    2013-01-21

    Recent years have seen a significant increase in published data supporting the positive effects of statins on neurodegenerative diseases, in particular on Alzheimer's disease. Statins show neuroprotective activity by a combination of different cellular and systemic mechanisms that are based on the inhibition of the biosynthesis of cholesterol and isoprenoid by-products. The promising results obtained in vivo and in epidemiological studies are generally not in accordance with those of placebo-controlled randomized clinical trials. Nevertheless, these results make statins valuable assets for disease prevention rather than therapeutic agents for use when disease symptoms are already displayed. Thus, the modulation of midlife cholesterol and/or statin administration prior to the appearance of dementia or cognitive impairment may have a better long-term outcome. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Antiplatelet therapy in STEMI undergoing primary PCI, when, which one and how long.

    Science.gov (United States)

    Baralis, Giorgio; Rossini, Roberta; Musumeci, Giuseppe

    2018-02-19

    Reperfusion therapy for patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) involves primary percutaneous coronary intervention (PPCI) and concomitant dual antiplatelet therapy (DAPT) with combination of a P2Y12 inhibitor and acetylsalicylic acid (ASA). Decision regarding DAPT can be challenging clinically in the modern era with the evolution of newer stents, more potent antiplatelet agents and novel anticoagulant drugs in addition to an older patient population with multiple comorbidities. This review outlines the currently available antiplatelet treatments, and their place within the therapeutic timeline of a patient presenting with STEMI.

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

    Science.gov (United States)

    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; ...

  1. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

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

  2. Statin intolerance - a question of definition.

    Science.gov (United States)

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

    2017-01-01

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

  3. RHOA is a modulator of the cholesterol-lowering effects of statin.

    Science.gov (United States)

    Medina, Marisa W; Theusch, Elizabeth; Naidoo, Devesh; Bauzon, Frederick; Stevens, Kristen; Mangravite, Lara M; Kuang, Yu-Lin; Krauss, Ronald M

    2012-01-01

    Although statin drugs are generally efficacious for lowering plasma LDL-cholesterol levels, there is considerable variability in response. To identify candidate genes that may contribute to this variation, we used an unbiased genome-wide filter approach that was applied to 10,149 genes expressed in immortalized lymphoblastoid cell lines (LCLs) derived from 480 participants of the Cholesterol and Pharmacogenomics (CAP) clinical trial of simvastatin. The criteria for identification of candidates included genes whose statin-induced changes in expression were correlated with change in expression of HMGCR, a key regulator of cellular cholesterol metabolism and the target of statin inhibition. This analysis yielded 45 genes, from which RHOA was selected for follow-up because it has been found to participate in mediating the pleiotropic but not the lipid-lowering effects of statin treatment. RHOA knock-down in hepatoma cell lines reduced HMGCR, LDLR, and SREBF2 mRNA expression and increased intracellular cholesterol ester content as well as apolipoprotein B (APOB) concentrations in the conditioned media. Furthermore, inter-individual variation in statin-induced RHOA mRNA expression measured in vitro in CAP LCLs was correlated with the changes in plasma total cholesterol, LDL-cholesterol, and APOB induced by simvastatin treatment (40 mg/d for 6 wk) of the individuals from whom these cell lines were derived. Moreover, the minor allele of rs11716445, a SNP located in a novel cryptic RHOA exon, dramatically increased inclusion of the exon in RHOA transcripts during splicing and was associated with a smaller LDL-cholesterol reduction in response to statin treatment in 1,886 participants from the CAP and Pravastatin Inflamation and CRP Evaluation (PRINCE; pravastatin 40 mg/d) statin clinical trials. Thus, an unbiased filter approach based on transcriptome-wide profiling identified RHOA as a gene contributing to variation in LDL-cholesterol response to statin, illustrating the

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

    Science.gov (United States)

    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

  5. Statins and clinical outcome of acute ischemic stroke: a systematic review

    Directory of Open Access Journals (Sweden)

    Lakhan Shaheen E

    2010-09-01

    Full Text Available Abstract Background Statin therapy is considered an effective measure for the prevention of ischemic stroke. Several recent studies have indicated that treatment with statins, prior to the onset of acute ischemic stroke, may also substantially reduce the severity of stroke and the degree of patient disability. The purpose of the present review is to systematically evaluate the effectiveness of statin pretreatment on functional outcome of acute ischemic stroke and to assess potential adverse events associated with statin use. Methods Relevant articles on the role of statins in acute ischemic stroke were identified via MEDLINE/PubMed, EMBASE, CENTRAL, and by manual searches of the references of identified papers. Clinical studies (most were prospective cohort studies assessing statin therapy for acute ischemic stroke were selected for the review. Only two randomized controlled clinical trials met the criteria to be included in the analysis. Clinical outcome was assessed based on the degree of disability determined with the modified Rankin Scale (mRS and Barthel index (BI. The National Institutes of Health Stroke Scale (NIHSS was used to measure stroke severity. Recurrence of stroke in patients who had suffered from a previous stroke was analyzed with and without statin therapy. Incidence and severity of adverse reactions was reviewed. Because there were too many differences in study outcome measures, a quantitative analysis of data was deemed inappropriate. A qualitative summary of the data was consequently completed. Results Thirteen reports were systematically reviewed to evaluate the efficacy and safety of statins in the pretreatment of acute ischemic stroke. Pretreatment with statins was found to reduce the recurrence of stroke and to result in more favorable outcomes for patients. The beneficial effects of prior statin therapy in acute ischemic stroke were shown to be especially profound in whites, diabetics, elderly patients with

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

    Science.gov (United States)

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

    2016-07-01

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

  7. Primary PCI as the preferred reperfusion therapy in STEMI: it is a matter of time

    DEFF Research Database (Denmark)

    Terkelsen, C J; Christiansen, E H; Sørensen, J T

    2009-01-01

    There is a continuing controversy about the acceptable time-window for primary percutaneous coronary intervention (PPCI) in patients with ST-elevation myocardial infarction (STEMI). Recent American and European guidelines recommend PPCI if the delay in performing PPCI instead of administering...... directly to catheterisation laboratories running 24/7....

  8. Statin intolerance in a referral lipid clinic.

    Science.gov (United States)

    Lakey, Wanda C; Greyshock, Nicole G; Kelley, Carly E; Siddiqui, Mohammad A; Ahmad, Umar; Lokhnygina, Yuliya V; Guyton, John R

    2016-01-01

    Statins effectively prevent atherosclerotic cardiovascular disease, but rates of statin discontinuation after adverse events are high. Describe the range and relative frequencies of adverse events potentially attributable to statins in lipid referral practice and assess statin rechallenge outcomes. Retrospective cohort study of 642 patients with statin-associated adverse events evaluated in a referral lipid clinic between January 1, 2004 and January 27, 2011. Patients experiencing adverse events by organ system included 92% with musculoskeletal, 8% central nervous system, 10% liver, 8% gastrointestinal, 5% peripheral nervous system, 5% skin, and 3% other events. Overlap of organ system involvement occurred in 22.5%. At least 1 follow-up visit was made by 557 patients, among whom overall median follow-up was 25 months. Among patients treated with a statin in the clinic, 71% remained on a statin at the last follow-up visit. Patients with hepatic transaminase increases by history were numerically more likely than the overall group to resume or remain on statin treatment, whereas those reporting central nervous system or gastrointestinal symptoms trended lower for statin maintenance. Among patients who experienced an adverse event after statin rechallenge, the majority (64%) were being treated with intermittent, nondaily dosing at the time of the adverse event. Although musculoskeletal symptoms are reported by 90% of patients with statin intolerance, symptoms involving other organ systems may be more frequent than previously supposed. Understanding the range of symptoms, time course, and impact on daily activities informs counseling in patient-centered practice, but assessment of causation by statins remains challenging. Published by Elsevier Inc.

  9. Pleiotropic and Lipid?lowering Effects of Statins in Hypertension

    OpenAIRE

    Kamberi, Lulzim Selim; Bedri Bakalli, Aurora; Muhamet Budima, Norma; Rashit Gorani, Daut; Karabulut, Ahmet Muzaffer; Talat Pallaska, Kelmend

    2012-01-01

    Background: Data on the lowering effects of statins in hypertensive patients have been mixed and highly controversial. Some studies shows reductions effects of statins in blood pressure, whereas others do not. The evidence in the literature on the effects of statins on blood pressure raises the possibility that statins may directly lower blood pressure in addition to reduce cholesterol levels?pleiotropic effects of statins. Aim of the study: The role of statins as additional treatment in pati...

  10. Statins and transcriptional regulation: The FXR connection

    International Nuclear Information System (INIS)

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

    2005-01-01

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

  11. Statins Decrease Oxidative Stress and ICD Therapies

    Directory of Open Access Journals (Sweden)

    Heather L. Bloom

    2010-01-01

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

  12. Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical outcomes with or without statin therapy: The St Francis Heart Study.

    Science.gov (United States)

    Waheed, Salman; Pollack, Simcha; Roth, Marguerite; Reichek, Nathaniel; Guerci, Alan; Cao, Jie J

    2016-12-01

    The efficacy of statin therapy remains unknown in patients eligible for statin therapy with and without elevated coronary calcium score (CAC). The study sought to evaluate how cardiovascular risk factors, expressed in terms of statin eligibility for primary prevention, and CAC modify clinical outcomes with and without statin therapy. We conducted a post-hoc analysis of the St. Francis Heart Study treatment trial, a double-blind, placebo-controlled randomized controlled trial of atorvastatin (20 mg), vitamin C (1 g), and vitamin E (1000 U) daily, versus placebos in 990 asymptomatic individuals with CAC ≥ 80th percentile for age and gender. Primary cardiovascular outcomes included non-fatal myocardial infarction or coronary death, coronary revascularization, stroke, and peripheral arterial revascularization. We further stratified the treatment and placebo groups by eligibility (eligible when statin indicated) for statin therapy based on 2013 ACC/AHA guidelines and based on CAC categories. After a median follow-up of 4.8 years, cardiovascular events had occurred in 3.9% of the statin treated but not eligible, 4.6% of the untreated and not eligible, 8.9% of the treated and eligible and 13.4% of the untreated and eligible groups, respectively (p300) occurred frequently in more than 35% of the statin not eligible subjects and was associated with a high 10-year event rate (≥17 per 100 person-years). Risk prediction improved significantly when both clinical risk profile and CAC score were combined (net reclassification index p = 0.002). Under the current statin treatment guidelines a small number of statin eligible subjects with low CAC might not benefit from statin therapy within 5 years. However, the statin not eligible subjects with high CAC have high event rate attributing to loss of opportunity for effective primary prevention. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Improving the physician-patient cardiovascular risk dialogue to improve statin adherence

    Directory of Open Access Journals (Sweden)

    Abdolrasulnia Maziar

    2009-06-01

    Full Text Available Abstract Background The purpose of this study was to evaluate the effectiveness of a patient education program developed to facilitate statin adherence. Methods A controlled trial was designed to test the effectiveness of a multifaceted patient education program to facilitate statin adherence. The program included a brief, in-office physician counseling kit followed by patient mailings. The primary end point was adherence to filling statin prescriptions during a 120-day period. Patients new to statins enrolled and completed a survey. Data from a national pharmacy claims database were used to track adherence. Results Patients new to statin therapy exposed to a patient counseling and education program achieved a 12.4 higher average number of statin prescription fill days and were 10% more likely to fill prescriptions for at least 120 days (p = .01. Conclusion Brief in-office counseling on cardiovascular risk followed by patient education mailings can be effective in increasing adherence. Physicians found a one-minute counseling tool and pocket guidelines useful in counseling patients.

  14. [In vitro study over statins effects on cellular growth curves and its reversibility with mevalonate].

    Science.gov (United States)

    Millan Núñez-Cortés, Jesús; Alvarez Rodriguez, Ysmael; Alvarez Novés, Granada; Recarte Garcia-Andrade, Carlos; Alvarez-Sala Walther, Luis

    2014-01-01

    HMG-CoA-Reductase inhibitors, also known as statins, are currently the most powerful cholesterol-lowering drugs available on the market. Clinical trials and experimental evidence suggest that statins have heavy anti-atherosclerotic effects. These are in part consequence of lipid lowering but also result from pleiotropic actions of the drugs. These so-called pleiotropic properties affect various aspects of cell function, inflammation, coagulation, and vasomotor activity. These effects are mediated either indirectly through LDL-c reduction or via a direct effect on cellular functions. Although many of the pleiotropic properties of statins may be a class effect, some may be unique to certain agents and account for differences in their pharmacological activity. So, although statins typically have similar effects on LDL-c levels, differences in chemical structure and pharmacokinetic profile can lead to variations in pleiotropic effects. In this paper we analize the in vitro effects of different statins over different cell lines from cells implicated in atherosclerotic process: endothelial cells, fibroblasts, and vascular muscular cells. In relation with our results we can proof that the effects of different dosis of different statins provides singular effects over growth curves of different cellular lines, a despite of a class-dependent effects. So, pleiotropic effects and its reversibility with mevalonate are different according with the molecule and the dosis. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

  15. Efficacy of Statin Therapy in Inducing Coronary Plaque Regression in Patients with Low Baseline Cholesterol Levels

    Science.gov (United States)

    Nozue, Tsuyoshi; Yamamoto, Shingo; Tohyama, Shinichi; Fukui, Kazuki; Umezawa, Shigeo; Onishi, Yuko; Kunishima, Tomoyuki; Sato, Akira; Miyake, Shogo; Morino, Yoshihiro; Yamauchi, Takao; Muramatsu, Toshiya; Hibi, Kiyoshi; Terashima, Mitsuyasu; Suzuki, Hiroshi; Michishita, Ichiro

    2016-01-01

    Aim: The efficacy of statin therapy in inducing coronary plaque regression may depend on baseline cholesterol levels. We aimed to determine the efficacy of statin therapy in inducing coronary plaque regression in statin-naïve patients with low cholesterol levels using serial intravascular ultrasound (IVUS) data from the treatment with statin on atheroma regression evaluated by virtual histology IVUS (TRUTH) study. Methods: The TRUTH study is a prospective, multicenter trial, comparing the efficacies of pitavastatin and pravastatin in coronary plaque regression in 164 patients. All patients were statin-naïve and received statin therapy only after study enrollment. The primary endpoint was the observation of coronary plaque progression, despite statin therapy. Results: Serial IVUS data, at baseline and after an 8-month follow-up, were available for 119 patients. The patients were divided into three groups based on non-high-density lipoprotein cholesterol (HDL-C) levels—low: ≤ 140 mg/dl, n = 38; moderate: 141–169 mg/dl, n = 42; and high: ≥ 170 mg/dl, n = 39. Coronary plaque progression was noted in the low cholesterol group, whereas plaque regression was noted in the moderate and high cholesterol groups [%Δplaque volume: 2.3 ± 7.4 vs. − 2.7 ± 10.7 vs. − 3.2 ± 7.5, p = 0.004 (analysis of variance)]. After adjusting for all variables, a low non-HDLC level (≤ 140 mg/dl) was identified as an independent predictor of coronary plaque progression [odds ratio, 3.7; 95% confidence interval, 1.5–9.1, p = 0.004]. Conclusion: Serial IVUS data analysis indicated that statin therapy was less effective in inducing coronary plaque regression in patients with low cholesterol levels but more effective in those with high cholesterol levels at baseline. University Hospital Medical Information Network (UMIN) (UMIN ID: C000000311). PMID:27040362

  16. Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance

    DEFF Research Database (Denmark)

    Nissen, Steven E; Stroes, Erik; Dent-Acosta, Ricardo E

    2016-01-01

    IMPORTANCE: Muscle-related statin intolerance is reported by 5% to 20% of patients. OBJECTIVE: To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. DESIGN, SETTING, AND PARTICIPANTS: Two......-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having...... intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01984424....

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

    Science.gov (United States)

    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

  18. STATIN CONTAINING COMPOSITIONS FOR TREATMENT OF CANCER

    NARCIS (Netherlands)

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

    2008-01-01

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

  19. Pleiotropic effects of statins in stroke prevention

    Directory of Open Access Journals (Sweden)

    Yenny

    2009-08-01

    Full Text Available Cardiovascular disease is the leading cause of death and disability, and contributes substantially to healthcare budgets. The lipid-lowering drugs, 3-hydroxy-3-methylgulutaryl-coenzyme A (HMG-CoA reductase inhibitor or statins, reducing mortality and cardiovascular morbidity in patients with established cardiovascular disease. Statins therefore have a place in the secondary prevention of cardiovascular disease. Recent experimental and clinical studies suggest that statins may exert vascular protective effect beyond cholesterol reduction. The cholesterol-independet or “pleiotropic” effects of statin include the upregulation and activation of endothelial nitric acid synthase (eNOS that can increase nitric oxide (NO production. Augmentation of NO production increases cerebral blood flow, which can lead to neuroprotection during brain ischaemia. By inhibiting mevalonate synthesis, statins prevent the formation of several isoprenoids (including farnesylpyrophosphate and geranylgeranylpyrophosphate. Inhibiting geranylgeranylation of RhoA small G proteins increases the stability of eNOS mRNA through the remodeling of endothelial actin microfilamens. Moreover, statins directly increase eNOS activity within minutes by activating the pathway involving phosphoinositide 3-kinase and protein kinase B. In the secondary prevention of stroke, the use of statins reduces the incidence of either recurrent stroke or other major vascular events and treatment should be initiated soon after the event. The use of statins does not increase hemorrhagic stroke or cancer and may also favor atherosclerotic plaque regression.

  20. Pleiotropic effects of statins in stroke prevention

    Directory of Open Access Journals (Sweden)

    Yenny Yenny

    2016-02-01

    Full Text Available Cardiovascular disease is the leading cause of death and disability, and  contributes substantially to healthcare budgets. The lipid-lowering drugs, 3-hydroxy-3-methylgulutaryl-coenzyme A (HMG-CoA reductase inhibitor or statins, reducing mortality and cardiovascular morbidity in patients with established cardiovascular disease. Statins therefore have a place in the secondary prevention of cardiovascular disease. Recent experimental and clinical studies suggest that statins may exert vascular protective effect beyond cholesterol reduction. The cholesterol-independet or “pleiotropic” effects of statin include the upregulation and activation of endothelial nitric acid synthase (eNOS that can increase nitric oxide (NO production. Augmentation of NO production increases cerebral blood flow, which can lead to neuroprotection during brain ischaemia. By inhibiting mevalonate synthesis, statins prevent the formation of several isoprenoids (including farnesylpyrophosphate and geranylgeranylpyrophosphate. Inhibiting geranylgeranylation of RhoA small G proteins increases the stability of eNOS mRNA through the remodeling of endothelial actin microfilamens. Moreover, statins directly increase eNOS activity within minutes by activating the pathway involving phosphoinositide 3-kinase and protein kinase B. In the secondary prevention of stroke, the use of statins reduces the incidence of either recurrent stroke or other major vascular events and treatment should be initiated soon after the event. The use of statins does not increase hemorrhagic stroke or cancer and may also favor atherosclerotic plaque regression.

  1. Statin use and risk of endometrial cancer

    DEFF Research Database (Denmark)

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

    2017-01-01

    INTRODUCTION: Laboratory and epidemiological evidence have suggested that statin use may protect against the development of certain cancers, including endometrial cancer. In a nationwide registry-based case-control study, we examined the association between statin use and risk of endometrial cancer....... MATERIAL AND METHODS: Cases were female residents of Denmark with a primary diagnosis of endometrial cancer during 2000-2009. For each case, we selected 15 female population controls matched on date of birth (±one month) using risk-set sampling. Ever use of statin was defined as two or more prescriptions...... 5382 endometrial cancer cases and 72 127 population controls. We observed no association between ever use of statins and endometrial cancer risk (OR 1.03, 95% CI 0.94-1.14). In addition, endometrial cancer risk did not vary substantially with duration or intensity of statin use. Stratification by type...

  2. STATINS AND URSODEOXYCHOLIC ACID: COOPERATION OR NEUTRALITY?

    Directory of Open Access Journals (Sweden)

    I. N. Grigorieva

    2016-01-01

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

  3. Red Yeast Rice Preparations: Are They Suitable Substitutions for Statins?

    Science.gov (United States)

    Dujovne, Carlos A

    2017-10-01

    Red yeast rice, a commercially available food supplement known to reduce serum cholesterol, has been repeatedly advocated as alternative therapy for hypercholesterolemic patients that refuse statins, cannot tolerate statin therapy's side effects, or request a "naturopathic" medicine. Red yeast rice contains a fungus (Monascus purpureus), which was utilized in the original production of lovastatin (MEVACOR, Merck & Co, Whitehouse Station, NJ), the first marketed pharmaceutical statin, and is chemically identical to such product. Their identical properties account for the similarity in therapeutic and side effects of red yeast rice and lovastatin. The red yeast rice ingredient that blocks cholesterol production is monacolin K. Because red yeast rice preparations have large variability in monacolin K content, predicting or understanding dose-related efficacy and side-effect risks of red yeast rice is practically impossible. The lipid-regulating potency of red yeast rice in commercial preparations was found to be extensively different according to the number or concentration of monacolin K they possess. Furthermore, more than one type of monacolin was found in different preparations (or batches) of red yeast rice. Other ingredients found in red yeast rice are also known to be potentially toxic. The US Food and Drug Administration issued warnings to consumers in 2007 and in 2013 against taking red yeast rice products due to the lack of assurance about its efficacy, safety, and lack of standardized preparation methods. This article discusses my clinical trial results with red yeast rice, reviews the literature on its therapeutic and side effects, and discusses why red yeast rice is not an acceptable substitution for statins. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Expert opinion: the therapeutic challenges faced by statin intolerance.

    Science.gov (United States)

    Patel, Jaideep; Martin, Seth S; Banach, Maciej

    2016-08-01

    Statin intolerance is largely defined by muscle related symptoms, leading to intolerability and cessation. The nocebo effect coupled with the challenges of diagnosing statin myopathy undermines drug adherence that is critical for achieving the benefits of lipid-lowering and cardiovascular risk reduction. A temporal relationship should be made between the initiation of therapy and development of symptoms to aid in diagnosis. The mainstay of treatment is statin cessation or statin dose reduction and evaluation of alternative causes for muscle related symptoms. Most symptoms usually resolve within 2 weeks of discontinuing therapy. The patient can be re-challenged with the same statin at a lower dose or an alternative statin. Non-statin lipid lowering therapies offer an alternative to patients who cannot tolerate statins. We discuss current guideline-focused management of patients with statin intolerance. When initiating statin therapy, attention to risk factors for statin intolerance is strongly recommended. Most patients will tolerate some degree of statin therapy; thus statin re-challenge is advisable. If alternative dosing regimens are not tolerated, non-statin medications are acceptable alternatives. To limit errors in the diagnosis of statin intolerance, improvements in clinician-patient communication about the side effects and benefits of statins should be attempted.

  5. Monitoring the hemostasis with rotation thromboelastometry in patients with acute STEMI on dual antiplatelet therapy

    Science.gov (United States)

    Samoš, Matej; Stančiaková, Lucia; Duraj, Lukáš; Kovář, František; Fedor, Marián; Šimonová, Radoslava; Bolek, Tomáš; Galajda, Peter; Staško, Ján; Kubisz, Peter; Mokáň, Marián

    2017-01-01

    Abstract Rotation thromboelastometry (ROTEM) is a viscoelastometric point-of-care-test for the complex evaluation of changes in hemostasis, performed in whole blood. However, no prospective study evaluating the efficacy of the antiplatelet therapy using ROTEM was performed. Fifty-six patients (34 men, 22 women, mean age 67.75 years, and age range 34–88 years) with acute ST-elevation myocardial infarction (STEMI), treated with dual antiplatelet therapy, undergoing urgent coronary angiography and percutaneous coronary intervention (PCI) of culprit coronary lesion were included. Three blood samples were taken (sample 1 taken before the urgent coronary angiography, sample 2 in 24 hours after the admission, and sample 3 in 30 days after acute STEMI). Twenty-one healthy blood donors (17 men, 4 women, mean age 50.38 years, and age range 40–74 years) were recruited as the control group. Blood samples were tested with ROTEM Gamma (Pentapharm GmbH, Munich, Germany) and light transmission aggregometry (LTA). Clotting time (CT) was significantly prolonged and maximum clot firmness (MCF) was significantly higher in patients compared to controls. Mean platelet aggregation after the induction with arachidonic acid (33.2% vs 74.6% in sample 1 and 21.1% vs 74.6% in sample 2), as well as adenosine diphosphate (51.4% vs 72.7% in sample 1 and 37.1% vs 72.7% in sample 2), were significantly lower in patients with acute STEMI. Significantly prolonged CT and increased MCF was found in patients with acute STEMI. This study confirmed the ability of ROTEM to identify changes in hemostasis in ACS patients on antithrombotic therapy. PMID:28178148

  6. Continuous quality improvement process pin-points delays, speeds STEMI patients to life-saving treatment.

    Science.gov (United States)

    2011-11-01

    Using a multidisciplinary team approach, the University of California, San Diego, Health System has been able to significantly reduce average door-to-balloon angioplasty times for patients with the most severe form of heart attacks, beating national recommendations by more than a third. The multidisciplinary team meets monthly to review all cases involving patients with ST-segment-elevation myocardial infarctions (STEMI) to see where process improvements can be made. Using this continuous quality improvement (CQI) process, the health system has reduced average door-to-balloon times from 120 minutes to less than 60 minutes, and administrators are now aiming for further progress. Among the improvements instituted by the multidisciplinary team are the implementation of a "greeter" with enough clinical expertise to quickly pick up on potential STEMI heart attacks as soon as patients walk into the ED, and the purchase of an electrocardiogram (EKG) machine so that evaluations can be done in the triage area. ED staff have prepared "STEMI" packets, including items such as special IV tubing and disposable leads, so that patients headed for the catheterization laboratory are prepared to undergo the procedure soon after arrival. All the clocks and devices used in the ED are synchronized so that analysts can later review how long it took to complete each step of the care process. Points of delay can then be targeted for improvement.

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

    Science.gov (United States)

    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

  8. Statin prescribing for people with severe mental illnesses: a staggered cohort study of 'real-world' impacts.

    Science.gov (United States)

    Blackburn, R; Osborn, D; Walters, K; Falcaro, M; Nazareth, I; Petersen, I

    2017-03-07

    To estimate the 'real-world effectiveness of statins for primary prevention of cardiovascular disease (CVD) and for lipid modification in people with severe mental illnesses (SMI), including schizophrenia and bipolar disorder. Series of staggered cohorts. We estimated the effect of statin prescribing on CVD outcomes using a multivariable Poisson regression model or linear regression for cholesterol outcomes. 587 general practice (GP) surgeries across the UK reporting data to The Health Improvement Network. All permanently registered GP patients aged 40-84 years between 2002 and 2012 who had a diagnosis of SMI. Exclusion criteria were pre-existing CVD, statin-contraindicating conditions or a statin prescription within the 24 months prior to the study start. One or more statin prescriptions during a 24-month 'baseline' period (vs no statin prescription during the same period). The primary outcome was combined first myocardial infarction and stroke. All-cause mortality and total cholesterol concentration were secondary outcomes. We identified 2944 statin users and 42 886 statin non-users across the staggered cohorts. Statin prescribing was not associated with significant reduction in CVD events (incident rate ratio 0.89; 95% CI 0.68 to 1.15) or all-cause mortality (0.89; 95% CI 0.78 to 1.02). Statin prescribing was, however, associated with statistically significant reductions in total cholesterol of 1.2 mmol/L (95% CI 1.1 to 1.3) for up to 2 years after adjusting for differences in baseline characteristics. On average, total cholesterol decreased from 6.3 to 4.6 in statin users and 5.4 to 5.3 mmol/L in non-users. We found that statin prescribing to people with SMI in UK primary care was effective for lipid modification but not CVD events. The latter finding may reflect insufficient power to detect a smaller effect size than that observed in randomised controlled trials of statins in people without SMI. Published by the BMJ Publishing Group Limited. For

  9. Distribution of creatine kinase in the general population: Implications for statin therapy

    NARCIS (Netherlands)

    Brewster, Lizzy M.; Mairuhu, Gideon; Sturk, August; van Montfrans, Gert A.

    2007-01-01

    Background Eligible subjects with mildly elevated serum creatine kinase (CK) activity are often excluded before randomization in statin trials, but patients may potentially be misclassified as having hyperCKemia when inappropriate reference limits are used. Little information is usually given

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Brennan, Emily T; Joy, Tisha R

    2017-05-01

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

  12. Statins and risk of breast cancer recurrence

    Directory of Open Access Journals (Sweden)

    Sakellakis M

    2016-11-01

    Full Text Available Minas Sakellakis,1 Karolina Akinosoglou,1 Anastasia Kostaki,2 Despina Spyropoulou,1 Angelos Koutras,1 1Department of Medicine, Division of Oncology, University Hospital, Patras Medical School, Patras, 2Department of Statistics, Athens University of Economics and Business, Athens, Greece Background: The primary end point of our study was to test whether the concurrent use of a statin is related to a lower risk of recurrence and increased relapse-free survival in patients with early breast cancer. Materials and methods: We reviewed 610 female patients with stage I, II, or III breast cancer who had been surgically treated and who had subsequently received at least adjuvant chemotherapy in order to prevent recurrence. Results: Among the 610 patients with breast cancer, 83 (13.6% were receiving a statin on a chronic basis for other medical purposes. Overall, statin users displayed longer mean relapse-free survival (16.6 vs 10.2 years, P=0.028. After data had been adjusted for patient and disease characteristics, statin users maintained a lower risk of recurrence. This favorable outcome in statin users was particularly evident when we included only younger patients in the analysis (20 vs 10 years, P=0.006. Conclusion: Statins may be linked to a favorable outcome in early breast cancer patients, especially in younger age-groups. Keywords: statins, breast, cancer, adjuvant, recurrence

  13. Equity in statin use in New Zealand

    Directory of Open Access Journals (Sweden)

    Norris P

    2014-03-01

    Full Text Available INTRODUCTION: Preventive medications such as statins are used to reduce cardiovascular risk. There is some evidence to suggest that people of lower socioeconomic position are less likely to be prescribed statins. In New Zealand, Maori have higher rates of cardiovascular disease. AIM: This study aimed to investigate statin utilisation by socioeconomic position and ethnicity in a region of New Zealand. METHODS: This was a cross-sectional study in which data were collected on all prescriptions dispensed from all pharmacies in one city during 2005/6. Linkage with national datasets provided information on patients' age, gender and ethnicity. Socioeconomic position was identified using the New Zealand Index of Socioeconomic Deprivation 2006. RESULTS: Statin use increased with age until around 75 years. Below age 65 years, those in the most deprived socioeconomic areas were most likely to receive statins. In the 55-64 age group, 22.3% of the most deprived population received a statin prescription (compared with 17.5% of the mid and 18.6% of the least deprived group. At ages up to 75 years, use was higher amongst Maori than non-Maori, particularly in middle age, where Maori have a higher risk of cardiovascular disease. In the 45-54 age group, 11.6% of Maori received a statin prescription, compared with 8.7% of non-Maori. DISCUSSION: Statin use approximately matched the pattern of need, in contrast to other studies which found under-treatment of people of low socioeconomic position. A PHARMAC campaign to increase statin use may have increased use in high-risk groups in New Zealand.

  14. Patient co-payment and adherence to statins: a review and case studies.

    Science.gov (United States)

    Simoens, Steven; Sinnaeve, Peter R

    2014-02-01

    This study aims to review the international literature about whether there is an association between co-payment and statin adherence, and to present case studies to illustrate the impact of a reduction in patient co-payment associated with generic drugs on improving therapy adherence. Studies that examined the impact of patient co-payment on statin adherence were identified in PubMed, Cochrane Central Register of Controlled Trials and EconLit up to January 2013. A standardized data extraction form was completed for each included study, collecting information about country, sample, setting, adherence measure, design, results about the impact of co-payment on statin adherence, and methodological quality. Two cases from the outpatient clinic of one the authors (PRS) were added. The literature supported a statistically significant negative association between co-payment and statin adherence. This association appeared to be influenced by the absolute level of co-payments, the size of the co-payment change, whether co-payment increases or decreases, the time horizon over which the impact of a co-payment change is examined, the type of drug for which co-payment changes (e.g. generic or branded drug), the availability of alternative drugs and switching behaviour. Two case studies illustrated that cost issues are important to patients and that patient adherence to statin therapy improved following a switch to generic statins. Current studies have demonstrated that statin adherence is influenced by co-payment and a range of patient, physician and pharmacy characteristics. Nevertheless, the power of these models to explain the variation in adherence remains limited.

  15. Non-response to (statin) therapy

    DEFF Research Database (Denmark)

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

    2016-01-01

    : Baseline characteristics of non-responders to statin therapy (≤10 % LDL-C reduction) were compared with those of high responders (>40 % LDL-C reduction) through a linear regression analysis. In addition, pharmacogenetic candidate gene analysis was performed to show the effect of excluding non......-responders from the analysis. RESULTS: Non-responders to statin therapy were younger (p = 0.001), more often smoked (p ....035) compared to subjects who highly responded to pravastatin treatment. Moreover, excluding non-responders from pharmacogenetic studies yielded more robust results, as standard errors decreased. CONCLUSION: Our results suggest that non-responders to statin therapy are more likely to actually be non...

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

    Directory of Open Access Journals (Sweden)

    Benes LB

    2016-12-01

    Full Text Available Lane B Benes1, Nikhil S Bassi2, Michael H Davidson1 1Department of Medicine, Section of Cardiology, 2Department of Medicine, University of Chicago, Chicago, IL, USA Abstract: The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin. Keywords: omega-3 carboxylic acids, non-HDL-C, hypertriglyceridemia, residual risk, statin

  17. Anti inflammatory effects of statin in COPD

    Directory of Open Access Journals (Sweden)

    Nasef Abdelsalam Rezk

    2013-01-01

    Conclusion: We conclude that statin may lower the exacerbation in patients with chronic obstructive lung diseases and may lower the total cell count of inflammatory cells, sputum leptin and neutrophils.

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

    Directory of Open Access Journals (Sweden)

    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

  19. Statins: antimicrobial resistance breakers or makers?

    Directory of Open Access Journals (Sweden)

    Humphrey H.T. Ko

    2017-10-01

    Full Text Available Introduction The repurposing of non-antibiotic drugs as adjuvant antibiotics may help break antimicrobial resistance (AMR. Statins are commonly prescribed worldwide to lower cholesterol. They also possess qualities of AMR “breakers”, namely direct antibacterial activity, synergism with antibiotics, and ability to stimulate the host immune system. However, statins’ role as AMR breakers may be limited. Their current extensive use for cardiovascular protection might result in selective pressures for resistance, ironically causing statins to be AMR “makers” instead. This review examines statins’ potential as AMR breakers, probable AMR makers, and identifies knowledge gaps in a statin-bacteria-human-environment continuum. The most suitable statin for repurposing is identified, and a mechanism of antibacterial action is postulated based on structure-activity relationship analysis. Methods A literature search using keywords “statin” or “statins” combined with “minimum inhibitory concentration” (MIC was performed in six databases on 7th April 2017. After screening 793 abstracts, 16 relevant studies were identified. Unrelated studies on drug interactions; antifungal or antiviral properties of statins; and antibacterial properties of mevastatin, cerivastatin, antibiotics, or natural products were excluded. Studies involving only statins currently registered for human use were included. Results Against Gram-positive bacteria, simvastatin generally exerted the greatest antibacterial activity (lowest MIC compared to atorvastatin, rosuvastatin, and fluvastatin. Against Gram-negative bacteria, atorvastatin generally exhibited similar or slightly better activity compared to simvastatin, but both were more potent than rosuvastatin and fluvastatin. Discussion Statins may serve as AMR breakers by working synergistically with existing topical antibiotics, attenuating virulence factors, boosting human immunity, or aiding in wound healing. It

  20. 27. The impact of introduction of code-stemi program on clinical outcomes of acute st-elevation myocardial infarction (stemi patients undergoing primary pci: Single center study in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    A. ALYAHYA

    2016-07-01

    Full Text Available This study was conducted to evaluate the effect of direct Emergency Department activation of the Catheterization Lab on door to balloon (D2B time and outcomes of acute ST-elevation myocardial infarction (STEMI patients in King Khalid University Hospital (KKUH. Establishing dedicated comprehensive STEMI programs aiming at reducing door to balloon time will impact favourably the outcomes of patients presenting with acute STEMI. This was a retrospective cohort study that involved 100 patients in KKUH who presented with acute STEMI and underwent primary percutaneous intervention (PPCI, between June 2010 and January 2015. The cohort was divided into two groups, the first group consisted of 50 patients who were treated before establishing the Code-STEMI protocol, whereas the second group were 50 patients who were treated according to the protocol, which was implemented in June 2013. Code-STEMI program is a comprehensive program that includes direct activation of the cath lab team using a single call system, data monitoring and feedback, and standardized order forms. The mean age in both groups was 54 ± 12 years and 86% (43 and 94% (47 of the patients in the two groups were males, respectively. 90% (90 of patients in both groups had one or more comorbidities.Code-STEMI group had a significantly lower D2BT with 70% of patients treated within the recommended 90 minutes (median = 76.5 min, IQR: 63–90 min compared to only 26% of pre code-STEMI patients (median = 107 min, IQR: 74–149 min In-hospital complications were lower in the Code-STEMI group; however, the only statistically significant reduction was in non-fatal re-infarction, (8% vs. 0%, p = 0.043. In addition, the number of patients with more than one in-hospital complications was also reduced by 20%.Implementation of direct ER-Catheterization lab activation protocol was associated with a significant reduction in D2B time, and an overall improvement of in-hospital outcomes.

  1. Smartphone ECG for evaluation of STEMI: results of the ST LEUIS Pilot Study.

    Science.gov (United States)

    Muhlestein, Joseph Boone; Le, Viet; Albert, David; Moreno, Fidela Ll; Anderson, Jeffrey L; Yanowitz, Frank; Vranian, Robert B; Barsness, Gregory W; Bethea, Charles F; Severance, Harry W; Ramo, Barry; Pierce, John; Barbagelata, Alejandro; Muhlestein, Joseph Brent

    2015-01-01

    12-lead ECG is a critical component of initial evaluation of cardiac ischemia, but has traditionally been limited to large, dedicated equipment in medical care environments. Smartphones provide a potential alternative platform for the extension of ECG to new care settings and to improve timeliness of care. To gain experience with smartphone electrocardiography prior to designing a larger multicenter study evaluating standard 12-lead ECG compared to smartphone ECG. 6 patients for whom the hospital STEMI protocol was activated were evaluated with traditional 12-lead ECG followed immediately by a smartphone ECG using right (VnR) and left (VnL) limb leads for precordial grounding. The AliveCor™ Heart Monitor was utilized for this study. All tracings were taken prior to catheterization or immediately after revascularization while still in the catheterization laboratory. The smartphone ECG had excellent correlation with the gold standard 12-lead ECG in all patients. Four out of six tracings were judged to meet STEMI criteria on both modalities as determined by three experienced cardiologists, and in the remaining two, consensus indicated a non-STEMI ECG diagnosis. No significant difference was noted between VnR and VnL. Smartphone based electrocardiography is a promising, developing technology intended to increase availability and speed of electrocardiographic evaluation. This study confirmed the potential of a smartphone ECG for evaluation of acute ischemia and the feasibility of studying this technology further to define the diagnostic accuracy, limitations and appropriate use of this new technology. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. System delay and mortality among patients with STEMI treated with primary percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Terkelsen, Christian Juhl; Sørensen, Jacob Thorsted; Maeng, Michael

    2010-01-01

    Timely reperfusion therapy is recommended for patients with ST-segment elevation myocardial infarction (STEMI), and door-to-balloon delay has been proposed as a performance measure in triaging patients for primary percutaneous coronary intervention (PCI). However, focusing on the time from first...... contact with the health care system to the initiation of reperfusion therapy (system delay) may be more relevant, because it constitutes the total time to reperfusion modifiable by the health care system. No previous studies have focused on the association between system delay and outcome in patients...

  3. RHOA is a modulator of the cholesterol-lowering effects of statin.

    Directory of Open Access Journals (Sweden)

    Marisa W Medina

    Full Text Available Although statin drugs are generally efficacious for lowering plasma LDL-cholesterol levels, there is considerable variability in response. To identify candidate genes that may contribute to this variation, we used an unbiased genome-wide filter approach that was applied to 10,149 genes expressed in immortalized lymphoblastoid cell lines (LCLs derived from 480 participants of the Cholesterol and Pharmacogenomics (CAP clinical trial of simvastatin. The criteria for identification of candidates included genes whose statin-induced changes in expression were correlated with change in expression of HMGCR, a key regulator of cellular cholesterol metabolism and the target of statin inhibition. This analysis yielded 45 genes, from which RHOA was selected for follow-up because it has been found to participate in mediating the pleiotropic but not the lipid-lowering effects of statin treatment. RHOA knock-down in hepatoma cell lines reduced HMGCR, LDLR, and SREBF2 mRNA expression and increased intracellular cholesterol ester content as well as apolipoprotein B (APOB concentrations in the conditioned media. Furthermore, inter-individual variation in statin-induced RHOA mRNA expression measured in vitro in CAP LCLs was correlated with the changes in plasma total cholesterol, LDL-cholesterol, and APOB induced by simvastatin treatment (40 mg/d for 6 wk of the individuals from whom these cell lines were derived. Moreover, the minor allele of rs11716445, a SNP located in a novel cryptic RHOA exon, dramatically increased inclusion of the exon in RHOA transcripts during splicing and was associated with a smaller LDL-cholesterol reduction in response to statin treatment in 1,886 participants from the CAP and Pravastatin Inflamation and CRP Evaluation (PRINCE; pravastatin 40 mg/d statin clinical trials. Thus, an unbiased filter approach based on transcriptome-wide profiling identified RHOA as a gene contributing to variation in LDL-cholesterol response to statin

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

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G

    2014-01-01

    BACKGROUND: The role of statins in the development of microvascular disease in patients with diabetes is unknown. We tested the hypothesis that statin use increases the risk of diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and gangrene of the foot in individuals with diabetes...... Statistics. We randomly selected 15,679 individuals from the database who had used statins regularly until their diagnosis of diabetes (statin users) and matched them in a 1:3 ratio with 47,037 individuals who had never used statins before diagnosis (non-statin users). Our primary outcome was to compare...... 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...

  5. Comprehensive efforts to increase adherence to statin therapy

    DEFF Research Database (Denmark)

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

    2017-01-01

    There is compelling evidence that statin therapy improves cardiovascular morbidity and mortality. Unfortunately, statin adherence is far from optimal regarding initiation, execution and persistence of treatment over time.26 Poor adherence to statin therapy is associated with a significantly...... increased risk of cardiovascular events and mortality. Evidence-based steps to improve adherence are available and should be taken in order to improve patient outcomes. Reinforcing statin adherence appears to have at least as strong beneficial effects as introducing a new drug....

  6. Statin therapy for the octogenarian? | Blom | Journal of ...

    African Journals Online (AJOL)

    A meta-analysis of secondary prevention, with patients aged 65-82 years at randomisation, supported statin prescription in this age group, as statin therapy was associated with relative risk reduction similar ... Currently there is no definite evidence that statin therapy prevents or ameliorates cognitive impairment or dementia.

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  8. A systematic review and economic evaluation of statins for the prevention of coronary events.

    Science.gov (United States)

    Ward, S; Lloyd Jones, M; Pandor, A; Holmes, M; Ara, R; Ryan, A; Yeo, W; Payne, N

    2007-04-01

    To evaluate the clinical effectiveness and cost-effectiveness of statins for the primary and secondary prevention of cardiovascular events in adults with, or at risk of, coronary heart disease (CHD). Electronic databases were searched between November 2003 and April 2004. A review was undertaken to identify and evaluate all literature relating to the clinical and cost effectiveness of statins in the primary and secondary prevention of CHD and cardiovascular disease (CVD) in the UK. A Markov model was developed to explore the costs and health outcomes associated with a lifetime of statin treatment using a UK NHS perspective. Thirty-one randomised studies were identified that compared a statin with placebo or with another statin, and reported clinical outcomes. Meta-analysis of the available data from the placebo-controlled studies indicates that, in patients with, or at risk of, CVD, statin therapy is associated with a reduced relative risk of all cause mortality, cardiovascular mortality, CHD mortality and fatal myocardial infarction (MI), but not of fatal stroke. It is also associated with a reduced relative risk of morbidity [non-fatal stroke, non-fatal MI, transient ischaemic attack (TIA), unstable angina] and of coronary revascularisation. It is hardly possible, on the evidence available from the placebo-controlled trials, to differentiate between the clinical efficacy of atorvastatin, fluvastatin, pravastatin and simvastatin. However, there is some evidence from direct comparisons between statins to suggest that atorvastatin may be more effective than pravastatin in patients with symptomatic CHD. There is limited evidence for the effectiveness of statins in different subgroups. Statins are generally considered to be well tolerated and to have a good safety profile. This view is generally supported both by the evidence of the trials included in this review and by postmarketing surveillance data. Increases in creatine kinase and myopathy have been reported, but

  9. Plasma triglycerides and cardiovascular events in the Treating to New Targets and Incremental Decrease in End-Points through Aggressive Lipid Lowering trials of statins in patients with coronary artery disease

    DEFF Research Database (Denmark)

    Faergeman, Ole; Holme, Ingar; Fayyad, Rana

    2009-01-01

    We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg...... adjusting for age, gender, and study, risk of CVEs increased with increasing TGs (p relation of TGs...

  10. Mechanisms of bone anabolism regulated by statins.

    Science.gov (United States)

    Ruan, Feng; Zheng, Qiang; Wang, Jinfu

    2012-12-01

    Osteoporosis is a common disease in the elderly population. The progress of this disease results in the reduction of bone mass and can increase the incidence of fractures. Drugs presently used clinically can block the aggravation of this disease. However, these drugs cannot increase the bone mass and may result in certain side effects. Statins, also known as HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, have been widely prescribed for CVD (cardiovascular disease) for decades. Nonetheless, several studies have demonstrated that statins exert bone anabolic effect and may be helpful for the treatment of osteoporosis. Several experiments have analysed the mechanisms of bone anabolism regulated by statins. In the present paper, we review the mechanisms of promoting osteogenesis, suppressing osteoblast apoptosis and inhibiting osteoclastogenesis.

  11. Evaluation of acute ischemia in pre-procedure ECG predicts myocardial salvage after primary PCI in STEMI patients with symptoms >12hours

    DEFF Research Database (Denmark)

    Fakhri, Yama; Busk, Martin; Schoos, Mikkel Malby

    2016-01-01

    BACKGROUND: Primary percutaneous coronary intervention (pPCI) is recommended in patients with ST Elevation Myocardial Infarction (STEMI) and symptom duration <12hours. However, a considerable amount of myocardium might still be salvaged in STEMI patients with symptom durations >12hours (late-pres...

  12. A Prospective Evaluation of a Pre-Specified Absorb BVS Implantation Strategy in ST-Segment Elevation Myocardial Infarction: The BVS STEMI STRATEGY-IT Study.

    Science.gov (United States)

    Ielasi, Alfonso; Campo, Gianluca; Rapetto, Claudio; Varricchio, Attilio; Cortese, Bernardo; Brugaletta, Salvatore; Geraci, Salvatore; Vicinelli, Paolo; Scotto di Uccio, Fortunato; Secco, Gioel Gabrio; Poli, Arnaldo; Nicolini, Elisa; Ishida, Kohki; Latib, Azeem; Tespili, Maurizio

    2017-09-25

    The aim of this study was to assess the feasibility and clinical results following a pre-specified bioresorbable scaffold (Absorb BVS) implantation strategy in patients with ST-segment elevation myocardial infarction (STEMI). Concerns were raised about the safety of Absorb because a non-negligible rate of thrombosis was reported within 30 days and at midterm follow-up after primary percutaneous coronary intervention. This was a prospective, multicenter study of patients with STEMI (strategy in real-world patients with STEMI undergoing primary percutaneous coronary intervention was feasible and associated with a low 30-day device-oriented composite endpoint rate. Mid- and long-term follow-up is strongly needed to eventually confirm these early results. (Use of BVS in ST-Segment Elevation Myocardial Infarction [STEMI]: The BVS STEMI STRATEGY-IT Prospective Registry [STRATEGY-IT]; NCT02601781). Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  13. The use of statins in primary prevention

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. A Clinical Evaluation of Statin Pleiotropy: Statins Selectively and Dose-Dependently Reduce Vascular Inflammation

    NARCIS (Netherlands)

    Meij, E. van der; Koning, G.G.; Vriens, P.W.; Peeters, M.F.; Meijer, C.A.; Kortekaas, K.E.; Dalman, R.L.; Bockel, J.H. van; Hanemaaijer, R.; Kooistra, T.; Kleemann, R.; Lindeman, J.H.N.

    2013-01-01

    Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike

  16. A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation

    NARCIS (Netherlands)

    Meij, E van der; Koning, G.G.; Vriens, P.W.H.E.; Peeters, M.F.; Meijer, C.A.; Kortekaas, K.E.; Dalman, R.L.; Bockel, J.H. van; Hanemaaijer, R.; Kooistra, T.; Kleemann, R.; Lindeman, J.H.

    2013-01-01

    Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA) are part of the atherosclerotic spectrum of diseases. Unlike

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

    Directory of Open Access Journals (Sweden)

    Josephine H. Li

    2014-03-01

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

  18. Prehospital electrocardiographic acuteness score of ischemia is inversely associated with neurohormonal activation in STEMI patients with severe ischemia

    DEFF Research Database (Denmark)

    Fakhri, Yama; Schoos, Mikkel Malby; Sejersten-Ripa, Maria

    2017-01-01

    BACKGROUND: Elevated levels of N-terminal pro brain natriuretic peptide (NT-proBNP) are associated with adverse cardiovascular outcome after ST elevation myocardial infarction (STEMI). We hypothesized that decreasing acuteness-score (based on the electrocardiographic score by Anderson-Wilkins acu...

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

    NARCIS (Netherlands)

    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

  20. Dynamic changes in sRAGE levels and relationship with cardiac function in STEMI patients

    DEFF Research Database (Denmark)

    Jensen, Louise J N; Lindberg, Søren; Hoffmann, Søren

    2015-01-01

    OBJECTIVES: Soluble receptor of advanced glycation end-products (sRAGE) may be a predictive biomarker in coronary artery disease (CAD). Patients with acute myocardial infarction (AMI) have higher sRAGE levels compared to healthy subjects. Accordingly, the aim of this study was to investigate...... the dynamic changes in sRAGE levels during AMI and relationship with cardiac dysfunction. DESIGN AND METHODS: We prospectively included 80 patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI). sRAGE concentrations were measured before p......PCI, immediately after pPCI and again on the first and second following days. Left ventricular ejection fraction (LVEF) was evaluated 1-3 days after the pPCI and again at a median of 7months by echocardiography, and infarct size was measured by cardiac magnetic resonance. RESULTS: sRAGE levels were high...

  1. MR-proANP improves prediction of mortality and cardiovascular events in patients with STEMI

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan Skov; Pedersen, Sune H

    2015-01-01

    ANP is elevated in cardiovascular disease and predicts outcome in heart failure. However, knowledge of the prognostic value in acute myocardial infarction remains limited. METHODS: We prospectively included 680 patients with STEMI treated with primary-PCI, from September 2006 to December 2008. Blood samples were...... drawn immediately before PCI. Plasma MR-proANP was measured using an automated processing assay. Endpoints were all-cause mortality (n = 137) and the combined endpoint (n = 170) of major adverse cardiovascular events (MACE) defined as cardiovascular mortality and admission due to recurrent MI, ischaemic...... stroke or heart failure. RESULTS: During 5-year follow-up, MR-proANP was associated with increased risk of all-cause mortality and MACE (both p 

  2. Effects of four antiplatelet/statin combined strategies on immune and inflammatory responses in patients with acute myocardial infarction undergoing pharmacoinvasive strategy: Design and rationale of the B and T Types of Lymphocytes Evaluation in Acute Myocardial Infarction (BATTLE-AMI) study: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Fonseca, Francisco A H; Izar, Maria Cristina; Maugeri, Ieda M L; Berwanger, Otavio; Damiani, Lucas P; Pinto, Ibraim M; Szarf, Gilberto; França, Carolina N; Bianco, Henrique T; Moreira, Flavio T; Caixeta, Adriano; Alves, Claudia M R; Soriano Lopes, Aline; Klassen, Aline; Tavares, Marina F M; Fonseca, Henrique A; Carvalho, Antonio C C

    2017-12-19

    Early reperfusion of the occluded coronary artery during acute myocardial infarction is considered crucial for reduction of infarcted mass and recovery of ventricular function. Effective microcirculation and the balance between protective and harmful lymphocytes may have roles in reperfusion injury and may affect final ventricular remodeling. BATTLE-AMI is an open-label, randomized trial comparing the effects of four therapeutic strategies (rosuvastatin/ticagrelor, rosuvastatin/clopidogrel, simvastatin plus ezetimibe/ticagrelor, or simvastatin plus ezetimibe/clopidogrel) on infarcted mass and left ventricular ejection fraction (LVEF) (blinded endpoints) in patients with ST-segment elevation myocardial infarction submitted to fibrinolytic therapy before coronary angiogram (pharmacoinvasive strategy). All patients (n = 300, 75 per arm) will be followed up for six months. The effects of treatment on subsets of B and T lymphocytes will be determined by flow-cytometry/ELISPOT and will be correlated with the infarcted mass, LVEF, and microcirculation perfusion obtained by cardiac magnetic resonance imaging. The primary hypothesis is that the combined rosuvastatin/ticagrelor therapy will be superior to other therapies (particularly for the comparison with simvastatin plus ezetimibe/clopidogrel) for the achievement of better LVEF at 30 days (primary endpoint) and smaller infarcted mass (secondary endpoint) at 30 days and six months. The trial will also evaluate the improvement in the immune/inflammatory responses mediated by B and T lymphocytes. Omics field (metabolomics and proteomics) will help to understand these responses by molecular events. BATTLE-AMI is aimed to (1) evaluate the role of subsets of lymphocytes on microcirculation improvement and (2) show how the choice of statin/antiplatelet therapy may affect cardiac remodeling after acute myocardial infarction with ST elevation. ClinicalTrials.gov, NCT02428374 . Registered on 28 September 2014.

  3. Statin and NSAID Use and Prostate Cancer Risk

    Science.gov (United States)

    Coogan, Patricia F.; Kelly, Judith Parsells; Strom, Brian L.; Rosenberg, Lynn

    2010-01-01

    Purpose Some studies have reported reduced risks of advanced, but not early, prostate cancer among statin users, and one study found a reduced risk only among statin users who had also used nonsteroidal anti-inflammatory drugs (NSAIDs). We have previously reported no association between statin use and prostate cancer in our hospital-based Case Control Surveillance Study. The purpose of the present analyses was to update the findings by cancer stage and to evaluate the joint use of statins and NSAIDs. Methods Cases were 1367 men with prostate cancer and controls were 2007 men with diagnoses unrelated to statin or NSAID use. We used multivariable logistic regression analyses to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for statin use compared with no use, and joint use of statin and NSAIDs compared with use of neither. Results The odds ratio among regular statin users was 1.1 (95% CI 0.9–1.5), and odds ratios were similar among early and late stage cancers. The odds ratio among joint statin and NSAID users was 1.1 (95% CI 0.7–1.6). Conclusion The present results do not support a protective effect of statin use, or statin and NSAID use, on the risk of advanced prostate cancer. PMID:20582910

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

    African Journals Online (AJOL)

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

  5. Statin use and Parkinson's disease in Denmark

    DEFF Research Database (Denmark)

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

    2010-01-01

    The objective of this study was to investigate whether statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) use is associated with risk of Parkinson's disease (PD) in Denmark. We identified 1,931 patients with a first time diagnosis of PD reported in hospital or outpatient clinic...

  6. Hypothyroidism as a risk factor for statin intolerance.

    Science.gov (United States)

    Robison, Craig D; Bair, Tami L; Horne, Benjamin D; McCubrey, Ray O; Lappe, Donald L; Muhlestein, Joseph B; Anderson, Jeffrey L

    2014-01-01

    Three-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) are one of the most commonly prescribed classes of medications because of their proven cardiovascular benefits. However, statin intolerance occurs in 5% to 20% of patients. Understanding the basis for statin intolerance remains a key issue in preventive medicine. To evaluate the association of statin intolerance with hypothyroidism in a large integrated health care system, including its sex-specific relationship and subsequent statin rechallenge and prescription history. The Intermountain Healthcare electronic medical record database identified patients (n = 2686; males = 1276, females = 1410) with a documentation of intolerance ("allergy") to at least 1 statin. Age and sex similar controls (n = 8103; males = 3892, females = 4211) were identified among patients prescribed statins without documented intolerance. Patients were evaluated for a history of hypothyroidism, development of hypothyroidism, and statin prescription history up to 5 years of follow-up. A total of 30.2% patients (210 males, 16.5%; 602 females, 42.7%) with statin intolerance had a history of hypothyroidism compared with 21.5% of statin-tolerant patients (475 males, 12.2%; 1266 females, 30.1%), for an odds ratio (OR) in the total population of 1.49 (95% confidence interval [CI] 1.34-1.65; P intolerance and hypothyroidism were less likely to be on a statin than their statin-intolerant counterparts without hypothyroidism (hazard ratio 0.84; 95% CI 0.75-0.94; P = .002). Hypothyroidism is more prevalent in those with statin intolerance, both in males and, especially, in females. People with hypothyroidism are less likely to have a prescription for a statin at follow-up than those without hypothyroidism. Copyright © 2014 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  7. [Transport and treatment of patients with STEMI in rural Iceland--Only a few patients receive PPCI within 120 minutes].

    Science.gov (United States)

    Sigmundsson, Thórir S; Arnarson, Daníel; Rafnsson, Arnar; Magnússon, Viðar; Gunnarsson, Gunnar Thór; Thorgeirsson, Gestur

    2016-01-01

    ST-segment Elevation Myocardial Infarction (STEMI) is a life-threatening disease and good outcome depends on early restoration of coronary blood flow. Primary percutaneous coronary intervention (PPCI) is the treatment of choice if performed within 120 minutes of first medical contact (FMC) but in case of anticipated long transport or delays, pre-hospital fibrinolysis is indicated. The aim was to study transport times and adherence to clinical guidelines in patients with STEMI transported from outside of the Reykjavik area to Landspitali University Hospital in Iceland. Retrospective chart review was conducted of all patients diagnosed with STEMI outside of the Reykjavik area and transported to Landspitali University Hospital in Reykjavik in 2011-2012. Descriptive statistical analysis and hypothesis testing was applied. Eighty-six patients had signs of STEMI on electrocardiogram (ECG) at FMC. In southern Iceland nine patients (21%) underwent PPCI within 120 minutes (median 157 minutes) and no patient received fibrinolysis. In northern Iceland and The Vestman Islands, where long transport times are expected, 96% of patients eligible for fibrinolysis (n=31) received appropriate therapy in a median time of 57 minutes. Significantly fewer patients received appropriate anticoagulation treatment with clopidogrel and enoxaparin in southern Iceland compared to the northern part. Mortality rate was 7% and median length of stay in hospital was 6 days. Time from FMC to PPCI is longer than 120 minutes in the majority of cases. Pre-hospital fibrinolysis should be considered as first line treatment in all parts of Iceland outside of the Reykjavik area. Directly electronically transmitted ECGs and contact with cardiologist could hasten diagnosis and decrease risk of unnecessary interhospital transfer. A STEMI database should be established in Iceland to facilitate quality control.

  8. Improving door-to-balloon time by decreasing door-to-ECG time for walk-in STEMI patients.

    Science.gov (United States)

    Coyne, Christopher J; Testa, Nicholas; Desai, Shoma; Lagrone, Joy; Chang, Roger; Zheng, Ling; Kim, Hyung

    2015-01-01

    The American Heart Association/American College of Cardiology guidelines recommend rapid door-to-electrocardiography (ECG) times for patients with ST-segment elevation myocardial infarction (STEMI). Previous quality improvement research at our institution revealed that we were not meeting this benchmark for walk-in STEMI patients. The objective is to investigate whether simple, directed changes in the emergency department (ED) triage process for potential cardiac patients could decrease door-to-ECG times and secondarily door-to-balloon times. We conducted an interventional study at a large, urban, public teaching hospital from April 2010 to June 2012. All patients who walked into the ED with a confirmed STEMI were enrolled in the study. The primary intervention involved creating a chief complaint-based "cardiac triage" designation that streamlined the evaluation of potential cardiac patients. A secondary intervention involved moving our ECG technician and ECG station to our initial triage area. The primary outcome measure was door-to-ECG time and the secondary outcome measure was door-to-balloon time. We enrolled 91 walk-in STEMI patients prior to the intervention period and 141 patients after the invention. We observed statistically significant reductions in door-to-ECG time (43±93 to 30±72 minutes, median 23 to 14 minutes pECG-to-activation time (87±134 to 52±82 minutes, median 43 to 31 minutes pECG completion, walk-in STEMI patients are systematically processed through the ED. This is not only associated with a decrease in door-to-balloon time, but also a decrease in the variability of the time sensitive intervals of door-to-ECG and ECG-to-balloon time.

  9. Preoperative statin therapy decreases early mortality in patients undergoing isolated valve surgery: result from a meta-analysis.

    Science.gov (United States)

    Cheng, Xiaocheng; Hu, Qiongwen; Liu, Zengzhang; Tang, Xuewen

    2015-02-01

    The purpose of this meta-analysis was to assess the role of preoperative statin therapy on adverse cardiovascular events in patients undergoing valve surgery. Meta-analysis of 10 observational studies. Hospital. 22,158 patients. None. The Medline, Cochrane, and Embase databases were searched for clinical studies published up to June 2014. Studies that evaluated the effects of preoperative statin therapy on valve surgery were included. After a literature search in the major databases, 10 observational studies with 22,518 patients were identified. Pool analysis indicated that preoperative statin therapy was associated with a significantly lower risk of early all-cause mortality (Odds ratio [OR]: 0.69; 95% confidence interval [CI] 0.50-0.95, p = 0.03). The benefits of preoperative statin therapy were more obvious in studies with isolated valve surgery, resulting in a 1.9% absolute risk and a 38% odds reduction of early mortality (2.4 v 4.3%; OR: 0.62; 95% CI 0.49-0.77, p<0.0001). A significant reduction by statin therapy also was observed for atrial fibrillation (OR 0.88, 95% CI: 0.80-0.98, p = 0.02). However, statin therapy was not associated with a lower risk of postoperative stroke (OR: 0.74; 95% CI 0.46-1.19, p = 0.21), myocardial infarction (OR: 1.02; 95% CI 0.78-1.34, p = 0.87), and renal failure (OR: 0.91; 95% CI 0.57-1.44, p = 0.68). Preoperative statin therapy was associated with a significantly lower risk of early mortality in patients undergoing isolated valve surgery. A prospective, randomized, controlled trial is warranted. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Statins in the prevention of dementia and Alzheimer's disease: a meta-analysis of observational studies and an assessment of confounding.

    Science.gov (United States)

    Wong, William B; Lin, Vincent W; Boudreau, Denise; Devine, Emily Beth

    2013-04-01

    Studies demonstrate the potential for statins to prevent dementia and Alzheimer's disease (AD), but the evidence is inconclusive. Conduct a meta-analysis to estimate any benefit of statins in preventing dementia and examine the potential effect of study design and confounding on the benefit of statins in dementia. A secondary goal is to explore factors that may elucidate the mechanisms by which statins exert their potentially beneficial effect. Performed systematic literature review to identify relevant publications. Relative risk (RR) estimates were pooled using both fixed and random effect models. Studies were stratified by study design and potential confounding factors. The pooled results for all-type dementia suggest that use of statins is associated with a lower RR of dementia when compared to non-statin users (random effects model: RR 0.82 (95%CI [0.69, 0.97]). The pooled results for AD also suggested a lower RR with statin user compared to non-statin users in random effects models (RR: 0.70, 95% CI [0.60, 0.83]). Study design and methods used to address biases may influence the results. These pooled results suggest that statins may provide a slight benefit in the prevention of AD and all-type dementia. This benefit observed in both disease states should be interpreted with caution as observational studies are subject to bias, and it is possible that the slight benefit observed may disappear when these biases are addressed in a well-designed randomized controlled trial. Copyright © 2012 John Wiley & Sons, Ltd.

  11. A point-by-point response to recent arguments against the use of statins in primary prevention: this statement is endorsed by the American Society for Preventive Cardiology.

    Science.gov (United States)

    Joshi, Parag H; Chaudhari, Sameer; Blaha, Michael J; Jones, Steven R; Martin, Seth S; Post, Wendy S; Cannon, Christopher P; Fonarow, Gregg C; Wong, Nathan D; Amsterdam, Ezra; Hirshfeld, John W; Blumenthal, Roger S

    2012-01-01

    Recently, a debate over the merits of statin therapy in primary prevention was published in the Wall Street Journal. The statin opponent claimed that statins should only be used in secondary prevention and never in any primary-prevention patients at risk for cardiovascular events. In this evidence-based rebuttal to those claims, we review the evidence supporting the efficacy of statin therapy in primary prevention. Cardiovascular risk is a continuum in which those at an elevated risk of events stand to benefit from early initiation of therapy. Statins should not be reserved until after a patient suffers the catastrophic consequences of atherosclerosis. Contrary to the assertions of the statin opponent, this principle has been demonstrated through reductions in heart attacks, strokes, and mortality in numerous randomized controlled primary-prevention statin trials. Furthermore, data show that once a patient tolerates the initial treatment period, the few side effects that subsequently emerge are largely reversible. Accordingly, every major guidelines committee endorses statin use in secondary prevention and selectively in primary prevention for those with risk factors. The foundation for prevention remains increased physical activity, better dietary habits, and smoking cessation. However, prevention of heart attacks, strokes, and death from cardiovascular disease does not have to be all or none-all statin or all lifestyle. In selected at-risk individuals, the combination of pharmacotherapy and lifestyle changes is more effective than either alone. Future investigation in prevention should focus on improving our ability to identify these at-risk individuals. © 2012 Wiley Periodicals, Inc.

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

    Science.gov (United States)

    Loukovaara, Sirpa; Sahanne, Sari; Takala, Annika; Haukka, Jari

    2018-01-16

    Vitreoretinal (VR) surgery is the third most common intraocular surgery after refractive and cataract surgery. The impact of statin therapy on VR surgery outcomes remains unclear, despite a potentially beneficial effect. We explored the association of preoperative statin therapy and the need for revitrectomy after primary vitrectomy. Our historical, population-based, register-based, VR surgery cohort consisted of 5709 patients operated in a tertiary, academic referral hospital in Finland, during 2008-2014, covering 6.5 years. Subgroup analysis was performed as follows: eyes operated due to (i) rhegmatogenous retinal detachment (RRD), (ii) VR interface diseases (macular pucker/hole), (iii) diabetic maculopathy or proliferative retinopathy, (iv) vitreous haemorrhage, (v) lens subluxation, (vi) vitreous opacities or (vii) other VR indication. The primary end-point event was revitrectomy during a postoperative follow-up period of 1 year due to retinal redetachment, vitreous rehaemorrhage, postoperative endophthalmitis, recurrent pucker or unclosed macular hole. Rhegmatogenous retinal detachment (RRD) was the second most frequent indication of VR surgery, including 1916 patients, with 305 re-operations with rate 0.20 (95% CI 0.18-0.23) per person-year. Statin treatment in time of operation was associated with lower risk of re-operation according to relative scale (incidence rate ratio 0.72, 95% CI 0.53-0.97), but not in absolute scale (incidence rate difference -0.58, 95% CI -4.30 to 3.15 for 100 person-years). No association with statin therapy and vitrectomy outcome was observed in the other VR subgroups. Use of statin treatment was associated with a 28% lower risk of revitrectomy in patients operated due to RRD. Further randomized clinical trials are highly warranted. © 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  13. Who should receive a statin drug to lower cardiovascular risk? Does the drug and the dose of the drug matter?

    Directory of Open Access Journals (Sweden)

    JV (Ian Nixon

    2006-12-01

    Full Text Available JV (Ian NixonDivision of Cardiology, Medical College of Virginia at Virginia Commonwealth University, Richmond VA, USAAbstract: As the numbers of completed outcomes based clinical trials evaluating the use of statin drugs for the management of cardiovascular risk continue to increase, it is clear that the numbers of patients that may benefit from these drugs continues to grow. The recently published studies are reviewed in this summary. The distinction is made between patients requiring either primary or secondary cardiovascular preventive management. The review identifies the increasing numbers of patients who may benefit from the use of statins as primary preventive management, and the changing concepts of the utilization of statin drugs for secondary preventive management, including the more aggressive titration of the drugs to provide incremental improvement in patient outcomes. Available data on the use of statins in the elderly patient are reviewed, and observations are made regarding the intrinsic properties and adverse effects of the drugs. Keywords: cardiovascular risk, statins, elderly patient.

  14. Rising statin use and effect on ischemic stroke outcome

    Directory of Open Access Journals (Sweden)

    Haymore Joseph

    2004-03-01

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

  15. Pleiotropic and Lipid–lowering Effects of Statins in Hypertension

    Science.gov (United States)

    Kamberi, Lulzim Selim; Bedri Bakalli, Aurora; Muhamet Budima, Norma; Rashit Gorani, Daut; Karabulut, Ahmet Muzaffer; Talat Pallaska, Kelmend

    2012-01-01

    Background: Data on the lowering effects of statins in hypertensive patients have been mixed and highly controversial. Some studies shows reductions effects of statins in blood pressure, whereas others do not. The evidence in the literature on the effects of statins on blood pressure raises the possibility that statins may directly lower blood pressure in addition to reduce cholesterol levels–pleiotropic effects of statins. Aim of the study: The role of statins as additional treatment in patients with severe hypertension and advanced aortic atherosclerotic plaques. Methods. We enrolled 62 patients. Study has been approved by Committee of Ethics and patients signed a Term of Free Informed Consent. All patients were studied with transoesophageal echocardiography at baseline and 12 months after enrolment. Inclusion criteria were severe hypertension and presence of aortic atherosclerotic plaques. Patients have been divided into two groups; group A (treated with antihypertenives and statins) and group B (treated, just with antihypertensives). Results: Twenty patients, of totally 38, from group A (20/38 or 52.6%) had significantly plaque reduction. One patient of totally 24 (1/24 or 4.1% ) from group B had significantly atherosclerotic plaque reduction. Difference of plaques reduction between two groups was highly significant. Regarding blood pressure levels, statins users had significantly reduction on systolic and diastolic blood pressure compared to statins nonusers. Conclusion: Hypertensive patients with presence of AA plaques treated with antihypertensives and statins have more BP reduction compared will hypertensive patients treated with antihypertensives alone. PMID:23678313

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

    Science.gov (United States)

    Koskinas, Konstantinos; Wilhelm, Matthias; Windecker, Stephan

    2016-01-01

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

  17. A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation.

    Directory of Open Access Journals (Sweden)

    Evelien van der Meij

    Full Text Available Statins are thought to reduce vascular inflammation through lipid independent mechanisms. Evaluation of such an effect in atherosclerotic disease is complicated by simultaneous effects on lipid metabolism. Abdominal aortic aneurysms (AAA are part of the atherosclerotic spectrum of diseases. Unlike atherosclerotic occlusive disease, AAA is not lipid driven, thus allowing direct evaluation of putative anti-inflammatory effects. The anti-inflammatory potency of increasing doses (0, 20 or 40 mg/day simvastatin or atorvastatin was evaluated in 63 patients that were at least 6 weeks on statin therapy and who underwent open AAA repair. A comprehensive analysis using immunohistochemistry, mRNA and protein analyses was applied on aortic wall samples collected during surgery. The effect of statins on AAA growth was analyzed in a separate prospective study in incorporating 142 patients. Both statins equally effectively and dose-dependently reduced aortic wall expression of NFκB regulated mediators (i.e. IL-6 (P<0.001 and MCP-1 (P<0.001; shifted macrophage polarization towards a M2 phenotype (P<0.0003; selectively reduced macrophage-related markers such as cathepsin K and S (P<0.009 and 0.0027 respectively, and ALOX5 (P<0.0009, and reduced vascular wall NFκB activity (40 mg/day group, P<0.016. No effect was found on other cell types. Evaluation of the clinical efficacy of statins to reduce AAA progression did not indicate an effect of statins on aneurysm growth (P<0.337. Hence, in the context of AAA the clinical relevance of statins pleiotropy appears minimal.

  18. Biomarker evaluation as a potential cause of gender differences in obesity paradox among patients with STEMI.

    Science.gov (United States)

    Baumann, Stefan; Koepp, Johanna; Becher, Tobias; Huseynov, Aydin; Bosch, Katharina; Behnes, Michael; Fastner, Christian; El-Battrawy, Ibrahim; Renker, Matthias; Lang, Siegfried; Weiß, Christel; Borggrefe, Martin; Lehmann, Ralf; Akin, Ibrahim

    2016-03-01

    Obesity with its worldwide growing prevalence is an established cardiovascular risk factor with increased morbidity and mortality. However, the phenomenon, that mild to moderate obesity seems to represent a protective effect on diseases has been termed the "obesity paradox". We retrospectively assessed 529 patients (72.6% male, mean age 59.7±12.7years) admitted with ST-elevation myocardial infarction (STEMI). The female and male study populations were separated into four body mass index (BMI) groups: ≤24.9kg/m(2), 25.0-29.9kg/m(2), 30.0-34.9kg/m(2) and ≥35.0kg/m(2). Blood samples of high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were analyzed. With increasing BMI group the rate of major adverse cardiac events (MACE) decreased in all patients (test for trend p=0.041). No gender difference between MACE and BMI could be noticed (p=0.16). A higher risk for MACE was indicated in group BMI ≤18.5kg/m(2) in comparison to group BMI 25.0-29.9kg/m(2) (OR: 7.93; 95% CI: 1.75-35.89; p=0.0091), whereas group BMI 30.0-34.9kg/m(2) was significant associated with a lower risk in comparison to group BMI 25.0-29.9kg/m(2) (OR: 0.65; 95% CI: 0.21-1.96; p=0.044). An association between HDL-c (p=0.55) or LDL-c (p=0.10) and MACE could not be detected. The study demonstrates that patients with STEMI and a BMI of 30.0-34.9kg/m(2) have a decreased risk for MACE compared to patients with normal BMI. No gender related differences were indicated. An association between MACE and lipoproteins could not be detected. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Statin Induced Myopathy a Patient with Multiple Systemic Diseases

    Directory of Open Access Journals (Sweden)

    Özgül Uçar

    2011-04-01

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

  20. Genome-wide association of lipid-lowering response to statins in combined study populations.

    Directory of Open Access Journals (Sweden)

    Mathew J Barber

    2010-03-01

    Full Text Available Statins effectively lower total and plasma LDL-cholesterol, but the magnitude of decrease varies among individuals. To identify single nucleotide polymorphisms (SNPs contributing to this variation, we performed a combined analysis of genome-wide association (GWA results from three trials of statin efficacy.Bayesian and standard frequentist association analyses were performed on untreated and statin-mediated changes in LDL-cholesterol, total cholesterol, HDL-cholesterol, and triglyceride on a total of 3932 subjects using data from three studies: Cholesterol and Pharmacogenetics (40 mg/day simvastatin, 6 weeks, Pravastatin/Inflammation CRP Evaluation (40 mg/day pravastatin, 24 weeks, and Treating to New Targets (10 mg/day atorvastatin, 8 weeks. Genotype imputation was used to maximize genomic coverage and to combine information across studies. Phenotypes were normalized within each study to account for systematic differences among studies, and fixed-effects combined analysis of the combined sample were performed to detect consistent effects across studies. Two SNP associations were assessed as having posterior probability greater than 50%, indicating that they were more likely than not to be genuinely associated with statin-mediated lipid response. SNP rs8014194, located within the CLMN gene on chromosome 14, was strongly associated with statin-mediated change in total cholesterol with an 84% probability by Bayesian analysis, and a p-value exceeding conventional levels of genome-wide significance by frequentist analysis (P = 1.8 x 10(-8. This SNP was less significantly associated with change in LDL-cholesterol (posterior probability = 0.16, P = 4.0 x 10(-6. Bayesian analysis also assigned a 51% probability that rs4420638, located in APOC1 and near APOE, was associated with change in LDL-cholesterol.Using combined GWA analysis from three clinical trials involving nearly 4,000 individuals treated with simvastatin, pravastatin, or atorvastatin, we

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Atherogenic Dyslipidemia and Residual Cardiovascular Risk in Statin-Treated Patients

    DEFF Research Database (Denmark)

    Sirimarco, Gaia; Labreuche, Julien; Bruckert, Eric

    2014-01-01

    BACKGROUND AND PURPOSE: Treatment with statins reduces the rate of cardiovascular events in high-risk patients, but residual risk persists. At least part of that risk may be attributable to atherogenic dyslipidemia characterized by low high-density lipoprotein cholesterol (≤40 mg/dL) and high......% of subjects in PERFORM and 9% in SPARCL had atherogenic dyslipidemia after ≥3 months on start statin therapy. After a follow-up of 2.3 years (PERFORM) and 4.9 years (SPARCL), a major cardiovascular event occurred in 1123 and 485 patients in the 2 trials, respectively. The risk of major cardiovascular events...... was higher in subjects with versus those without atherogenic dyslipidemia in both PERFORM (hazard ratio, 1.36; 95% confidence interval, 1.14-1.63) and SPARCL (hazard ratio, 1.40; 95% confidence interval, 1.06-1.85). The association was attenuated after multivariable adjustment (hazard ratio, 1.23; 95...

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

    DEFF Research Database (Denmark)

    Brogaard, Hilde Vaiva Tonstad; Køhn, Morten Ganderup; Berget, Oline Sofie

    2012-01-01

    Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time.......Not all patients recovering from acute myocardial infarction (AMI) are optimally treated with statin, and their adherence to statin treatment may be inadequate. We set out to describe changes in statin treatment adherence and cholesterol values over time....

  5. How the functional assessment of culprit and non culprit lesions may improve stratification and treatment of STEMI patients.

    Science.gov (United States)

    Campo, Gianluca; Gallo, Francesco; Bugani, Giulia; Pavasini, Rita; Fineschi, Massimo

    2018-02-01

    Reperfusion therapy of the infarct-related artery (IRA) with primary percutaneous coronary intervention (pPCI) is the cornerstone for the treatment of patients with ST-elevation myocardial infarction (STEMI). However, up to 30% of STEMI patients present a multi-vessel coronary artery disease. Several methods are now available for the assessment of functional severity of a coronary stenosis both for IRA and non culprit coronary lesions. The functional assessment of the IRA has mainly a prognostic implication in terms of major adverse cardiovascular events (MACEs), recovery of left ventricular function and evaluation myocardial viability. Conversely, the functional assessment of the non-culprit coronary lesions has a fundamental role to guide staged revascularization. The aim of this review is to revise the most validated methods to perform the functional assessment of both culprit and non-culprit lesion in ST-elevation myocardial infarction.

  6. Statins attenuate polymethylmethacrylate-mediated monocyte activation.

    LENUS (Irish Health Repository)

    Laing, Alan J

    2012-02-03

    BACKGROUND: Periprosthetic osteolysis precipitates aseptic loosening of components, increases the risk of periprosthetic fracture and, through massive bone loss, complicates revision surgery and ultimately is the primary cause for failure of joint arthroplasty. The anti-inflammatory properties of HMG-CoA reductase inhibitors belonging to the statin family are well recognized. We investigated a possible role for status in initiating the first stage of the osteolytic cycle, namely monocytic activation. METHODS: We used an in vitro model of the human monocyte\\/macrophage inflammatory response to poly-methylmethacrylate (PMMA) particles after pretreat-ing cells with cerivastatin, a potent member of the statin family. Cell activation based upon production of TNF-alpha and MCP-1 cytokines was analyzed and the intracellular Raf-MEK-ERK signal transduction pathway was evaluated using western blot analysis, to identify its role in cell activation and in any cerivastatin effects observed. RESULTS: We found that pretreatment with cerivastatin significantly abrogates the production of inflammatory cytokines TNF-alpha and MCP-1 by human monocytes in response to polymethylmethacrylate particle activation. This inflammatory activation and attenuation appear to be mediated through the intracellular Raf-MEK-ERK pathway. INTERPRETATION: We propose that by intervening at the upstream activation stage, subsequent osteoclast activation and osteolysis can be suppressed. We believe that the anti-inflammatory properties of statins may potentially play a prophylactic role in the setting of aseptic loosening, and in so doing increase implant longevity.

  7. [The combinations of statins and fibrates: pharmacokinetic and clinical implications].

    Science.gov (United States)

    González Santos, Pedro

    2014-07-01

    With mixed dyslipidemia of the atherogenic dyslipidemia type, once the LDL-c objectives have been achieved through statin treatment, there is often a residual risk, for which the addition of a fibrate is recommended. The combination of statins and fibrates has been limited by the possibility of drug interactions, which mostly result in myopathy. Interactions between statins and other drugs are caused by pharmacokinetic mechanisms, mainly by changing the metabolism of statins in the CYP450 enzyme system, in the hepatic glucuronidation pathway or in the transporters responsible for statin distribution in tissues. The most significant adverse eff ect of statins is myopathy, which can also be induced by fibrates and is more frequent when the 2 drugs (statins and fibrates) are combined. This adverse eff ect manifests clinically as myalgia, muscle weakness, increased CK levels and, in its most severe form, rhabdomyolysis. This interaction mainly aff ects gemfibrozil due to its specific action on the CYP450 enzyme system and that interferes with the hepatic glucuronidation of statins by using the same isoenzymes and with organic anion transporters in the liver. When combining statins, we should use other fibric acid derivatives, preferably fenofibrate. Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.

  8. Statin treatment and risk of recurrent venous thromboembolism

    DEFF Research Database (Denmark)

    Nguyen, Cu Dinh; Andersson, Charlotte; Jensen, Thomas Bo

    2013-01-01

    Objectives Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin...... hospitalised VTE (ie, fatal or non-fatal DVT or PE) associated with use of statins. Results 44330 patients with VTE were included in the study. Of these 3914 were receiving statin therapy at baseline. Patients receiving statins were older (6811 compared to 62 +/- 18years), had more comorbidity and used more...... medications. The incidence rate for recurrent VTE was 24.4 (95% CI 22.8 to 26.2) per 1000 person-years among statin users and 48.5 (95% CI 47.4 to 49.7) per 1000 person-years among non-statin users. Statin use was associated with a significantly lower risk of a recurrent VTE, adjusted HR 0.74 (95% CI 0...

  9. Timing and dose of statin therapy define its impact on inflammatory and endothelial responses during myocardial infarction.

    Science.gov (United States)

    Sposito, Andrei C; Santos, Simone N; de Faria, Eliana Cotta; Abdalla, Dulcineia S P; da Silva, Luiza P; Soares, Alexandre A Sousa; Japiassú, André V T; Quinaglia e Silva, Jose C; Ramires, Jose A F; Coelho, Otavio Rizzi

    2011-05-01

    Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. ST-elevation MI patients (n=125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0±4.1 mg/L) and patients treated with 20 (8.5±4.0 mg/L), 40 (3.8±2.5 mg/L), and 80 mg/day (1.4±1.5 mg/L), and the daily differences remained significant until the seventh day (P<0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-α, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P<0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-α, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P<0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P=0.001). This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00906451.

  10. Effect of intracoronary injection of tirofiban combined with anisodamine on myocardial perfusion in patients with STEMI after PCI

    Directory of Open Access Journals (Sweden)

    Xiao-Gang Zhu

    2016-10-01

    Full Text Available Objective: To analyze the effect of intracoronary injection of tirofiban combined with anisodamine on myocardial perfusion in patients with STEMI after PCI. Methods: A total of 78 patients with acute ST segment elevation myocardial infarction (STEMI who received PCI therapy in our hospital were randomly divided into control group and observation group, control group accepted routine PCI treatment, observation group received intracoronary injection of tirofiban and anisodamine in PCI, and myocardial perfusion of two groups was compared. Results: QRS duration values of observation group the instant after PCI and 4h after PCI were less than those of control group (P<0.05; 99mTc-MIBI and 18F-FDG intake of observation group after PCI were more than those of control group (P<0.05; serum MCP-1, sFas, Copeptin, OPN and vWF levels of observation group 4 h after PCI were lower than those of control group (P<0.05. Conclusions: Intracoronary injection of tirofiban combined with anisodamine can optimize myocardial perfusion in patients with STEMI after PCI, and has positive clinical significance.

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-05-30

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

  13. Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans

    Science.gov (United States)

    2011-01-01

    Background To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL) cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods. Methods and Results The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL) cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose. Conclusion We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (re)absorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory) mechanisms. PMID:22018353

  14. Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans

    Directory of Open Access Journals (Sweden)

    Eussen Simone RBM

    2011-10-01

    Full Text Available Abstract Background To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods. Methods and Results The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose. Conclusion We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (reabsorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory mechanisms.

  15. A systems biology strategy reveals biological pathways and plasma biomarker candidates for potentially toxic statin-induced changes in muscle.

    Directory of Open Access Journals (Sweden)

    Reijo Laaksonen

    Full Text Available BACKGROUND: Aggressive lipid lowering with high doses of statins increases the risk of statin-induced myopathy. However, the cellular mechanisms leading to muscle damage are not known and sensitive biomarkers are needed to identify patients at risk of developing statin-induced serious side effects. METHODOLOGY: We performed bioinformatics analysis of whole genome expression profiling of muscle specimens and UPLC/MS based lipidomics analyses of plasma samples obtained in an earlier randomized trial from patients either on high dose simvastatin (80 mg, atorvastatin (40 mg, or placebo. PRINCIPAL FINDINGS: High dose simvastatin treatment resulted in 111 differentially expressed genes (1.5-fold change and p-value<0.05, while expression of only one and five genes was altered in the placebo and atorvastatin groups, respectively. The Gene Set Enrichment Analysis identified several affected pathways (23 gene lists with False Discovery Rate q-value<0.1 in muscle following high dose simvastatin, including eicosanoid synthesis and Phospholipase C pathways. Using lipidomic analysis we identified previously uncharacterized drug-specific changes in the plasma lipid profile despite similar statin-induced changes in plasma LDL-cholesterol. We also found that the plasma lipidomic changes following simvastatin treatment correlate with the muscle expression of the arachidonate 5-lipoxygenase-activating protein. CONCLUSIONS: High dose simvastatin affects multiple metabolic and signaling pathways in skeletal muscle, including the pro-inflammatory pathways. Thus, our results demonstrate that clinically used high statin dosages may lead to unexpected metabolic effects in non-hepatic tissues. The lipidomic profiles may serve as highly sensitive biomarkers of statin-induced metabolic alterations in muscle and may thus allow us to identify patients who should be treated with a lower dose to prevent a possible toxicity.

  16. Lipid Testing and Statin Dosing After Acute Myocardial Infarction.

    Science.gov (United States)

    Wang, William T; Hellkamp, Anne; Doll, Jacob A; Thomas, Laine; Navar, Ann Marie; Fonarow, Gregg C; Julien, Howard M; Peterson, Eric D; Wang, Tracy Y

    2018-01-25

    The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recommend high-intensity statins for patients after myocardial infarction (MI) rather than treating to a low-density lipoprotein cholesterol goal, as the previous ATP III (Adult Treatment Panel third report) guidelines had advised. To evaluate the frequency of postdischarge lipid testing and high-intensity statin use among MI patients discharged on a statin during the ATP III guidelines era, we linked ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry data to Medicare claims for 11 046 MI patients aged ≥65 years who were discharged alive on a statin from 347 hospitals (2007-2009). Multivariable regression was used to evaluate the association between lipid testing and 1-year high-intensity statin use. Only 21% of MI patients were discharged on a high-intensity statin. By 90 days after MI, 44% of patients discharged on a statin underwent lipid testing (43% on low- or moderate-intensity statins and 49% on high-intensity statins; P =0.001). Follow-up lipid testing rates were 47% among patients with in-hospital low-density lipoprotein cholesterol ≥100 mg/dL and 47% among newly prescribed statin recipients. By 1 year, only 14% of patients were on high-intensity statins. Only 4% of patients discharged on low- or moderate-dose statin were uptitrated to high intensity; postdischarge lipid testing was associated with a slightly higher likelihood of high-intensity statin use by 1 year (5.4% versus 2.9%, adjusted odds ratio: 1.92; 95% confidence interval, 1.52-2.41). Previous guidelines recommended low-density lipoprotein cholesterol goal-directed statin therapy, but lipid testing and high-intensity statin use were infrequent after MI. The American College of Cardiology/American Heart Association guidelines may promote more intensive cardiovascular risk reduction by eliminating treatment dependence on lipid testing. © 2018 The Authors. Published on

  17. New insights into mechanisms of statin-associated myotoxicity.

    Science.gov (United States)

    Sirvent, Pascal; Mercier, Jacques; Lacampagne, Alain

    2008-06-01

    Statin drugs represent a major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Besides the tremendous beneficial effects of statins, various forms of muscular toxicity (myalgia, cramp, exercise intolerance, fatigability) occur frequently. Many hypotheses were proposed to explain statin myotoxicity. The goal of this review is to highlight some of the most recent findings that can account for interpreting the pathophysiological mechanisms for statin-induced myotoxicity. Statin-induced myotoxicity appears multifactorial. Apart from the deleterious effect due to a reduction in cholesterol biosynthesis, statins have a direct effect on the respiratory chain of the mitochondria. It is proposed that mitochondrial impairment leads to a mitochondrial calcium leak that directly interferes with the regulation of sarcoplasmic reticulum calcium cycling without excluding a direct effect of statin on the sarcoplasmic reticulum. Both mitochondrial and calcium impairments may account for apoptosis process, oxidative stress, and muscle remodeling and degeneration that have been extensively reported to explain statin myotoxicity and functional symptoms described by treated patients.

  18. [Statins available from chemist shops will not positively affect health

    NARCIS (Netherlands)

    Stalenhoef, A.F.H.

    2007-01-01

    Statins should not become available as over- or behind-the-counter drugs at chemist shops. The efficacy of these drugs when given in low dosages has not been proved although the negative aspect of possible side effects remains a realistic possibility. The use of statins as compensation for an

  19. The risk of cancer in users of statins

    NARCIS (Netherlands)

    Graaf, Matthijs R.; Beiderbeck, Annette B.; Egberts, Antoine C. G.; Richel, Dick J.; Guchelaar, Henk-Jan

    2004-01-01

    Purpose Several preclinical studies suggested a role for 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the treatment of cancer. The objective of this study was to compare the risk of incident cancer between users of statins and users of other cardiovascular medication.

  20. The case for statin therapy in chronic heart failure

    NARCIS (Netherlands)

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

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

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

    Science.gov (United States)

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

    2015-11-02

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

  2. Sympathoinhibitory effect of statins in chronic heart failure.

    NARCIS (Netherlands)

    Gomes, M.E.R.; Lenders, J.W.M.; Bellersen, L.; Verheugt, F.W.A.; Smits, P.; Tack, C.J.J.

    2010-01-01

    OBJECTIVES: Increased (central) sympathetic activity is a key feature of heart failure and associated with worse prognosis. Animal studies suggest that statin therapy can reduce central sympathetic outflow. This study assessed statin effects on (central) sympathetic activity in human chronic heart

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

    Science.gov (United States)

    Thai, Loc Phuoc; Vitry, Agnes Isabelle; Moss, John Robert

    2018-02-01

    Australia, England, France and New Zealand use different policies to regulate their medicines market, which can impact on utilisation and price. To compare the prices and utilisation of statins in Australia, England, France and New Zealand from 2011 to 2013. Utilisation of statins in the four countries was compared using Defined Daily Doses (DDD) per 1000 inhabitants per year. Pairwise Laspeyres and Paasche index comparisons were conducted comparing the price and utilisation of statins. The results showed that the price of statins in New Zealand was the cheapest. The price of statins in Australia was most expensive in 2011 and 2012 but France was more expensive in 2013. There were large differences between the Laspeyres index and Paasche index when comparing the price and utilisation of England with Australia and France. The policies that regulate the New Zealand and England medicines markets were more effective in reducing the price of expensive statins. The relative utilisation of cheaper statins was greatest in England and had a large effect on the differences between the two index results. The pricing policies in Australia have been only partly effective in reducing the price of statins compared to other countries.

  4. Use of statins and the risk of rheumatoid arthritis.

    NARCIS (Netherlands)

    Jong, H. de; Klungel, O.; Dijk, L. van; Vandebriel, R.; Leufkens, H.; Cohen Tervaert, J.W.; Lovenren, H. van

    2009-01-01

    Background: Statins exert immunomodulatory effects which can cause immune-dysregulation and potentially lead to autoimmune reactions. Objectives: To study the association between use of statins and the risk of incident rheumatoid arthritis (RA). Methods: We conducted a case-control study using The

  5. Long-Term Safety and Efficacy of Lowering Low-Density Lipoprotein Cholesterol With Statin Therapy: 20-Year Follow-Up of West of Scotland Coronary Prevention Study.

    Science.gov (United States)

    Ford, Ian; Murray, Heather; McCowan, Colin; Packard, Chris J

    2016-03-15

    Extended follow-up of statin-based low-density lipoprotein cholesterol lowering trials improves the understanding of statin safety and efficacy. Examining cumulative cardiovascular events (total burden of disease) gives a better appreciation of the clinical value of statins. This article evaluates the long-term impact of therapy on mortality and cumulative morbidity in a high-risk cohort of men. The West of Scotland Coronary Prevention Study was a primary prevention trial in 45- to 64-year-old men with high low-density lipoprotein cholesterol. A total of 6595 men were randomized to receive pravastatin 40 mg once daily or placebo for an average of 4.9 years. Subsequent linkage to electronic health records permitted analysis of major incident events over 20 years. Post trial statin use was recorded for 5 years after the trial but not for the last 10 years. Men allocated to pravastatin had reduced all-cause mortality (hazard ratio, 0.87; 95% confidence interval, 0.80-0.94; P=0.0007), attributable mainly to a 21% decrease in cardiovascular death (hazard ratio, 0.79; 95% confidence interval, 0.69-0.90; P=0.0004). There was no difference in noncardiovascular or cancer death rates between groups. Cumulative hospitalization event rates were lower in the statin-treated arm: by 18% for any coronary event (P=0.002), by 24% for myocardial infarction (P=0.01), and by 35% for heart failure (P=0.002). There were no significant differences between groups in hospitalization for noncardiovascular causes. Statin treatment for 5 years was associated with a legacy benefit, with improved survival and a substantial reduction in cardiovascular disease outcomes over a 20-year period, supporting the wider adoption of primary prevention strategies. © 2016 The Authors.

  6. Statin-associated muscle symptoms: position paper from the Luso-Latin American Consortium.

    Science.gov (United States)

    Sposito, Andrei C; Faria Neto, José Rocha; Carvalho, Luiz Sergio F de; Lorenzatti, Alberto; Cafferata, Alberto; Elikir, Gerardo; Esteban, Eduardo; Morales Villegas, Enrique C; Bodanese, Luiz Carlos; Alonso, Rodrigo; Ruiz, Alvaro J; Rocha, Viviane Z; Faludi, André A; Xavier, Hermes T; Coelho, Otávio Rizzi; Assad, Marcelo H V; Izar, Maria C; Santos, Raul D; Fonseca, Francisco A H; Mello E Silva, Alberto; Silva, Pedro Marques da; Bertolami, Marcelo C

    2017-02-01

    In the last two decades, statin therapy has proved to be the most potent isolated therapy for attenuation of cardiovascular risk. Its frequent use has been seen as one of the most important elements for the reduction of cardiovascular mortality in developed countries. However, the recurrent incidence of muscle symptoms in statin users raised the possibility of causal association, leading to a disease entity known as statin associated muscle symptoms (SAMS). Mechanistic studies and clinical trials, specifically designed for the study of SAMS have allowed a deeper understanding of the natural history and accurate incidence. This set of information becomes essential to avoid an unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents overdiagnosis and an inadequate suspension of one of the most powerful prevention strategies of our times. In this context, the Luso-Latin American Consortium gathered all available information on the subject and presents them in detail in this document as the basis for the identification and management of SAMS.

  7. Können Statine den Knochenstoffwechsel positiv beeinflussen?

    Directory of Open Access Journals (Sweden)

    Vock L

    2005-01-01

    Full Text Available Statine, potente Inhibitoren der HMG-CoA-Reduktase, werden erfolgreich zur Senkung der Cholesterinblutspiegel eingesetzt. In den letzten Jahren sind jedoch zahlreiche andere Wirkungen der Statine aufgedeckt worden, die möglicherweise für den Knochenstoffwechsel von Bedeutung sind: In vitro konnten faszinierende knochenanabole Wirkungen der Statine bewiesen werden. Welche molekularen Mechanismen für diese Beobachtungen genau verantwortlich sind, ist nach wie vor unklar. Auch konnten in anderen In-vitro-Studien, Tiermodellen und klinischen Studien diese eindrucksvollen Resultate nicht immer bestätigt werden. Das vorliegende Bild der Statine im Knochenstoffwechsel ist uneinheitlich. Viele Fragen bleiben offen. Es fehlen neben genaueren Erkenntnissen über die Eigenschaften der einzelnen Statine auch Resultate besser auf diese Fragestellung zugeschnittener Studien.

  8. Comparison of coronary arterial lumen dimensions on angiography and plaque characteristics on optical coherence tomography images and their changes induced by statin

    International Nuclear Information System (INIS)

    Dong, Nana; Xie, Zulong; Wang, Wei; Dai, Jiannan; Sun, Meng; Pu, Zhongyue; Tian, Jinwei; Yu, Bo

    2016-01-01

    Coronary angiography (CAG) is widely used to assess lumen dimensions, and optical coherence tomography (OCT) is used to evaluate the characteristics of atherosclerotic plaque. This study was aimed to compare coronary lumen dimensions using CAG and plaque characteristics using OCT and their changes during statin therapy. We identified 97 lipid-rich plaques from 69 statin-naïve patients, who received statin therapy in the following 12 months. CAG and OCT examinations were conducted at baseline and 12-month follow-up period. Lesion length, as measured by CAG, was closely correlated with lipid length by OCT (baseline: r = 0.754, p < 0.001; follow-up: r = 0.639, p < 0.001). However, no significant correlations were found between the other findings on OCT and data on CAG. With 12-month statin therapy, microstructures of lipid-rich plaques were significantly improved, but CAG-derived lumen dimensions were not improved. Moreover, we found no significant relationship between changes in OCT measurements and changes in CAG data over time. Lipid length on OCT and lesion length on CAG were closely correlated. However, plaque microstructural characteristics on OCT showed no significantly statistically correlations with lumen dimensions on CAG, neither did their evolutionary changes induced by statin over time. Clinical trial registry: ClinicalTrial.gov. Registered number: NCT01023607. Registered 1 December 2009

  9. Pre-hospital alarm activation for STEMI patients undergoing primary percutaneous coronary intervention in the era of transradial procedures.

    Science.gov (United States)

    Rigamonti, Fabio; Gencer, Baris; Rey, Florian; Chaara, Jawad; Tessitore, Elena; Bunwaree, Sholan; Meier, Pascal; Noble, Stéphane; Grosgurin, Olivier; Larribau, Robert; Windecker, Stephan; Carbone, Federico; Montecucco, Fabrizio; Rodondi, Nicolas; Matter, Christian M; Luscher, Thomas F; Mach, François; Roffi, Marco

    2016-11-01

    Transradial access (TRA) improves outcome compared with trans-femoral access for the management of patients with acute coronary syndromes. In this setting, it is unknown whether the activation of a pre-hospital alarm system (PHAS) confers additional benefit for the prognosis of patients with ST-segment elevation myocardial infarction (STEMI). We retrospectively analyzed a cohort of patients with a first STEMI who underwent a primary percutaneous coronary intervention (PPCI) at a single center within a prospective cohort of acute coronary syndrome patients (SPUM-ACS). TRA was used in 85% of patients. We assessed how PHAS (n=165) vs. no-PHAS (n=166) activation was associated with the composite outcome of all-cause mortality and recurrence of myocardial infarction (MI) at 1-year follow-up. As secondary outcomes, the individual clinical endpoints were separately assessed for association. Compared with no-PHAS patients, patients in the PHAS group were predominantly women, and presented more frequently with dyslipidemia and cardiac arrest. A significant reduction in the composite outcome of all-cause mortality and recurrent MI at 1-year was observed in the PHAS group, compared with no-PHAS (3.6% vs. 8.5%, p=0.027). When adjusted for age, sex and resuscitation status, PHAS activation remained associated with decreased all-cause mortality and recurrent MI (HR: 0.36 [95% CI: 0.13-0.95]; p=0.040). This study suggests that the benefit of PHAS activation in STEMI patients undergoing PPCI persists also in the era of TRA. Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  10. Clinical Significance of Reciprocal ST-Segment Changes in Patients With STEMI: A Cardiac Magnetic Resonance Imaging Study.

    Science.gov (United States)

    Hwang, Ji-Won; Yang, Jeong Hoon; Song, Young Bin; Park, Taek Kyu; Lee, Joo Myung; Kim, Ji-Hwan; Jang, Woo Jin; Choi, Seung-Hyuk; Hahn, Joo-Yong; Choi, Jin-Ho; Ahn, Joonghyun; Carriere, Keumhee; Lee, Sang Hoon; Gwon, Hyeon-Cheol

    2018-02-22

    We sought to determine the association of reciprocal change in the ST-segment with myocardial injury assessed by cardiac magnetic resonance (CMR) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). We performed CMR imaging in 244 patients who underwent primary PCI for their first STEMI; CMR was performed a median 3 days after primary PCI. The first electrocardiogram was analyzed, and patients were stratified according to the presence of reciprocal change. The primary outcome was infarct size measured by CMR. Secondary outcomes were area at risk and myocardial salvage index. Patients with reciprocal change (n=133, 54.5%) had a lower incidence of anterior infarction (27.8% vs 71.2%, P < .001) and shorter symptom onset to balloon time (221.5±169.8 vs 289.7±337.3min, P=.042). Using a multiple linear regression model, we found that patients with reciprocal change had a larger area at risk (P=.002) and a greater myocardial salvage index (P=.04) than patients without reciprocal change. Consequently, myocardial infarct size was not significantly different between the 2 groups (P=.14). The rate of major adverse cardiovascular events, including all-cause death, myocardial infarction, and repeat coronary revascularization, was similar between the 2 groups after 2 years of follow-up (P=.92). Reciprocal ST-segment change was associated with larger extent of ischemic myocardium at risk and more myocardial salvage but not with final infarct size or adverse clinical outcomes in STEMI patients undergoing primary PCI. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  11. The Effect of Statins on Blood Gene Expression in COPD.

    Directory of Open Access Journals (Sweden)

    Ma'en Obeidat

    Full Text Available COPD is currently the fourth leading cause of death worldwide. Statins are lipid lowering agents with documented cardiovascular benefits. Observational studies have shown that statins may have a beneficial role in COPD. The impact of statins on blood gene expression from COPD patients is largely unknown.Identify blood gene signature associated with statin use in COPD patients, and the pathways underpinning this signature that could explain any potential benefits in COPD.Whole blood gene expression was measured on 168 statin users and 451 non-users from the ECLIPSE study using the Affymetrix Human Gene 1.1 ST microarray chips. Factor Analysis for Robust Microarray Summarization (FARMS was used to process the expression data. Differential gene expression analysis was undertaken using the Linear Models for Microarray data (Limma package adjusting for propensity score and surrogate variables. Similarity of the expression signal with published gene expression profiles was performed in ProfileChaser.25 genes were differentially expressed between statin users and non-users at an FDR of 10%, including LDLR, CXCR2, SC4MOL, FAM108A1, IFI35, FRYL, ABCG1, MYLIP, and DHCR24. The 25 genes were significantly enriched in cholesterol homeostasis and metabolism pathways. The resulting gene signature showed correlation with Huntington's disease, Parkinson's disease and acute myeloid leukemia gene signatures.The blood gene signature of statins' use in COPD patients was enriched in cholesterol homeostasis pathways. Further studies are needed to delineate the role of these pathways in lung biology.

  12. Statin treatment is associated with reduced toll-like receptor 4 immunohistochemical expression on carotid atherosclerotic plaques: a novel effect of statins.

    Science.gov (United States)

    Katsargyris, Athanasios; Klonaris, Chris; Tsiodras, Sotirios; Bastounis, Elias; Giannopoulos, Athanasios; Theocharis, Stamatios

    2011-12-01

    Toll-like receptor 4 (TLR4) has been recently implicated in inflammatory pathways involved in carotid plaque destabilization. Given that statins have plaque stabilization and inflammation reduction effects, we investigated whether TLR4 expression on carotid atherosclerotic plaques correlates with statin intake. Carotid atherosclerotic plaques were obtained on 140 patients (preoperative statin intake, n = 70). TLR4 immunohistochemical expression was investigated in endothelial cells (ECs), macrophages (MACs) and smooth muscle cells (SMCs) of carotid atheroma. TLR4 positivity, over-expression and intensity of immunostaining were compared in statin versus no-statin users. The results of this study showed that statin users had a significantly lower expression of TLR4 in ECs (P = 0.02, 0.001, 0.006 for TLR4 positivity, increased intensity and over-expression, respectively). Similarly, TLR4 positivity was less pronounced in carotid plaque MACs of statin users (P = 0.03). No carotid specimen with increased EC TLR4 intensity or over-expression was observed among statin users. The prevalence of any cerebrovascular accident was 61.4% in the 'no statin' versus 18.6% in the 'statin' group (odds ratio for statin use: 0.14, 95% CI: 0.07-0.31, P < 0.001). In conclusion, statin treatment is associated with attenuated TLR4 expression on human carotid atherosclerotic plaques and a reduced risk of carotid-related cerebrovascular events. TLR4 may potentially mediate statins' plaque stabilization effects. Further investigation is necessary.

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

    Science.gov (United States)

    Zechmeister, Carrie; Hurren, Jeff; McNorton, Kelly

    2015-07-01

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

  14. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    Energy Technology Data Exchange (ETDEWEB)

    Alizadeh, Moein [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Sylvestre, Marie-Pierre [Research Center, Department of Statistics, University of Montreal, Montreal, Quebec (Canada); Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Taussky, Daniel, E-mail: daniel.taussky.chum@ssss.gouv.qc.ca [Department of Radiation Oncology, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada)

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

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

    Directory of Open Access Journals (Sweden)

    Stephen Caldwell

    2017-06-01

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

  16. Efficacy of Combination Therapy of Statin and Vitamin C in Comparison with Statin in the Prevention of Post-CABG Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Jahanbakhsh Samadikhah

    2014-03-01

    Full Text Available Purpose: Atrial fibrillation (AF is the most frequent arrhythmia that follows coronary artery bypass graft (CABG. Patients developing postoperative AF (POAF have significantly higher mortality rates. The consistent prophylactic effectiveness of statins and vitamin C are well-accepted; however, no evaluation on combined therapy has been performed. We aimed at assessing the efficacy of combination therapy with statin and vitamin C in comparison with statin alone in the prevention of post CABG-AF. Methods: In a randomized double blind clinical trial, 120 candidates of CABG were recruited in Tabriz Madani Educational Center in a 15-month period of time. Patients were randomized into two groups of 60 receiving oral atorvastatin (40mg plus oral vitamin C (2g/d operation day and 1g/d for five consequent days for intervention group and oral atorvastatin (40mg for control group. Occurrence of post CABG AF was compared between the two groups. Results: There were 60 patients, 43 males and 17 females with a mean age of 61.0±11.5 (29-78 years, in the intervention group and sixty patients, 39 males and 21 females with a mean age of 60.5±11.3 (39-81 years, in the control group. The post CABG AF occurred in 6 cases (10% in the interventional group and 15 patients (25% in the controls (P=0.03, odds ratio=0.33, 95% confidence interval 0.12-0.93. Conclusion: Based on our findings, combination prophylaxis against post CABG AF with oral atorvastatin plus vitamin C is significantly more effective than single oral atorvastatin.

  17. Efficacy of Combination Therapy of Statin and Vitamin C in Comparison with Statin in the Prevention of Post-CABG Atrial Fibrillation

    Science.gov (United States)

    Samadikhah, Jahanbakhsh; Golzari, Samad EJ; Sabermarouf, Babak; karimzadeh, Ida; Tizro, Parastou; Mohammad Khanli, Hadi; Ghabili, Kamyar

    2014-01-01

    Purpose: Atrial fibrillation (AF) is the most frequent arrhythmia that follows coronary artery bypass graft (CABG). Patients developing postoperative AF (POAF) have significantly higher mortality rates. The consistent prophylactic effectiveness of statins and vitamin C are well-accepted; however, no evaluation on combined therapy has been performed. We aimed at assessing the efficacy of combination therapy with statin and vitamin C in comparison with statin alone in the prevention of post CABG-AF. Methods: In a randomized double blind clinical trial, 120 candidates of CABG were recruited in Tabriz Madani Educational Center in a 15-month period of time. Patients were randomized into two groups of 60 receiving oral atorvastatin (40mg) plus oral vitamin C (2g/d operation day and 1g/d for five consequent days) for intervention group and oral atorvastatin (40mg) for control group. Occurrence of post CABG AF was compared between the two groups. Results: There were 60 patients, 43 males and 17 females with a mean age of 61.0±11.5 (29-78) years, in the intervention group and sixty patients, 39 males and 21 females with a mean age of 60.5±11.3 (39-81) years, in the control group. The post CABG AF occurred in 6 cases (10%) in the interventional group and 15 patients (25%) in the controls (P=0.03, odds ratio=0.33, 95% confidence interval 0.12-0.93). Conclusion: Based on our findings, combination prophylaxis against post CABG AF with oral atorvastatin plus vitamin C is significantly more effective than single oral atorvastatin. PMID:24409416

  18. Pleiotropic effects of statins in the perioperative setting

    Directory of Open Access Journals (Sweden)

    George Galyfos

    2017-01-01

    Full Text Available Statins belong to a specific group of drugs that have been described for their ability to control hyperlipidemia as well as for other pleiotropic effects such as improving vascular endothelial function, inhibition of oxidative stress pathways, and anti-inflammatory actions. Accumulating clinical evidence strongly suggests that statins also have a beneficial effect on perioperative morbidity and mortality. Therefore, this review aims to present all recent and pooled data on statin treatment in the perioperative setting as well as to highlight considerations regarding their indications and therapeutic application.

  19. [Statin-associated muscle symptoms : Current management in 2018].

    Science.gov (United States)

    Kosinski, Christophe; Tran, Christel; Kuntzer, Thierry; Rodondi, Nicolas; Collet, Tinh-Hai

    2018-02-28

    Statins are the first line treatment in hyperlipidemia, either in primary or secondary prevention of cardiovascular diseases. One of the most prescribed drug class worldwide, this drug class is often the focus of highly publicized drug controversies. Various adverse effects have been attributed to statins, in particular statin-associated muscle symptoms (SAMS). This condition varies in severity (from frequent isolated myalgia to rare severe myositis, even rhabdomyolysis) and often leads to treatment termination. Because SAMS are a daily challenge in clinical practice, we review here the recent medical literature on this topic and suggest a management strategy to be shared with the patient as an active partner.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  1. [Dyslipemia in diabetics treated with statins. Results of the DYSIS study in Spian].

    Science.gov (United States)

    Millán, Jesús; Alegría, Eduardo; Guijarro, Carlos; Lozano, Jose V; Vitale, Gustavo C; González-Timón, Belén; González-Juanatey, José R

    2013-11-16

    Type 2 diabetes mellitus (DM2) is characterized by carrying a high cardiovascular risk. This situation underscores the importance of intensively treating the risk factors present in diabetic patients, notably dyslipemia. The treatment with cholesterol-lowering drugs may be especially effective to reduce the cardiovascular risk in diabetic patients. Therefore, LDL-cholesterol is a priority target in the lipid management of these patients. This study analyzes the alterations in the lipid profile of diabetic patients receiving treatment with statins, which therefore may contribute to persistent cardiovascular risk in such individuals. The DYSIS (Dyslipidemia International Study) is an international, observational trial analyzing the lipid profile of patients treated with statins and followed-up on in outpatient clinics by primary care physicians and specialists. This study is referred to the data on the diabetic patients. Of the total patients enrolled in the DYSIS, the present study included 3703 patients, 39% being diabetics. A total of 59.2% of diabetics showed LDL-C out of goal; triglyceride elevation was observed in 43.6% and 36.4% showed low HDL-C. In diabetics patients with coronary heart disease, 31% had uncontrolled levels of all three lipid parameters. The prevalence of out of goal LDL-C in diabetic patients with metabolic syndrome was close to 60%; 39.8% had low levels of HDL-C and 46,6% high levels of triglycerides. In addition, 57% of diabetic patients with obesity showed LDL-C out of control, despite statins treatment. Cardiovascular diseases remain the main cause of morbidity-mortality in patients with DM2. The results of the present study show that in diabetic patients the degree of control is very limited with regard to LDL-cholesterol. More than half of diabetic patients treated with statins had LDL-cholesterol out of goal. The level of dyslipidemia control was low, despite statins treatment. Therefore, the detection of atherogenic dyslipidemia may

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

    LENUS (Irish Health Repository)

    Horgan, S

    2012-02-01

    BACKGROUND: Statins are proven to reduce cardiovascular risk; however, substantial risk remains in patients on statin therapy. Persisting dyslipidaemia is likely to play a contributory role. AIM: To assess the prevalence of persisting lipid abnormalities in patients treated with statins. METHODS: DYSIS was a cross-sectional study of 22,063 patients in Europe and Canada. 900 Irish patients participated. All patients were >\\/= 45 years and treated with statins for >\\/= 3 months. Data were collected from the patients\\' records. ESC guidelines were used to classify risk and to define lipid levels. RESULTS: Mean age was 66.1 years with women representing 40.7%. 78.6% were high-risk patients; that is 53.9% with cardiovascular disease (CVD), 20.1% with diabetes and 15.9% with a SCORE risk >\\/= 5%. Total cholesterol was not at goal in 34.4% of all patients. LDL-C was elevated in 30.8% of all patients and in 30% at high risk. Low HDL-C was found in 34.7% of high-risk patients compared to 16.9% of patients with an ESC score <5%. In diabetics without CVD, low HDL-C and elevated TGs were found in 46 and 44.3%, respectively. CONCLUSIONS: Despite statin therapy, a significant number of patients have persistent dyslipidaemia. While LDL-C targets are suboptimal in three out of ten patients, the prevalence of low HDL-C and high TGs in high-risk patients is greater than one in three. A more integrated approach to the treatment of patients with dyslipidaemia is warranted. Clinical trials are needed to assess the impact of therapies that raise HDL-C and lower elevated TGs.

  3. Statin use and survival outcomes in endocrine-related gynecologic cancers: A systematic review and meta-analysis.

    Science.gov (United States)

    Xie, Weimin; Ning, Li; Huang, Yuenan; Liu, Yan; Zhang, Wen; Hu, Yingchao; Lang, Jinghe; Yang, Jiaxin

    2017-06-20

    Previous studies investigating the association between statin use and survival outcomes in gynecologic cancers have yielded controversial results. We conducted a systematic review and meta-analysis to evaluate the association based on available evidence. We searched the databases of the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and PubMed from inception to January 2017. Studies that evaluated the association between statin use and survival outcomes in gynecologic cancers were included. Pooled hazard ratios (HRs) for overall survival, disease-specific survival and progression-free survival were calculated using a fixed-effects model. A total of 11 studies involving more than 6,920 patients with endocrine-related gynecologic cancers were identified. In a meta-analysis of 7 studies involving 5,449 patients with endocrine-related gynecologic cancers, statin use was linked to improved overall survival (HR, 0.71; 95% confidence interval [CI], 0.63 to 0.80) without significant heterogeneity (I2 = 33.3%). Statin users also had improved disease-specific survival (3 studies, HR, 0.72; 95% CI, 0.58 to 0.90, I2 = 35.1%) and progression-free survival (3 studies, HR, 0.68; 95% CI, 0.49 to 0.93, I2 = 33.6%) in endocrine-related gynecologic cancers. Our findings support that statin use has potential survival benefits for patients with endocrine-related gynecologic cancers. Further large-scale prospective studies are required to validate our findings.

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

    Science.gov (United States)

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

    2015-01-27

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

  5. Effect of rhBNP on renal function in STEMI-HF patients with mild renal insufficiency undergoing primary PCI.

    Science.gov (United States)

    Xing, Kun; Fu, Xianghua; Wang, Yanbo; Li, Wei; Gu, Xinshun; Hao, Guozhen; Miao, Qing; Li, Shiqiang; Jiang, Yunfa; Fan, Weize; Geng, Wei

    2016-04-01

    This study aims to investigate the effect of recombinant human brain natriuretic peptide (rhBNP) on renal function and contrast-induced nephropathy (CIN) incidence in ST-segment elevation myocardial infarction and heart failure (STEMI-HF) patients with mild renal insufficiency undergoing primary percutaneous coronary intervention (PCI). A total of 116 participants were randomized into rhBNP (rhBNP, n = 57) and nitroglycerin group (NIT, n = 59), receiving intravenous rhBNP or nitroglycerin from admission to 72 h after PCI. Renal function was assessed by serum creatinine (SCr), estimated glomerular filtration rate (eGFR), Cystatin-C (Cys-C) and β2-microglobulin before and after primary PCI, and calculated the incidence of CIN within 72 h after PCI. There were no significant differences in SCr, eGFR and β2-microglobulin between the two groups (P > 0.05, respectively). Compared with the NIT group, the total urinary volume within 72 h was higher while the level of Cys-C at 24 and 72 h after PCI was lower in the rhBNP group. rhBNP was associated with a decline in the incidence of CIN (12.28 vs. 28.81 %, P renal injury was not different between rhBNP and nitroglycerin in STEMI-HF patients with mild renal insufficiency. However, infusion of rhBNP was associated with a decline in incidence of CIN.

  6. Lipid-lowering effects of statins

    International Nuclear Information System (INIS)

    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

  7. Statin use and reduced cancer-related mortality

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Nordestgaard, Børge G; Bojesen, Stig E

    2012-01-01

    A reduction in the availability of cholesterol may limit the cellular proliferation required for cancer growth and metastasis. We tested the hypothesis that statin use begun before a cancer diagnosis is associated with reduced cancer-related mortality....

  8. Statin Side Effects: Weigh the Benefits and Risks

    Science.gov (United States)

    ... yellowing of your skin or eyes. Increased blood sugar or type 2 diabetes It's possible your blood ... high-blood-cholesterol/in-depth/statin-side-effects/ART-20046013 . Mayo Clinic Footer Legal Conditions and Terms ...

  9. Rhabdomyolysis induced by a single dose of a statin

    OpenAIRE

    Jamil, S; Iqbal, P

    2004-01-01

    Statins have been shown to cause myotoxicity and rhabdomyolysis. In most cases rhabdomyolysis occurs following the use of these drugs for at least one week. A case of rhabdomyolysis after just a single dose of simvastatin is reported.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    Statin therapy is an important secondary prevention measure in cardiovascular disease. However, the side effects associated with statin use could potentially affect patients' quality of life. Little is known about the influence of statin therapy on the well-being and health status of cardiac...... multivariate analysis of variance. Of the 409 patients, 60% were prescribed statins. Statin use was independently associated with poorer role limitations-physical (p = 0.001), social functioning (p = 0.007), and role limitations-emotional (p = 0.006) during the 12 months after implantation, independent...... of statin type, dosage, and other potential confounders. The associations between statin therapy and depression (p = 0.06) and statin therapy and physical functioning (p = 0.05) were borderline significant, and no association was found with anxiety (p >0.05). In conclusion, statin therapy was associated...

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

    Science.gov (United States)

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

    2011-01-01

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

  12. Adverse side effects of statins in the oral cavity.

    Science.gov (United States)

    Pascual Cruz, Montserrat; Chimenos Küstner, Eduardo; García Vicente, José António; Mezquiriz Ferrero, Xavier; Borrell Thio, Eulalia; López López, José

    2008-02-01

    Increased plasma levels of cholesterol are high risk factors of cardiovascular disease. Statins are drugs that inhibit cholesterol synthesis at both pancreatic and extrahepathic levels, being the treatment of choice for hypercholesterolemia. To analyze the side effects of statins in the mouth cavity, and to analyze the symptoms after interruption of the treatment. Observational study, preliminary. Patients aged 50-70, diagnosed with hypercholesterolemia and undergoing treatment with statins, referred from their primary care physician to the dentist's office. Anamnesis over oral symptoms was performed in the first visit. Statin treatment was discontinued, followed by lab tests and control visits seven and fifteen days later. We monitored the improvement and/or remission of oral symptoms. Statin treatment was resumed, sending out a report of the patient evolution to the PCP. Symptoms were registered in sheet specially designed for the study. patient refusal, use of drugs for dry mouth treatment, Sjögren's syndrome. n=26 patients. Dry mouth patients: improvement in 17 out of 23 patients (88.5%). Itchiness: 6 out of 15 cases improved (57.7%). Bitterness: improvement in 13 out of 14 patients (53.8%). Cough: improvement in 11 out of 12 patients (46.1%). A high percentage of oral symptoms are associated to treatment with statins. There is a marked improvement after temporary interruption of the treatment. Little is known regarding the side effects of oral treatment with statins. This preliminary study includes a relatively small number of patients. The design of experimental treatments will be required to establish a true correlation between statin treatment and oral symptoms.

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Science.gov (United States)

    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.

  15. Pleiotropic Effects of Statins on the Cardiovascular System.

    Science.gov (United States)

    Oesterle, Adam; Laufs, Ulrich; Liao, James K

    2017-01-06

    The statins have been used for 30 years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol. Statins may exert cardiovascular protective effects that are independent of LDL-cholesterol lowering called pleiotropic effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small GTP-binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of proinflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis. The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matter of debate and are hard to quantify because the degree of isoprenoid inhibition by statins correlates to some extent with the amount of LDL-cholesterol reduction. This review examines some of the currently proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any clinical relevance in cardiovascular disease. © 2017 American Heart Association, Inc.

  16. Neuroprotective effects of statins against amyloid β-induced neurotoxicity

    Directory of Open Access Journals (Sweden)

    Hsin-Hua Li

    2018-01-01

    Full Text Available A growing body of evidence suggests that disruption of the homeostasis of lipid metabolism affects the pathogenesis of Alzheimer's disease (AD. In particular, dysregulation of cholesterol homeostasis in the brain has been reported to considerably increase the risk of developing AD. Thus, dysregulation of lipid homeostasis may increase the amyloid β (Aβ levels by affecting amyloid precursor protein (APP cleavage, which is the most important risk factor involved in the pathogenesis of AD. Previous research demonstrated that Aβ can trigger neuronal insulin resistance, which plays an important role in response to Aβ-induced neurotoxicity in AD. Epidemiological studies also suggested that statin use is associated with a decreased incidence of AD. Therefore, statins are believed to be a good candidate for conferring neuroprotective effects against AD. Statins may play a beneficial role in reducing Aβ-induced neurotoxicity. Their effect involves a putative mechanism beyond its cholesterol-lowering effects in preventing Aβ-induced neurotoxicity. However, the underlying molecular mechanisms of the protective effect of statins have not been clearly determined in Aβ-induced neurotoxicity. Given that statins may provide benefits beyond the inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase, these drugs may also improve the brain. Thus, statins may have beneficial effects on impaired insulin signaling by activating AMP-activated protein kinase (AMPK in neuronal cells. They play a potential therapeutic role in targeting Aβ-mediated neurotoxicity.

  17. Effects of rosuvastatin on progression of stenosis in adult patients with congenital aortic stenosis (PROCAS Trial)

    NARCIS (Netherlands)

    Linde, D. van der; Yap, S.C.; Dijk, A.P. van; Budts, W.; Pieper, P.G.; Burgh, P.H. van der; Mulder, B.J.; Witsenburg, M.; Cuypers, J.A.; Lindemans, J.; Takkenberg, J.J.; Roos-Hesselink, J.W.

    2011-01-01

    Recent trials have failed to show that statin therapy halts the progression of calcific aortic stenosis (AS). We hypothesized that statin therapy in younger patients with congenital AS would be more beneficial, because the valve is less calcified. In the present double-blind, placebo-controlled

  18. Understanding the Effect of Statins and Patient Adherence in Atherosclerosis via a Quantitative Systems Pharmacology Model Using a Novel, Hybrid, and Multi-Scale Approach

    Directory of Open Access Journals (Sweden)

    Cesar Pichardo-Almarza

    2017-09-01

    Full Text Available Background and Objective: Statins are one of the most prescribed drugs to treat atherosclerosis. They inhibit the hepatic HMG-CoA reductase, causing a reduction of circulating cholesterol and LDL levels. Statins have had undeniable success; however, the benefits of statin therapy crystallize only if patients adhere to the prescribed treatment, which is far away from reality since adherence decreases with time with around half of patients discontinue statin therapy within the first year. The objective of this work is to; firstly, demonstrate a formal in-silico methodology based on a hybrid, multiscale mathematical model used to study the effect of statin treatment on atherosclerosis under different patient scenarios, including cases where the influence of medication adherence is examined and secondly, to propose a flexible simulation framework that allows extensions or simplifications, allowing the possibility to design other complex simulation strategies, both interesting features for software development.Methods: Different mathematical modeling paradigms are used to present the relevant dynamic behavior observed in biological/physiological data and clinical trials. A combination of continuous and discrete event models are coupled to simulate the pharmacokinetics (PK of statins, their pharmacodynamic (PD effect on lipoproteins levels (e.g., LDL and relevant inflammatory pathways whilst simultaneously studying the dynamic effect of flow-related variables on atherosclerosis progression.Results: Different scenarios were tested showing the impact of: (1 patient variability: a virtual population shows differences in plaque growth for different individuals could be as high as 100%; (2 statin effect on atherosclerosis: it is shown how a patient with a 1-year statin treatment will reduce his plaque growth by 2–3% in a 2-year period; (3 medical adherence: we show that a patient missing 10% of the total number of doses could increase the plaque growth

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

    Science.gov (United States)

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

    2015-04-01

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

  20. Pre-hospital diagnosis and transfer of patients with acute myocardial infarction—a decade long experience from one of Europe's largest STEMI networks

    DEFF Research Database (Denmark)

    Clemmensen, Peter; Schoos, Mikkel Malby; Lindholm, Matias Greve

    2013-01-01

    Early reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) is essential. Although primary percutaneous coronary intervention (pPCI) is the preferred revascularization technique, it often involves longer primary transportation or secondary inter-hospital transfers and th...

  1. The impact of systems-of-care on pharmacoinvasive management with streptokinase: The subgroup analysis of the TN-STEMI programme

    Directory of Open Access Journals (Sweden)

    Deep Chandh Raja

    2017-09-01

    Conclusion: The implementation of a system-of-care (hub-and-spoke model in the pharmacoinvasive group of the TN-STEMI programme demonstrated shorter lysis-to-angiogram times, better TIMI flow patterns and lower thrombus burden in the post-implementation phase.

  2. A Case of Statin-Associated Autoimmune Myopathy

    Directory of Open Access Journals (Sweden)

    Alexander J Sweidan

    2017-03-01

    Full Text Available A 70-year-old previously independent man developed progressive proximal leg weakness resulting in a fall at home suffering traumatic brain injury. He was prescribed a statin medication two years prior, but this was discontinued on admission to the hospital due to concern for statin myopathy. His weakness continued to progress while in acute rehabilitation, along with the development of dysphagia requiring placement of gastrostomy tube and respiratory failure requiring tracheostomy. Corticosteroids and intravenous immunoglobulin were administered without response. Nerve conduction study demonstrated no evidence of neuropathy; electromyography revealed spontaneous activity suggestive of myopathy. A muscle biopsy was performed and demonstrated myonecrosis. Serology was positive for autoantibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR, verifying our diagnosis of statin-associated autoimmune myopathy (SAM. The patient was subsequently treated with rituximab and methotrexate and demonstrated mild clinical improvement. He was eventually liberated from the ventilator. However, later in the course of treatment, he developed respiratory distress and required ventilator support. The patient was discharged to long-term acute care two months after his initial presentation and died due to ventilator-acquired pneumonia three months later. Since their introduction 30 years ago, statin medications have been widely prescribed to prevent cardiovascular diseases. Myalgias and/or myopathic symptoms are among the most recognized side effects of the medication. Statin-associated autoimmune myopathy is a very rare complication of statin use and estimated to affect two to three for every 100,000 patients treated. Clinically, the condition presents as progressive symmetric weakness, muscle enzyme elevations, necrotizing myopathy on muscle biopsy, and the presence of autoantibodies to HMGCR. These findings will often persist and even progress despite

  3. Statin Therapy and Risk of Acute Memory Impairment.

    Science.gov (United States)

    Strom, Brian L; Schinnar, Rita; Karlawish, Jason; Hennessy, Sean; Teal, Valerie; Bilker, Warren B

    2015-08-01

    Reports on the association between statins and memory impairment are inconsistent. To assess whether statin users show acute decline in memory compared with nonusers and with users of nonstatin lipid-lowering drugs (LLDs). Using The Health Improvement Network database during January 13, 1987, through December 16, 2013, a retrospective cohort study compared 482,543 statin users with 2 control groups: 482,543 matched nonusers of any LLDs and all 26,484 users of nonstatin LLDs. A case-crossover study of 68,028 patients with incident acute memory loss evaluated exposure to statins during the period immediately before the outcome vs 3 earlier periods. Analysis was conducted from July 7, 2013, through January 15, 2015. When compared with matched nonusers of any LLDs (using odds ratio [95% CI]), a strong association was present between first exposure to statins and incident acute memory loss diagnosed within 30 days immediately following exposure (fully adjusted, 4.40; 3.01-6.41). This association was not reproduced in the comparison of statins vs nonstatin LLDs (fully adjusted, 1.03; 0.63-1.66) but was also present when comparing nonstatin LLDs with matched nonuser controls (adjusted, 3.60; 1.34-9.70). The case-crossover analysis showed little association. Both statin and nonstatin LLDs were strongly associated with acute memory loss in the first 30 days following exposure in users compared with nonusers but not when compared with each other. Thus, either all LLDs cause acute memory loss regardless of drug class or the association is the result of detection bias rather than a causal association.

  4. Cost-effectiveness of radial vs. femoral approach in primary percutaneous coronary intervention in STEMI – Randomized, control trial

    Directory of Open Access Journals (Sweden)

    Łukasz Kołtowski

    2016-05-01

    Conclusions: The total in-hospital costs were similar between the study groups. The indirect costs were lower in the radial group. Introduction of radial access as the default approach in all centers may significantly reduce the overall financial burden from a social perspective.

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

    Science.gov (United States)

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

    2015-01-01

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

  6. Effect of erythropoietin combined with interventional therapy on cardiac function injury and inflammation in patients with STEMI

    Directory of Open Access Journals (Sweden)

    You-Gen Zhou

    2017-04-01

    Full Text Available Objective: To explore the effect of erythropoietin combined with interventional therapy on cardiac function injury and inflammation in patients with STEMI. Methods: 58 patients with STEMI treated in our hospital between April 2012 and September 2015 were selected, the treatment methods and test results were reviewed, and then they were divided into the control group who accepted interventional therapy alone and the observation group who accepted erythropoietin combined with interventional therapy. Before and after treatment, color Doppler diasonograph was used to detect cardiac function parameters; immune scatter turbidimetry was used to determine myocardial injury marker levels in peripheral blood; ELISA was used to detect serum inflammatory factor levels. Results: Before treatment, differences in cardiac function parameter levels, myocardial injury marker contents and inflammatory factor contents were not statistically significant between two groups of patients (P>0.05. After treatment, cardiac function parameters LvEDD and LVESD levels of observation group were significantly lower than those of control group while EV and AV levels were significantly higher than those of control group (P<0.05; serum myocardial injury indexes ICTP and IMA contents of observation group were significantly lower than those of control group while CysC content was significantly higher than that of control group (P<0.05; serum inflammatory factors CRP, IL-18, IL-27 and MDC contents of observation group were significantly lower than those of control group while IL-10 content was significantly higher than that of control group (P<0.05. Conclusion: Erythropoietin combined with interventional therapy can play a positive role in myocardial protection, improve cardiac pump function, reduce myocardial cell injury and inhibit inflammatory response.

  7. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study.

    Science.gov (United States)

    Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John J V; Califf, Robert M; Krum, Henry

    2013-12-09

    To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. NAVIGATOR trial. Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. ClinicalTrials.gov NCT00097786.

  8. Management and predictors of outcome in unselected patients with cardiogenic shock complicating acute ST-segment elevation myocardial infarction: results from the Bremen STEMI Registry.

    Science.gov (United States)

    Backhaus, Tina; Fach, Andreas; Schmucker, Johannes; Fiehn, Eduard; Garstka, Daniela; Stehmeier, Janina; Hambrecht, Rainer; Wienbergen, Harm

    2017-12-11

    Patients with ST-segment elevation myocardial infarction (STEMI) and consecutive cardiogenic shock (CS) represent a challenge in clinical practice. Only few 'real-world' data on therapeutic management and outcome exist. The present analysis focuses on changes of clinical management of STEMI-patients with CS and analyzes predictors of outcome using the Bremen-STEMI registry. Out of 7865 patients with STEMI, 981 patients (13%) presented with CS. Most CS patients (88%) underwent an early percutaneous intervention (PCI). Intraaortic balloon pumps (IABP) were less implanted since 2013 (p patients with CS was 37%, 1 year mortality was 50%. A significantly reduced 1-year mortality (2006-2009: 55%, 2010-2013: 50%; 2014-2015: 43%, p = 0.027) was observed. In a multivariate analysis significant predictors of an increased 1-year mortality were acute renal failure (OR 3.6; 95% CI 1.9-7.0), atrial fibrillation (OR 2.8; 95% CI 1.3-6.0), three-vessel disease (OR 2.5; 95% CI 1.3-4.7), age ≥ 75 years (OR 2.4, 95% CI 1.3-4.4) and anemia (OR 1.9; 95% CI 1.1-3.3). A successful performed PCI (OR 0.5, 95% CI 0.2-0.9) was associated with a significantly reduced 1-year mortality. management of patients with CS changed with a steep decrease of IABP implantations. Mortality of patients with CS decreased over the last 10 years. Especially, performance of successful PCI was associated with a reduction of mortality, indicating the crucial role of early revascularization to improve prognosis in this high-risk cohort of STEMI-patients.

  9. Television viewing time among statin users and non-users. The Polish Norwegian Study (PONS

    Directory of Open Access Journals (Sweden)

    Georgeta D. Vaidean

    2017-09-01

    In conclusion, we found a higher prevalence of prolonged TV-viewing among statin users than non-users. Future studies are needed to explore innovative behavioral interventions and patient counseling strategies to reduce TV viewing among statin users.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

    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

  12. Selected statins produce rapid spinal motor neuron loss in vitro

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    Murinson Beth B

    2012-06-01

    Full Text Available Abstract Background Hmg-CoA reductase inhibitors (statins are widely used to prevent disease associated with vascular disease and hyperlipidemia. Although side effects are uncommon, clinical observations suggest statin exposure may exacerbate neuromuscular diseases, including peripheral neuropathy and amyotrophic lateral sclerosis. Although some have postulated class-effects, prior studies of hepatocytes and myocytes indicate that the statins may exhibit differential effects. Studies of neuronal cells have been limited. Methods We examined the effects of statins on cultured neurons and Schwann cells. Cultured spinal motor neurons were grown on transwell inserts and assessed for viability using immunochemical staining for SMI-32. Cultured cortical neurons and Schwann cells were assessed using dynamic viability markers. Results 7 days of exposure to fluvastatin depleted spinal motor neurons in a dose-dependent manner with a KD of  Conclusions It is known from pharmacokinetic studies that daily treatment of young adults with fluvastatin can produce serum levels in the single micromolar range. We conclude that specific mechanisms may explain neuromuscular disease worsening with statins and further study is needed.

  13. Impact of prescription size on statin adherence and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Mehler Phillip S

    2007-10-01

    Full Text Available Abstract Background Therapy with 3-Hydroxy-3-methylglutaryl Co-enzyme A reductase inhibitors (statins improve outcomes in a broad spectrum of patients with hyperlipidemia. However, effective therapy requires ongoing medication adherence; restrictive pharmacy policies may represent a barrier to successful adherence, particularly among vulnerable patients. In this study we sought to assess the relationship between the quantity of statin dispensed by the pharmacy with patient adherence and total cholesterol. Methods We analyzed a cohort of 3,386 patients receiving more than one fill of statin medications through an integrated, inner-city health care system between January 1, 2000 and December 31, 2002. Our measure of adherence was days of drug acquisition divided by days in the study for each patient, with adequate adherence defined as ≥ 80%. Log-binomial regression was used to determine the relative risk of various factors, including prescription size, on adherence. We also assessed the relationship between adherence and total cholesterol using multiple linear regression. Results After controlling for age, gender, race, co-payment, comorbidities, and insurance status, patients who obtained a majority of fills as 60-day supply compared with 30-day supply were more likely to be adherent to their statin medications (RR 1.41, 95% CI 1.28–1.55, P Conclusion In a healthcare system serving predominantly indigent patients, the provision of a greater quantity of statin medication at each prescription fill contributes to improved adherence and greater drug effectiveness.

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

    Science.gov (United States)

    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

  15. Gender differences in side effects and attitudes regarding statin use in the Understanding Statin Use in America and Gaps in Patient Education (USAGE) study.

    Science.gov (United States)

    Karalis, Dean G; Wild, Robert A; Maki, Kevin C; Gaskins, Ray; Jacobson, Terry A; Sponseller, Craig A; Cohen, Jerome D

    2016-01-01

    Statin therapy has been shown to reduce cardiovascular morbidity and mortality, and the benefits of statin therapy are similar for men and women. Recent studies have shown that women are less likely to be treated with statin therapy, to be on higher doses of more potent statins, and to achieve their lipid goals as compared with men. To analyze results from the Understanding Statin Use in America and Gaps in Patient Education (USAGE) survey and to assess whether women differ from men with regard to reported side effects associated with statin use, clinician and patient interactions, as well as general attitudes and preferences regarding statin use. The study population was derived from participants in the USAGE survey, a self-administered, Internet-based questionnaire. More women reported switching or stopping a statin because of side effects compared with men. New or worsening muscle symptoms were reported in 31% of women compared with 26% of men (P statins, but less likely to use alternative low-density lipoprotein cholesterol-lowering drugs. Women were more likely to be dissatisfied with their statin, with how their clinician explained their cholesterol treatment, and less adherent to their statin than men. Women are more likely to stop or switch their statin than men, and the main reason for this was new or worsening muscle symptoms. Improved communication between the clinician and the patient about the benefits and risks of statin therapy will improve adherence, lipid goal attainment, and outcomes in women with or at risk for cardiovascular disease. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  16. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  17. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2008-01-01

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

  1. Efficacy of Local and Systemic Statin Delivery on the Osseointegration of Implants: A Systematic Review.

    Science.gov (United States)

    Kellesarian, Sergio Varela; Al Amri, Mohammad D; Al-Kheraif, Abdulaziz A; Ghanem, Alexis; Malmstrom, Hans; Javed, Fawad

    In indexed literature, a systematic review of the efficacy of statins in enhancing osseointegration is lacking. The aim of this systematic review was to assess the efficacy of local and systemic statin delivery on the osseointegration of implants. To address the focused question, "Does local and systemic statin delivery affect osseointegration around implants?", indexed databases were searched from 1965 through November 2015 using various keywords. Letters to the Editor, case reports/case series, historic reviews, and commentaries were excluded. The pattern of this systematic review was customized to primarily summarize the pertinent data. Nineteen studies were included. All studies were experimental and were performed in animal models. In seven studies, statins were delivered systemically via oral, intraperitoneal, intraosseous, subcutaneous, and percutaneous routes. Among the 12 studies, where statins were delivered locally, statin-coated implants were used in seven studies, whereas in the remaining studies, statins were delivered via topical application on the bone cavities. The follow-up duration ranged between 1 and 12 weeks. Results from 18 studies showed that statin administration enhanced new bone formation (NBF) around implants and/or bone-to-implant contact. One study showed that statin-coated implant surfaces impaired osseointegration. Seven studies reported that statin administration enhanced NBF around implants in osteoporotic rats. On experimental grounds, local and systemic statin delivery seems to enhance osseointegration; however, from a clinical perspective, further studies are needed to assess the role of statins in promoting osseointegration around dental implants.

  2. Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive lipids control and diabetes prevention?

    Directory of Open Access Journals (Sweden)

    Tenenbaum Alexander

    2012-11-01

    , induced atherosclerotic plaque regression in thoracic and abdominal aorta and improved endothelial function. In addition, bezafibrate has important fibrinogen-related properties and anti-inflammatory effects. In clinical trials bezafibrate was highly effective for cardiovascular risk reduction in patients with metabolic syndrome and atherogenic dyslipidemia. The principal differences between bezafibrate and other fibrates are related to effects on glucose level and insulin resistance. Bezafibrate decreases blood glucose level, HbA1C, insulin resistance and reduces the incidence of T2DM compared to placebo or other fibrates. Currently statins are the cornerstone of the treatment and prevention of cardiovascular diseases related to atherosclerosis. However, despite the increasing use of statins as monotherapy for low density lipoprotein- cholesterol (LDL-C reduction, a significant residual cardiovascular risk is still presented in patients with atherogenic dyslipidemia and insulin resistance, which is typical for T2DM and metabolic syndrome. Recently, concerns were raised regarding the development of diabetes in statin-treated patients. Combined bezafibrate/statin therapy is more effective in achieving a comprehensive lipid control and residual cardiovascular risk reduction. Based on the beneficial effects of pan-PPAR agonist bezafibrate on glucose metabolism and prevention of new-onset diabetes, one could expect a neutralization of the adverse pro-diabetic effect of statins using the strategy of a combined statin/fibrate therapy.

  3. Balanced pan-PPAR activator bezafibrate in combination with statin: comprehensive lipids control and diabetes prevention?

    Science.gov (United States)

    Tenenbaum, Alexander; Fisman, Enrique Z

    2012-11-14

    atherosclerotic plaque regression in thoracic and abdominal aorta and improved endothelial function. In addition, bezafibrate has important fibrinogen-related properties and anti-inflammatory effects. In clinical trials bezafibrate was highly effective for cardiovascular risk reduction in patients with metabolic syndrome and atherogenic dyslipidemia. The principal differences between bezafibrate and other fibrates are related to effects on glucose level and insulin resistance. Bezafibrate decreases blood glucose level, HbA1C, insulin resistance and reduces the incidence of T2DM compared to placebo or other fibrates. Currently statins are the cornerstone of the treatment and prevention of cardiovascular diseases related to atherosclerosis. However, despite the increasing use of statins as monotherapy for low density lipoprotein- cholesterol (LDL-C) reduction, a significant residual cardiovascular risk is still presented in patients with atherogenic dyslipidemia and insulin resistance, which is typical for T2DM and metabolic syndrome. Recently, concerns were raised regarding the development of diabetes in statin-treated patients. Combined bezafibrate/statin therapy is more effective in achieving a comprehensive lipid control and residual cardiovascular risk reduction. Based on the beneficial effects of pan-PPAR agonist bezafibrate on glucose metabolism and prevention of new-onset diabetes, one could expect a neutralization of the adverse pro-diabetic effect of statins using the strategy of a combined statin/fibrate therapy.

  4. Pleiotropic vasoprotective effects of statins: The chicken or the egg?

    Directory of Open Access Journals (Sweden)

    Dimitrios Kirmizis

    2009-06-01

    Full Text Available Dimitrios Kirmizis, Dimitrios ChatzidimitriouAristotle University, Thessaloniki, GreeceAbstract: Statins (3-hydroxy-3-methyl glutaryl coenzyme A [HMG-CoA] reductase inhibitors are the most commonly used lipid-lowering drugs. Their main lipid-lowering effect is achieved by an increase in the expression of low-density lipoprotein cholesterol receptors associated with inhibition of cholesterol synthesis through inhibition of HMG-CoA reductase – the first and rate-limiting step in cholesterol synthesis. However, beyond cholesterol synthesis inhibition, inhibition of the HMG-CoA reductase affects as well the synthesis of other molecules with significant roles in different, yet often intercalating, metabolic pathways. On this basis, and supported by an increasing series of advocating epidemiological and experimental data, an extended dialogue has been established over the last few years regarding the nonlipid or “pleiotropic” actions of statins.Keywords: statins, immunomodulatory, pleiotropic effects

  5. Statin use and mortality among ovarian cancer patients

    DEFF Research Database (Denmark)

    Verdoodt, Freija; Kjær Hansen, Merete; Kjaer, Susanne K.

    2017-01-01

    Statin use has been suggested to improve prognosis in cancer patients, however, for ovarian cancer, the evidence is sparse. From the Danish Cancer Registry, we identified patients aged 30–84 years with a histologically verified first diagnosis of epithelial ovarian cancer between 2000 and 2013....... Data on filled prescriptions, death, and potential confounding factors were obtained from nationwide registers. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post-diagnostic statin use and all......-cause or ovarian cancer-specific mortality. Among 4,419 patients with epithelial ovarian cancer, post-diagnostic statin use was not statistically significantly associated with all-cause (HR: 0.90, 95% CI: 0.78–1.04) or ovarian cancer-specific mortality (HR: 0.90, 95% CI: 0.76–1.08). There was little evidence...

  6. The MI SYNTAX score for risk stratification in patients undergoing primary percutaneous coronary intervention for treatment of acute myocardial infarction: A substudy of the COMFORTABLE AMI trial

    NARCIS (Netherlands)

    Magro, Michael; Räber, Lorenz; Heg, Dik; Taniwaki, Masanori; Kelbaek, Henning; Ostojic, Miodrag C.; Baumbach, Andreas; Tüller, David; von Birgelen, Clemens; Roffi, Marco; Pedrazzini, Giovanni; Kornowski, Ran; Weber, Klaus; Meier, Bernard; Lüscher, Thomas F.; Serruys, Patrick W.; Jüni, Peter; Windecker, Stephan

    2014-01-01

    Background To investigate the performance of the MI Sxscore in a multicentre randomised trial of patients undergoing primary percutaneous coronary intervention (PPCI). Methods and results The MI Sxscore was prospectively determined among 1132 STEMI patients enrolled into the COMFORTABLE AMI trial,

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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.

  9. Is Prior Statin Therapy Associated with Increased Hemorrhagic ...

    African Journals Online (AJOL)

    Les statines ont été proposées pour augmenter le risque d'AVC hémorragique. Nous émettons l'hypothèse que, avant un traitement par statine chez les patients admis avec AVC hémorragique ou ischémique dans une population Grampian serait associée à un risque accru d'hémorragie cérébrale intra (ICH) plutôt que de ...

  10. Glycosylated hemoglobin is associated with decreased endothelial function, high inflammatory response, and adverse clinical outcome in non-diabetic STEMI patients.

    Science.gov (United States)

    Moura, Filipe A; Figueiredo, Valeria N; Teles, Bruna S B S; Barbosa, Meyrianne A; Pereira, Lara R; Costa, Ana P R; Carvalho, Luiz Sergio F; Cintra, Riobaldo M R; Almeida, Osório L R; Quinaglia E Silva, Jose C; Nadruz Junior, Wilson; Sposito, Andrei C

    2015-11-01

    Chronic dysglycemia was recently identified as a predictor for adverse outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. Data for non-diabetic patients who underwent thrombolysis is scarce. In this context, we aimed to study the effect of HbA1c on cardiovascular outcome after STEMI. A prospective cohort of 326 non-diabetic STEMI individuals was used for the analyses. We measured plasma glucose, hemoglobin A1c [HbA1c], lipid profile, C-reactive protein (CRP), and nitrate/nitrite (NOx) upon admission and five days after STEMI (D5). Flow-mediated dilation (FMD) was performed 30 days after STEMI. During clinical follow-up, we assessed patients for incident diabetes (progression to HbA1c ≥ 6.5%) and major adverse cardiac events (MACE), defined as a composite of fatal and non-fatal MI, sudden cardiac death, and angina requiring hospitalization. Using ROC-curve analysis, a 5.8% HbA1c best predicted MACE with a sensitivity of 75% and specificity of 53% (AUC 0.673, p = 0.001). Patients were categorized as high HbA1c if ≥ 5.8% and low HbA1c if <5.8%. Compared with patients with low HbA1c, those with high HbA1c presented with 20% higher CRP-D5 (p = 0.009) and 19% higher ΔCRP (p = 0.01), a 32% decrease in ΔNOx (p < 0.001), and 33% lower FMD (p < 0.001). After a median follow-up of 1.9 (1.1-2.8) years, patients with high HbA1c had more incident diabetes (HR 2.3 95% CI 1.01-5.2; p = 0.048) and MACE (HR 3.32 95% CI 1.09-10.03; p = 0.03). Non-diabetic STEMI patients with high HbA1c present with decreased endothelial function and increased inflammatory response and long-term risk of MACE. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

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

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

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

    Directory of Open Access Journals (Sweden)

    D. A. Sychev

    2015-09-01

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

  13. Role of cathepsin D activation in major adverse cardiovascular events and new-onset heart failure after STEMI.

    Science.gov (United States)

    Yamac, Aylin Hatice; Sevgili, Emrah; Kucukbuzcu, Sitki; Nasifov, Muharrem; Ismailoglu, Ziya; Kilic, Elif; Ercan, Cilem; Jafarov, Parviz; Uyarel, Hüseyin; Bacaksiz, Ahmet

    2015-09-01

    Increased serum levels of the activated aspartic lysosomal endopeptidase cathepsin D (CatD) have been found in patients with acute myocardial infarction (AMI). However, to date there have been no analyses of clinical follow-up data measuring the enzyme course and its role in the development of post-MI heart failure. This study aimed to evaluate the role of serum CatD activity in the development of heart failure in patients with ST-segment elevation acute myocardial infarction (STEMI). Eighty-eight consecutive patients (79.5 % men, mean age 57.4 ± 10.2 years) with STEMI were included in this study. Serum CatD activity was measured directly after primary percutaneous coronary intervention (PCI), before discharge, and at the 6-month follow-up. Patients were monitored for major adverse cardiovascular events (MACE), defined as hospitalization due to cardiovascular causes, recurrent nonfatal myocardial infarction, unplanned PCI, new-onset heart failure, and cardiovascular mortality. Serum CatD activity was significantly higher in patients with AMI after PCI and during follow-up (FU) than that in age-matched controls (16.2 ± 7.5 and 29.8 ± 8.9 vs. 8.5 ± 4.2 RFU; p CatD activity in these patients was inversely related to new-onset cardiac dysfunction compared with patients with preserved and improved LVEF after treatment (23.1 ± 3.2 vs. 28.8 ± 7.0 and 29.7 ± 5.0 RFU respectively, p CatD than those without any MACE (23.8 ± 4.6 vs 29.6 ± 6.9 RFU; p CatD activity as a marker of healthy endogenous phagocytosis and remodeling was impaired in patients with new-onset cardiac dysfunction, and lower levels of serum CatD were associated with MACE at the 6-month post-MI follow-up.

  14. Rosuvastatin for primary prevention among individuals with elevated high-sensitivity c-reactive protein and 5% to 10% and 10% to 20% 10-year risk. Implications of the Justification for Use of Statins in Prevention

    DEFF Research Database (Denmark)

    Ridker, Paul M; Macfadyen, Jean G; Nordestgaard, Børge G

    2010-01-01

    Recent primary prevention guidelines issued in Canada endorse the use of statin therapy among individuals at "intermediate risk" who have elevated levels of high-sensitivity C-reactive protein (hsCRP). However, trial data directly addressing whether this recommendation defines a patient populatio...

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

    Science.gov (United States)

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

    2016-12-15

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

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

    Science.gov (United States)

    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.

  17. Chronic Statin Use and Long-Term Rates of Sepsis: A Population-Based Cohort Study.

    Science.gov (United States)

    Wang, Henry E; Griffin, Russell; Shapiro, Nathan I; Howard, George; Safford, Monika M

    2016-07-01

    "Statins" have immunomodulatory and anti-inflammatory effects and may attenuate the risk of infections. We sought to determine the association between chronic statin use and long-term rates of sepsis events. We used data from 30 183 adult (≥45 years old) community-dwelling participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The primary exposure was statin use. The primary outcome was hospitalization or emergency department treatment for sepsis. Using Cox proportional hazards models, we determined associations between statin use and first sepsis events, adjusting for patients demographics, health behaviors, chronic medical conditions, degree of medication adherence, baseline high-sensitivity C-reactive protein (hsCRP), and propensity for statin use. Approximately one-third of participants reported statin use (n = 9475, 31.4%). During the 10-year follow-up period from 2003 to 2012, there were 1500 incident sepsis events. Statin use was not associated with rates of sepsis after multivariable adjustment for demographics, health behaviors, chronic medical conditions, medication adherence, abnormal hsCRP, and propensity for statin use, hazard ratio 0.93 (95% confidence interval: 0.81-1.06). Statin use was not similarly associated with rates of sepsis when stratified by propensity for statin use or medication adherence. In the REGARDS cohort, statin use at baseline was not associated with rates of future sepsis events. © The Author(s) 2014.

  18. Statin usage, vascular diagnosis and vascular risk factors in Parkinson's disease.

    Science.gov (United States)

    Cheng, Kelvin Kw; Swallow, Diane Ma; Grosset, Katherine A; Grosset, Donald G

    2017-08-01

    Background and aims Vascular disease is a common comorbidity in Parkinson's disease patients. Statins are potentially neuroprotective for Parkinson's disease through non-vascular mechanisms. We investigated prevailing statin use in a Parkinson's disease cohort. Methods and results Data on diagnostic indication for statins, anti-Parkinson therapy, vascular risk factors, and statin prescription, were obtained from electronic medical record review for consecutive Parkinson's disease patients. The ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network system was used to calculate future cardiovascular risk and identify those warranting statin use. Of 441 patients included, 59.9% were male, with a mean age of 68.9 years (standard deviation 10.3). One hundred and seventy-four (39.5%) patients had at least one diagnostic indication for statin use, of whom 136 (78.2%) were prescribed a statin. In the 267 (60.5%) cases without a diagnostic indication, 54 (20.2%) were excluded owing to age limitations defined in ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network. Of the remaining 213, 62 (29.1%) had an ASsessing cardiac risk using Scottish Intercollegiate Guidelines Network score in the recommended range for statin therapy, of whom 15 (24.1%) were prescribed statins. Conclusion There is suboptimal implementation of statin therapy in Parkinson's disease patients. Given the possible neuroprotective effects of statins in Parkinson's disease in addition to reducing cardiovascular risk, reasons for suboptimal implementation warrant further investigation.

  19. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes

    NARCIS (Netherlands)

    Cannon, Christopher P.; Blazing, Michael A.; Giugliano, Robert P.; McCagg, Amy; White, Jennifer A.; Theroux, Pierre; Darius, Harald; Lewis, Basil S.; Oude Ophuis, Ton; Jukema, J. Wouter; de Ferrari, Gaetano M.; Ruzyllo, Witold; de Lucca, Paul; Im, KyungAh; Bohula, Erin A.; Reist, Craig; Wiviott, Stephen D.; Tershakovec, Andrew M.; Musliner, Thomas A.; Braunwald, Eugene; Califf, Robert M.; Musliner, Thomas; Tershakovec, Andrew; Gurfinkel, Enrique; Aylward, Philip; Tonkin, Andrew; Maurer, Gerald; van de Werf, Frans; Nicolau, Jose C.; Genest, Jacques; Armstrong, Paul; Corbalan, Ramon; Isaza, Daniel; Spinar, Jindrich; Grande, Peer; Voitk, Juri; Kesaniemi, Antero; Bassand, Jean-Pierre; Farnier, Michel; Keltai, Matyas; Mathur, Atul; Mittal, Sanjay; Reddy, Krishna; Lewis, Basil; White, Harvey; Pedersen, Terje; Britto, Frank; Carrageta, Manuel; Duris, Tibor; Dalby, Anthony; Seung, Ki-Bae; Lopez-Sendon, Jose; Dellborg, Mikael; Mach, Francois; Guneri, Sema; Parkhomenko, Alexander; Brady, Adrian; Cannon, Christopher; Blazing, Michael; Ballantyne, Christie; de Lemos, James; Kleiman, Neal; McGuire, Darren K.; Gurfinkel, E.; Centeno, E.; Casalins, M.; Cartasegna, L.; Beltrano, M. C.; Guerrero, R. Ahuad; Fanuele, M.; Berra, F. Colombo; Egido, J.; Colombo, H.; Dellatorre, M.; Terns, P. Perez; Blumberg, E. Salmon; Reges, P.; Azize, G.; Ramos, H.; Fernandez, R.; Carlessi, C. A.; Milesi, R.; Schmuck, R.; Duronto, E.; Procopio, G.; Carlevaro, O.; Maffeo, H.; Beloscar, J.; Viso, M.; Hominal, M.; Castoldi, M.; Bluguermann, J.; Mauro, D.; Macin, S.; Cocco, N.; Ruiz, N.; Ricart, J. P.; Lozada, A.; Nani, S.; Turri, D.; Fernandez, H.; Caruso, O.; Zarandon, R. Saa; Bono, J.; Arias, V.; Allall, O.; Marino, J.; Cusimano, S.; Schygiel, P.; Buzetti, C.; Penaloza, N.; Berli, M.; Aylward, P.; Worthley, S.; Roach, A.; Chew, D.; Wright, T.; Leitch, J.; Hicks, E.; Rankin, J.; Venn-Edmonds, C.; Lehman, R.; Morrison, H.; Shaw, J.; Mak, V.; Hii, C.; Smith, K.; Cross, D.; Lilwall, L.; Nelson, G.; Loxton, A.; Horowitz, J.; Rose, J.; Maurer, G.; Steinwender, C.; Leisch, F.; Kammler, J.; Brussee, H.; Zweiker, R.; Niederl, E.; Weihs, W.; Giorgio, G.; Lang, I.; Drexel, H.; Zanolin, D.; Hoppe, U.; Atzenhofer-Baumgartner, K.; Pichler, M.; Hainzer, D.; Eber, B.; Pichler, F.; Foeger, B.; Wechselberger, T.; Mayr, H.; Hofer, J.; Stockenhuber, F.; Warlits, B.; Huber, K.; Egger, F.; Weidinger, F.; Ziegler, B.; Jirak, P.; Metzler, B.; Pachinger, O.; Wanitschek, M.; Auer, J.; Grabscheit, G.; Podczeck-Schweighofer, A.; Priesnitz, T.; Frank, H.; Van de Werf, F.; El Allaf, D.; Marechal, P.; Roosen, J.; Joly, E.; Lefebvre, P.; Arend, C.; Sinnaeve, P.; de Velder, L.; Hellemans, S.; Vanhauwaert, B.; van Dorpe, A.; Heyse, A.; Vantomme, C.; Striekwold, H.; van den Broeck, D.; Lancellotti, P.; Schoors, D.; Lemoine, I.; Taeymans, Y.; de Wolf, L.; Brike, C.; Vercauteren, S.; Tahon, S.; Vervoort, G.; Mestdagh, I.; Pirenne, B.; Cardinal, F.; Lips, S.; Dujardin, K.; Debrouwer, K.; Dhooghe, G.; Holvoet, G.; van de Borne, P.; Renard, M.; de Clippel, M.; Lesseliers, H.; van Miert, N.; Nicolau, J. C.; Saraiva, J.; Vicente, C.; Rossi, P. Ferreira; Dos Santos, L. B.; Duda, N.; Tognon, A. P.; Serrano, C. Vicente; Gomes, F. L. T.; Manenti, E. R. Fernandes; Silveira, D. S.; Maia, L.; Mouco, O. M. C. C.; Paiva, M. Moura de Oliveira; Antonangelo, A. Francisco de Paula; de Souza, J. Ascenção; Lino, E. A. G.; Leães, P.; Blacher, M. G.; Kormann, A. Morales; Ultramari, F. T.; Dutra, O.; Mendelski, A. M.; Morgado, S.; Ardito, W.; Greque, G.; Ardito, R. V.; Pimentel Filho, P.; Zucchetti, C.; Alves, A.; Seabra, A. M. L.; Mattos, M.; Miranda, L. F. C.; Silva, D.; Uehara, R. M.; Marin Neto, J.; Schmidt, A.; Braga, J. Ferreira; Rodrigues, A.; Abrantes, J.; Pinheiro, L. O.; Bodanese, L.; Magedanz, É H.; Piegas, L.; Dos Santos, E. S.; Wainstein, M. Vugmann; Ribeiro, J.; Stein, R.; Marino, R.; Machado, V. M.; Moraes Junior, J.; Guimarães, S.; da Costa, F. Alves; Ferraz, R. F.; Albuquerque, D.; Rocha, R. M.; de Carvalho Moreira, R.; Dohmann, H.; Costantini, C. Ortiz; Tarastchuk, J. C. E.; Coelho, O.; Cirillo, W.; Sousa, A.; Almeira, A. S.; Stefanini, E.; Silva, F.; Teixeira, M.; da Cunha, C. Pereira; Précoma, D. Bertolim; Facchi, T. L. S.; Theroux, P.; Rupka, D.; Thiessen, S.; Warnica, J.; Smith, B.; Della Siega, A.; Klinke, P.; Nelson, S.; Dion, D.; Gilbert, N.; Hui, W.; Kvill, L.; Sussex, B.; Luther, A. Marie; Dupuis, R.; Ouimet, F.; Pandey, A.; Clarus, S.; Senaratne, M.; Ferdinandis, H.; Mukherjee, A.; Bozek, B.; Vizel, S.; Markov, G.; Zimmermann, R.; Stephens, W.; Tremblay, B.; Wong, G.; Uchida, N.; Brossoit, R.; Peck, C.; van Kieu, C.; Forgione, M.; Bata, I.; Cossett, J.; Kostuk, W.; Arnold, M.; Bone, C.; Grondin, F.; Bilodeau, N.; Gosselin, G.; David, M.; Giannoccaro, J.; Beresford, P.; Polasek, P.; Roberts, P.; Doucet, M.; Beaudry, M.; Cheung, S.; Cleveland, T.; Bhargava, R.; McCallum, A.; Ma, P.; Morrissette, J.; Cleveland, D.; Chadwyn, D. L.; Nigro, F.; Weeks, A.; Cryderman, C.; Leader, R.; Houde, G.; Rousseau, S.; Pearce, M.; Radyk, M.; Lonn, E.; Magi, A.; Lefkowitz, C.; Sandrin, F.; Coffin, N.; Lubelsky, B.; Coldwell, J.; Habot, J.; McPherson, C.; de Larochelliere, R.; Roy, M.; Haichin, R.; Barber, C.; Bhesania, T.; Kitagawa, H.; To, T.; Donnelly, B.; Tymchak, W.; Harris, L.; Kouz, S.; Huynh, T.; St Jacques, B.; Lamy, A.; Rizzo, A.; Stein, J.; Childs, C.; Wong, B.; Poirier, R.; Gupta, M. K.; Dela Cruz, C.; Constance, C.; Gauthier, M.; Ervin, F.; Ouellette, M.; Kokis, A.; Lemay, C.; Kwok, K.; Leung, C.; Lee, D. S.; Nesmith, J.; Renton, J.; Syan, G.; Turek, M.; Hogan, D.; Griffin, P.; Lipson, A.; Winestock, J.; Abramson, B. L.; Fogel, A.; Gagne, C.; Bergeron, J.; Clarke, A.; Slipp, S.; Darcel, I.; Carling-Chambers, L.; Kannampuzha, P.; Pallie, S.; Krekorian, S.; Vertes, G.; Roth, S.; Lai, K.; Heath, J.; Corbalan, R.; Perez, L.; Arriagada, G.; Castro, P.; Villa, F.; Rodríguez, M.; Ramos, G.; Baraona, F.; Núñez, A.; García, M.; Jofre, C. Pincetti; Silva, P.; Lamich, R.; Yovaniniz, P.; Escobar, E.; Dussaubat, A. Maria; Segura, E.; Ramirez, M.; Lapostol, C.; Palma, A.; Encina, L.; Zapata, M.; Baeza, N.; Varela, P. Sepulveda; Pérez, L.; Isaza, D.; Jaramillo, C.; Ruiz, S.; Sanchez, G.; Perdomo, I.; Manzur, F.; Cohen, L. E.; Velasquez, J.; Arana, C.; Alvarez, Y.; Triana, M. Urina; Balaguera, J.; de Salazar, D. Molina; Rendon, N.; Botero, R.; Ruiz, A.; Saaibi, J.; Medina, J. Castillo; Jaramillo, M.; Calderón, M. J.; Delgado, J.; Bohorquez, R.; Medina, M. F.; Herrera, M.; Rosales, D.; Mendoza, F.; Martinez, S.; Ternera, A.; Castro, R.; Baiz, A. Quintero; Martinez, M.; Orozco, A.; Suarez, M.; Fonseca, Y.; Beltran, R.; Cepeda, M.; Jaramillo, N.; Valenzuela, C.; Gutierrez, M.; Sanchez, A.; Spinar, J.; Vitovec, J.; Hlinomaz, O.; Poloczek, M.; Mayer, O.; Veselka, J.; Vejvoda, J.; Soucek, M.; Spac, J.; Novobilsky, K.; Srp, V.; Francek, L.; Branny, M.; Sknouril, L.; Motovska, Z.; Rohac, F.; Stankova, A.; Fiala, T.; Holub, M.; Zeman, K.; Pohludkova, L.; Pospisilova, E.; TUMA, P.; Cihalik, C.; Oral, I.; Podpera, I.; Stepanovova, R.; Uricar, M.; Solar, M.; Pelouch, R.; Porzer, M.; Grussmannova, K.; Stipal, R.; Reichert, P.; Hradec, J.; Kral, J.; Sejkova, B.; Janek, B.; Pitha, J.; Linhart, A.; Polacek, P.; Grande, P.; Koeber, L.; Clemmensen, P.; Hebin, C. H.; Schmidt, E.; Pedersen, M. S.; Roseva-Nielsen, N.; Kristensen, K. Skoedebjerg; Bang-Hansen, T.; Jensen, J.; Laage-Petersen, J.; Nielsen, H.; Stokholm, E.; Thayssen, P.; Cappelen, H.; Jensen, T.; Winther-Friis, B.; Klausen, I.; Hedegaard, B.; May, O.; Andersen, M.; Bottzauw, J.; Lush, A.; Markenvard, J.; Vestager, K. M.; Bronnum-Schou, J.; Hempel, H.; Petersen, J.; Nielsen, A. J.; Thomsen, K.; Nielsen, T.; Nygaard, A.; Sykulski, R.; Jensen, B. S.; Ralfkiaer, N.; Gottschalck, H.; Rasmussen, S.; Pedersen, L. R.; Dodt, K.; Skovsbøl, M.; Andersen, O.; Tuxen, C.; Meier, A. W.; Kristensen, T.; Rasmussen, O.; Lopez, J.; Salazar, D.; Sanchez, L.; Rosero, F.; Penaherrera, E.; Duarte, Y. C.; Marmol, R.; Andrade, G.; Guzman, E.; Morillo, A.; Voitk, J.; Aug, L.; Loogna, I.; Laanmets, P.; Kesaniemi, A.; Mustonen, J.; Mäntylä, P.; Kesäniemi, A.; Ukkola, O.; Kervinen, H.; Juhela, S.; Juvonen, J.; Toppinen, A.; Jarvenpaa, J.; Syvanne, M.; Svahn, T.; Voutilainen, S.; Huotari, A.; Nikkila, M.; Raiskinmäki, S.; Kotila, M.; Rajala, A.; Laukkanen, J.; Hiltunen, P.; Melin, J.; Nyman, K.; Luukkonen, J.; Kosonen, P.; Huttunen, M.; Seppänen, V.; Airaksinen, J.; Juonala, M.; Lehto, S.; Savolainen, K.; Halkosaari, M.; Sia, J.; Palomaki, A.; Luoma, J.; Utriainen, S.; Valpas, S.; Tiensuu, T.; Lilleberg, J.; Kainulainen, R.; Bassand, J.-P.; Schiele, F.; Bassand, J.; Meneveau, N.; Galinier, M.; Jean, M.; Martelet, M.; Mouallem, J.; Elbaz, M.; Puel, J.; Carrié, D.; Coisne, D.; Varroud-Vial, N.; Jaboureck, O.; Dujardin, J. J.; Leroy, F.; Mansourati, J.; Funck, F.; Jourdain, P.; Guillard, N.; Coviaux, F.; Gay, A.; Dourmap-Collas, C.; Froger-Bompas, C.; Paillard, F.; Tricot, O.; Maquin-Mavier, I.; Dubois-Rande, J. L.; Pongas, D.; Paris, A. P. H.; DELAHAYE, F.; Ovize, M.; Benyahya, L.; Bonnet, J.; Belle, L.; Mangin, L.; Lafitte, B.; Zemour, G.; Doux, N.; Agraou, B.; El Mansour, N.; Traisnel, G.; El Jarroudi, M.; Ohlmann, P.; Diadema, B.; Escande, M.; Legros, G.; Demarcq, J. M.; Haftel, Y.; Alsagheer, S.; Dambrine, P.; Cottin, Y.; Ghostine, S.; Caussin, C.; Gacem, A.; Bouvier, J. M.; Poulard, J.; Davy, J.; Furber, A.; Prunier, F.; Darius, H.; Muenzel, T.; Genth-Zotz, S.; Appel, K.; Kretzschmar, D.; Ferrari, M.; Terres, W.; Uher, T.; Schulze, H.; Ochs, H.; Morbach, S.; Duengen, H.; Gross, M.; Oezcelik, C.; Tahirovic, E.; Heuer, H.; Laschewski, B.; Kadel, C.; Rahn, G.; Steiner, S.; Kreuzer, J.; Tsoy, I.; Zeiher, A.; Muegge, A.; Hanefeld, C.; Boehm, S.; Boudriot, E.; Hodenberg, E.; Lippe, B.; Hausdorf, C.; Sydow, K.; Baldus, S.; Schlesner, C.; Tiroch, K.; Haltern, G.; Guelker, H.; Wilhelm, J.; Dietz, S.; Ebelt, H.; Buerke, M.; Rupprecht, H.; Rittgen, J.; Schaeufele, T.; Meinhardt, G.; Schieber, M.; Honold, M.; Sieprath, S.; Nienaber, C.; Hacker, J.; Butter, C.; Lapp, H.; Hirn, S.; Pauschinger, M.; Zahn, R.; Scheffler, U.; Schaefer, A.; Schieffer, B.; Tebbe, U.; Kriete, M.; Mudra, H.; Raeder, T.; Braun, P.; Zeymer, U.; Kouraki, K.; Reppel, M.; Schunkert, H.; Weil, J.; Olbrich, H.; Schwaiger, P.; Mueller, O.; Blessing, E.; Buss, I.; Bohlscheid, V.; Kaddatz, J.; Skowasch, D.; Nickenig, G.; Twelker, K.; Osterhues, H.; Varghese, T.; Burghard, S.; Kaeaeb, S.; Klauss, V.; Sohn, H. Y.; Hauptmann, K. E.; Schulze, M.; Gall, K.; Felix, S.; Doerr, M.; Mante, J.; Gulba, D.; Freick, M.; Werner, G.; Kleinertz, K.; Hobbach, H. P.; Halbach, M.; Mueller-Ehmsen, J.; Mueller, M. E.; Mitrovic, V.; Peil, A.; Laufs, U.; vom Dahl, J.; Baumanns, S.; Scholtz, W.; Wiemer, M.; Haude, M.; van de Loo, A.; Pistorius, K.; Schaefer, J.; Schwinger, R.; Goeing, O.; Jung, W.; Birkemeyer, R.; Lee, W.; Kong, S.; Yu, C.; Chui, K.; Keltai, M.; Merkely, B.; Szelényi, Z.; Polgár, P.; Svab, S.; Herczeg, B.; Bajcsi, É; Vértes, A.; Davidovits, S.; Nagy, A.; Király, C.; Lupkovics, G.; Kenéz, A.; Poór, F.; Takács, J.; Kirschner, R.; Simonyi, G.; Koncz, J.; Édes, I.; Gergely, S.; Katona, A.; Nagy, E.; Kovács, Z.; Gyetvai, I.; Salamon, C.; Kolman, É; Sitkei, É; Csapó, K.; Molnar, K.; Mező, I.; Sereg, M.; Mathur, A.; Mittal, S.; Reddy, K.; Reddy, P.; Manjunath, C.; Narayanappa, S.; Kumar, S.; Sinha, N.; Kapoor, A.; Christopher, J.; Reddy, G.; Rani, M.; Oomman, A.; Ramamurthee, K.; Kumar, N.; Pasha, S. S.; Rao, C.; Murty, G. S. R.; Chopra, A.; Kapila, D.; Bali, H.; Chattree, K.; Hasan, O.; Suryaprakash, G.; Rao, D. Nageswara; Babu, R.; Bhargavi, M.; Naik, S.; Khan, S.; Chopra, V.; Sapra, R.; Kaul, U.; Ghose, T.; Menon, R.; Battikadi, S.; Mullasari, A.; Subban, V. K.; Dani, S.; Iby, M.; Chandra, P.; Sethi, S.; Bhargava, M.; Arora, P.; Tyagi, G.; Padmanabhan, T.; Malhotra, S.; Talwar, K.; Shafiq, N.; Kasliwal, R.; Bansal, M.; Lewis, B. S.; Eldar, M.; Berger, M.; Shechter, M.; Atar, S.; Roguin, N.; Kilimnik, M.; Hayek, T.; Hamoud, S.; Katz, A.; Plaev, T.; Shotan, A.; Vazan, A.; Weiss, A.; Leibowitz, D.; Zimlichman, R.; Ben-Aharon, J.; Hammerman, H.; Dragu, R.; Rozenman, Y.; Witzling, V.; Tzivoni, D.; Moriel, M.; Halkin, A.; Sheps, D.; Bogomolny, N.; Mosseri, M.; Khudyak, Y.; Halabi, S.; Uziel-Iunger, K.; Yuval, R.; Shimoni, S.; Caspi, A.; Botwin, S.; Gavish, D.; Sandler, A.; Pollak, A.; Kreisberg, B.; Hussein, O.; Jabal, K. Abu; Henkin, Y.; Grosbard, A.; Rosenschein, U.; Rivlin, E.; Zeltser, D.; Platner, N.; Porter, A.; Harel, N.; Lishner, M.; Elis, A.; Karny, M.; Fuchs, S.; Stein, G. Y.; Grossman, E.; Gealel, Z.; Schlaeffer, F.; Liberty, I.; Golik, A.; Tzuman, O.; de Ferrari, G. M.; Pavesi, C.; Poggio, L.; Damiano, S.; Pazzano, A. S.; Mennuni, M.; Paloscia, L.; Mascellanti, M.; Piovaccari, G.; Grosseto, D.; Mascia, F.; Vetrano, A.; Zingarelli, A.; Mazzantini, S.; Visconti, L. Oltrona; Terzi, G.; Senni, M.; Gavazzi, A.; Scuri, P.; Carmelo, M.; de Caterina, R.; Conti, M.; Novo, S.; Graceffa, A.; Arvigo, L.; Lunetta, M.; Filardi, P. Perrone; Chiariello, M.; Scala, O.; Pirozzi, E.; Musella, F.; Moretti, L.; Testa, M.; Vicentini, A.; de Feo, S.; Biasucci, L.; Cardillo, M. T.; Puccioni, E.; Galli, M.; Menegato, A.; Margheri, M.; Maresta, A.; Gatti, C.; Guarini, P.; Damiano, M.; Golino, P.; Porcu, M.; Fele, N.; Gensini, G.; Lombardi, A.; Ciuti, G.; Bernardi, D.; Mariani, P.; Paolini, E.; Marenzi, G.; Moltrasio, M.; Terrosu, P.; Chessa, P.; Guglielmino, G.; Miccoli, F.; Oldoino, E.; Ragni, M.; Poli, M.; Basso, V.; Rapezzi, C.; Branzi, A.; Gallelli, I.; Perna, G. P.; Guazzarotti, F.; Marra, S.; Usmiani, T.; Olivari, Z.; Calzolari, D.; Santoro, G.; Minneci, C.; Achilli, A.; Nassiacos, D.; Sommariva, L.; Romeo, F.; Fedele, F.; Foschi, M. L.; Bruno, N.; Centurion, C.; Patrizi, G.; de Maria, E.; Gonnelli, S.; Vichi, V.; Cassadonte, F.; Rotella, G.; Capucci, A.; Villani, G.; Gaspardone, A.; Ferrante, R.; Scollo, V.; Pancaldi, L.; Saccà, S.; Gabrielli, D.; Ciliberti, D.; Savini, E.; Binaghi, G.; Di Biase, M.; Ieva, R.; Fattore, L.; Cicia, G.; Cavallini, C.; Tamburino, C.; Sacco, A.; Mafrici, A.; Di Pasquale, G.; Pavesi, P. C.; Scioli, R.; Lioy, E.; Occhiuzzi, E.; Matino, M. G.; Russo, V.; Moscogiuri, M. G.; Cuccia, C.; Forgione, C.; Volpe, M.; Palano, F.; Branca, G.; ROSSI, R.; Modena, M.; Olaru, I. A.; Zanini, R.; Cianflone, D.; Cristell, N.; Pantaleoni, M.; Guiducci, U.; Menozzi, C.; Gaddi, O.; Fasulo, A.; Indolfi, C.; Emanuele, V.; Guerra, F.; Iliceto, S.; Marotta, C.; Morocutti, G.; Presbitero, P.; Rossi, M.; Bonatti, S.; Grieco, A.; Chiodi, L.; Betti, I.; Zuppiroli, A.; Fanelli, R.; Stanco, G.; Azzolini, P.; Ruggieri, C.; Bocconcelli, P.; Airoldi, F.; Tavano, D.; Brunelli, C.; Caso, P.; Scalzone, A.; Ghigliotti, G.; Facciorusso, A.; Sim, K.; Kiam, O. Tiong; Chee, K. H.; Bin Ismail, O.; Zambahari, R.; Oude Ophuis, T.; Jukema, J. Wouton; van Nes, E.; Werter, C. J. P. J.; Oude Ophuis, A. J. M.; Troquay, R. P. Th; Hamer, B. J. B.; Lenderink, T.; Feld, R. J. C. T.; van Hessen, M. W. J.; Viergever, E. P.; van der Sluis, A.; Lok, D. J. A.; Badings, E. A.; Nierop, P. R.; Danse, I. Y.; Hermans, W. R. M.; Holwerda, N. J.; Thijssen, H. J. M.; Theunissen, L. J. H. J.; van der Zwaan, C.; van den Berg, B. J.; Hendriks, I. H. G. M.; Ronner, E.; Withagen, A. J. A. M.; Dijkshoorn-Giesen, A. H. J. M.; Ezechiels, J. P.; Kuijper, A. F. M.; den Hartog, F. R.; van Kalmthout, P. M.; Buijs, E. M.; van der Zeijst, M.; Zwart, P. A. G.; Zuidgeest, J. A. M.; van Eck, M.; Daniels, M. C. G.; van der Ven-Elzebroek, N.; van 't Hof, A.; van Boven, A. J.; van der Weerdt, A.; Dunselman, P. H. J. M.; Alings, M. A.; van Es, R. F.; The, S. H. K.; Gurlek, C.; Liem, A. H.; van Lennep, H. W. O. Roeters; van Vlies, B.; Kalkman, C.; Swart, H. P.; van der Bij, P.; Taverne, R.; Ciampricotti, R.; van Dam, C.; Spierenburg, H.; van Ruijven, I.; van Kempen, L. H. J.; Willems, F. F.; Dirkali, A.; Stoel, I.; Plomp, J.; Veldmeijer, S.; Tjeerdsma, G.; Nijmeijer, R.; van Hal, J. M. C.; Bartels, G. L.; Posma, J. L.; Linssen, G. C. M.; Fauser, C. G. K. M.; Waalewijn, R. A.; Groenemeijer, B. E.; Pos, L.; Fast, J. H.; Droste, H. T.; Westenburg, J.; Veenstra, W.; Koolen, J.; van Loo, L. W. H.; Smits, W.; Milhous, J. G. J.; van Rossum, P.; Stuij, S.; White, H.; Scott, R.; Richards, A. M.; Morrison, Z.; Devlin, G.; Fisher, R.; Stewart, R.; Benetar, J.; Voss, J.; Wong, S.; Scott, D.; Luke, R.; Tang, E. W.; Davidson, L.; Hamer, A.; Wilson, S.; Price, R.; Hart, H.; Turner, A.; Pedersen, T.; Jortveit, J.; Calic, S.; Gundersen, T.; Brunvand, H.; Fosse, L.; Nygaard, O.; Gjellefall, B.; Gravdal, S. A.; Ringstad, R.; Atar, D.; Clausen, H.; Hysing, J.; Arvesen, K.; Topper, M.; Flagstad, E.; Graven, T.; Haug, H. H.; Dalin, L.; Al-Ani, R.; Otterstad, J. E.; Ausen, K.; Aaser, E.; Olufsen, M.; Halvorsen, S.; Gullestad, L.; Stueflotten, W.; Waage, K.; Stødle, R. M.; Hall, C.; Aase, O.; Nordeng, J.; Soyland, E.; Fageraas, E. R.; Lied, A.; Aske, R.; Raouf, N.; Johansson, J.; Herrscher, T.; Skogrand, E.; Bjornstad, H.; Aagnes, I.; Arntsen, B. I.; Vegsundvaag, J.; Skjold, M. E.; Velle, H.; Aambakk, M. B.; Skjetne, O.; Byfuglien, A.; Britto, F.; Rodriguez, J.; Galvez, D.; Medina, F.; Hernandez, H. A. Anchante; Chavez, V. Rodriguez; Morales, R.; Huapalla, E. Chavez; Velasquez, D.; Torres, F.; Aguirre, O.; Yanez, L. Toce; Andrade, M.; Campos, C.; Arce, R.; Mogrovejo, W.; Osores, F.; Bustamante, G.; Rodriguez, M.; Berrospi, P.; Garcia, C.; Talledo, M. Zubiate; Navarro, P. Rios; Horna, M.; Herrera, V.; Ruzyllo, W.; Kadziela, J.; Rybicka-Musialik, A.; Trusz-Gluza, M.; Berger-Kucza, A.; Musial, W.; Tycinska, A.; Gil, R.; Gziut, A.; Gorny, J.; Tyllo, M.; Reszka, Z.; Mickiewicz-Pawlowska, M.; Wrzosek, B.; Kosior, J.; Staneta, P.; Korzeniak, R.; Kalarus, Z.; Markowicz, E.; Miekus, P.; Konarzewski, M.; Kleinrok, A.; Puzniak, M.; Grajek, S.; Janus, M.; Krzyzanowski, M.; Hoffmann, A.; Muzalewski, P.; Polonski, L.; Kazik, A.; Nowalany-Kozielska, E.; Wojciechowska, C.; Ponikowski, P.; Nawrocka, S.; Filipiak, K.; Serafin, A.; Dubiel, J.; Mielecki, W.; Ogorek, M.; Kopcik, D.; Jaworska, K.; Skonieczny, G.; Kawecka-Jaszcz, K.; Bryniarski, L.; Tracz, W.; Lesniak-Sobelga, A.; Jankielewicz, J.; Zaluska, R.; Trojnar, R.; Kawalek, P.; Gaciong, Z.; Pulkowski, G.; Anaszewicz, M.; Samul, W.; Adamus, J.; Cholewa, M.; Kubik, L.; Szczechowicz, R.; Rekosz, J.; Kwiatkowska, D.; Gajek, J.; Mazurek, W.; Kominek, M.; Siminiak, T.; Guzniczak, E.; Carrageta, M.; Monteiro, P.; Providencia, L.; Monteiro, S.; Pinho, T.; Gavina, C.; Sousa, C.; Loureiro, J.; Ferreira, A. R.; Cardoso, A. Almada; Araujo, J. Rodrigues; Rebolo, I.; Catarino, C.; Santos, J. Oliveira; Nunes, L. P.; Mimoso, J.; Marques, N.; Leitao, M. A.; Pais, J.; Fernandes, A.; Diogo, A. Nunes; Nóbrega, J.; Moreira, J. I. Azevedo; Mateus, P.; Oliveira, J.; Selas, M.; Ribeiro, V.; Albuquerque, A.; Reis, R. Palma; Ramos, A.; Salazar, F.; Nair, D.; Ng, C. 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J.; Thorington, S.; Pasquini, J.; Iwaoka, R.; Tannenbaum, M.; Prouty, D.; Wiseman, A.; Sharow, A.; Graham, B.; Ali, M. I.; Dale, H. T.; Tarsi, D.; Picone, M.; Juarez, S.; Hamroff, G.; Hollenweger, L.; Scirica, B.; Sabatine, M.; Marti, J.; Perlman, R.; Pavlides, A.; Joffe, I.; Albirini, A.; Campbell, T.; Puri, S.; Lopez, C.; Pearce, D.; Shah, D.; McPherson, J.; Donegan, R.; Murdock, D.; Block, D.; Malik, A.; Musina, R.; Dauber, I. M.; Varner, C. R.; Bach, R.; Palazzolo, M.; Bhalla, H.; Thompson, M.; Pollock, S.; Johnson, S.; Lipson, L.; Brunk, S.; Karas, S.; Vicari, R.; Kuvin, J.; Mooney, P.; Aycock, G.; Lane, B.; Sharma, M.; Gibson, T.; Chang, G.; DiVito, P.; Mehta, R. H.; Watkins, K.; Chiu, A.; Gunderson, J.; Tedder, B.; Williams, P.; Hage-Korban, E.; Childs, A.; Banerjee, S.; Kazi, F.; Bennett, J.; Barnes, D.; Wohns, D.; Noorman, C.; Aggarwal, K.; Lau-Sickman, A.; Paulowski, J.; Amos, M.; Rider, J.; Fenton, S.; Schantz, M.; Hakas, J.; Mcsorley, J.; Felten, W.; Bitzer, V.; Russell, J.; Loyo, J.; Adjei, A.; Mehta, K.; Uretsky, B.; Hale, M.; Shaikh, S.; Miller, M.; Hollenbaugh, D.; Crawford, K.; Fortuin, D.; Galindo, A.; del Core, M.; Butkus, E.; Collins, J.; Prior, J.; Hahn, R.; Greene-Nashold, J.; Alexander, J.; Genova, E.; MacDonell, A.; Broadwater, S.; Kereiakes, D.; White, D.; Lopez, M.; Schenks, R.; Lui, H.; Gibbons, P.; Davis, B.; Thornton, K.; Daley, P.; Budzon, S.; Mccullum, K.; Delio-Cox, B.; Nadar, V.; Keim, S.; McLaurin, B.; Davis, C. L.; Betzu, R.; Al-Jumaily, J.; Bolli, R.; Alshaher, M.; Leesar, M.; Collins, T.; Akkad, H.; Bilazarian, S.; Marsters, M. Jean; Kennett, J.; Melegrito, K.; Mostel, E.; Harris, R.; Chang, M.; Hatfield, G.; Makam, S.; Garvey, M.; Levite, H.; White, J.; Abdel-Latief, A.; Pelletier, L.; Carr, K.; Mckenna, K.; de Lemos, J.; Soto, G.; Kozina, J.; Harris, D.; Vlastaris, A.; Bittel, B.; Riba, A. L.; Gugudis, J.; Singh, N.; Qureshi, I.; Doty, W.; Lehmann, J.; Lieber, I.; Martin, S.; Nicu, M.; Bhalodkar, N.; Ravi, P.; Canto, J.; Bass, M.; Campbell, C.; Steinhubl, S.; Moles, K.; Harjai, K.; Stapleton, D. D.; Hoey, K.; Erwin, J.; Fikes, W.; Stein, B.; Sabatino, K. C.; Teklinski, A.; Colfer, H.; Ward, P.; Langevin, E.; Faucett, S.; Mamdani, S.; DeSimone, L.; Tuohy, E.; Cullen, T.; Eisenberg, S.; Chronos, N.; ALLEN, R. P.; Erickson, B.; Mahon, K.; Kirby, A.; Siegel, C.; Stroud, L.; Johnson, J.; Panchal, V.; Pearson, A.; Abell, T.; de Gregorio, M.; Boomer, L.; Vahdat, O.; VanNatta, B.; Long, P.; Chalavarya, G.; Skatrud, L.; Carey, C.; Wright, W.; Mechem, C. J.; Matthews, B.; Adams, A.; Vora, K.; Wead, J.; Koren, M.; Gregory, D.; El Khadra, M.; Peacock, G.; Kieval, J.; Barron, M.; Lewis, D.; Grice, R.; Bobek, M.; Moore, C.; Nygaard, T.; Fischell, T.; Salman, W.; Schneider, C.; Muhlestein, B.; Peeler, D.; Chang, D.; Todd, A.; Chilakamarri, V. K.; Hanley, P. C.; Gelormini, J.; Iacona, M. A.; Effron, B.; Mazzurco, S.; Mazzella, M.; Wyman, P.; Orchard, R.; Battin, D.; Rezkalla, S.; Bishop, C.; Sharp, S.; Gredler, F.; Knap, P.; Fadel, M.; Saucedo, J.; Keng, A.; Imburgia, M.; Blank, E.; Effat, M.; Khoury, S.; Mardis, R.; Baldari, D.; Tafuri, L.; Mascolo, R.; Taylor, D.; Mandviwala, M.; Khan, W.; Mumford, T.; Mayer, N.; Mitchell, B.; Oliver, T.; Lombardi, W.; Zimmerman, T.; Rohrbeck, S.; Cooke, L.; Craig, M.; Mego, D.; Griffin, B.; Perez, J.; LeClerc, K.; Addington, J.; Aboufakher, R.; Ahmed, A.; Westecott, B.; Steel, K.; Hawkins, K.; Shah, A.; Ward, U. Sayers; McGreevy, M. J.; Goldberg, R. K.; Prashad, R.; McDonough, C.; Silver, K.; Josephson, R.; Witsaman, S.; Labib, S.; Woodhead, G.; Schrank, J.; Bell, K.; Chandna, H.; Holly, D.; Bethea, C.; Fife, B.; Gruberg, L.; Singer, A.; Ramgadoo, M.; Lalonde, T.; Morin, R.; French, W.; Barillas, O.; Gradner, G.; Kahn, Z.; Gress, J.; Rocco, D.; Thew, S.; Stifter, W.; Fisher, M.; McNamara, J.; Kupfer, J.; Agocha, A.; Cush, S.; Jones, S. R.; Whitaker, T.; Jones, S. E.; Stover, T.; Kumkumian, G.; Kent, K.; Greenberg, A.; Pandey, P.; Pytlewski, G.; Matsumura, M.; Kai, W.; Sameshima, S.; Thomas, J.; MacNicholas, D.; Pillai, K.; Jones, D.; Navas, J. P.; Laskoe, B.; Patel, P.; Fini, G.; Minor, S.; Shipwash, T.; Cabrera-Santamaria, A.; Rivera, E.; Mincher, L.; Jafar, M. Zubair; Yen, M.; Finkle, C.; Rahimtoola, A.; Severson, L.; Labroo, A.; Jinich, D.; Tam, K.; Vogel, C.; Aggarwal, R.; Zakhary, B.; Curtis, S.; Lyster, M.; Humphrey, K.; Lavine, P.; Fujise, K.; Birnbaum, Y.; Allen, J.; Kesselbrenner, M.; Michel, K.; Staniloae, C.; Liu, M. 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M.; Schneider, W. R.; Villa, A.; Desai, V.; Chhabra, A.; Banks, K.; Herzog, W.; Burley, T.; Quyyumi, A.; Smiley, W.; Manocha, P.; Fishbein, G.; Weller, C.; Coffman, A.; Kim, C.; Kedia, A.; Firth, B.; Rizvi, M. Danish; Dahiya, R.; Foster, B.; Balcells, E.; Metzger, D. C.; Lester, J.; Bissett, J.; Fahdi, I.; Sides, E. A.; Azrin, M.; Martin, C.; Quick, A.; Conaway, D. Green; Garg, M.; Schallert, G.; Lancaster, L.; Mckissick, S.; Atieh, M.; Garbarino, J.; Eisenberg, D.; Uusinarkaus, K.; Wirtemburg, P.; Ellis, J.; Cristaldi, J.; Berglund, R.; Negus, B.; Pappas, J.; Rocha, R.; Nguyen, T.; Stone, J.; Janosik, D.; Labovitz, A.; Elmore, N.; Dave, R.; Loffredo, K.; Gabriel, G.; Snyder, C.; Ahmed, O.; Stone, H.; Kelley, M.; Diffenback, M.; Friedman, B.; Zirkle, J.; Severa, L.; Sample, S.; Dignen, K.; Raisinghani, A.; Ben-Yehuda, O.; Ghannadian, B.; Moscoso, R.; Mankowski, J.; Boliek, W. G.; Rukavina, M.; Davis, W.; Ledbetter, S.; Handel, F.; Mastouri, R.; Mahenthiran, J.; Foltz, J.; Malhotra, V.; Jonas, J.; Berk, M.; Singh, V.; Nelson, M.; Elsner, G.; Gall, J.; Kondo, N.; Frank, S.; Chandraratna, P.; Ranasinghe, S.; Ebrahimi, R.; Treadwell, M.; Walters, B.; Hughes, L.; Kramer, J.; Kumar, K.; Mente, T.; Lachterman, B.; Schifferdecker, B.; Munshi, K.; Sease, D.; Waldo, D.; Chandler, G.; Manns, D.; Nahhas, A.; Kamalesh, M.; Williams, V.; Reich, D.; Desalca, M.; Sharma, S.; Liston, M.; Gupta, K.; Costa, M.; Altschuller, A.; Lemmertz, K.; Shanes, J.; Hansen, C.; Therrien, M.; Mendelson, R.; Ramnarine, R.; Myers, G.; Donovan, C.; Klein, M.; Fine, D.; Owens, S.; Murray, C.; Ketroser, R.; Heifetz, S.; Darnell, Z.; Touchon, R.; Taghizadeh, B.; Bohle, D.; Norwood, D.; Forrest, T.; Jackson, S.; Shumate, K.; Bayles, A.; Masroor, M.; North, W. K.; Fishberg, R.; Merveil-Ceneus, B.; Butcher, R.; Menapace, F.; Kilbride, S.; Ramabadran, R. S.; Loukinen, K.; Khalil, J.; Walsh, S.; Gill, S.; Cyncar, R.; McLachlan, J.; Surakanti, V.; Rusterholtz, L.; Shoukfeh, F.; Stephenson, L.; Tsang, M.; Nolan, V.; Gilchrist, I.; Jefferson, D.; Feldman, T.; Reyes, L.; Santos, R.; Little, W.; Wesley, D.; Gharib, W.; Mendell, A.; Esham, G.; Kakavas, P.; Whitcomb, C.; Book, K.; Bazzi, A.; Alvarez, J.; Cohen, Y.; Ayres, T.; Rhule, V.; Labib, A.; Schuler, P.; Zughaib, M.; Telck, K.; Bikkina, M.; Turnbull, K.; Sharma, T.; Orosz, S.; Shah, R.; Petrino, M.; Hughes, M.; Hershey, J.; Hudock, D.; Hui, P.; Von Bakonyi, A.; Arnold, A.; Kappel, D.; Pennock, G.; Cloud, B.; Tucker, K.; Harp, L.; Hoover, C.; Eisenhauer, M.; Roth, J.; Young, C.; Thai, H.; Escalante, A.; Bautista, J.; Gazmuri, R.; Nyland, J.; Cubeddu, L.; DeFranco, A.; Dias, D.; Fielding, M.; Reeves, R.; Hermany, P.; Meissner-Dengler, S.; Evans, M.; Flores, E.; Tannenbaum, A.; McGarr, K.; Moran, J.; Stout, E.; Allred, S. F.; Henderson, D.; Crandall, L.; Strote, J.; Voyles, W.; Robeson, D.; Bedoya, R.; Omar, B.; Pettyjohn, F.; Revere, C.; Coy, K.; Margolis, J.; Sotolongo, C.; Scheffel, M.; Munir, A.; Shirwany, A.; Douglas, L.; Girala, R.; Humphreys, R.; Agarwal, J.; Bankowski, D.; Watson, R.; Bishop, B.; Klementowicz, P.; Blais, D.; Cohen, B.; Lobur, E.; Dimenna, J.; Dempsey, K.; Izzo, M.; Bondi, L.; Carell, E.; Eaton, C.; Saltiel, F.; Grewal, G.; Connolly, T.; Little, T.; Wiegman, P.; Gips, S.; Held, J.; Paraschos, A.; Quesada, R.; White, J. King; Goudreau, E.; Sears, M.; Istfan, P.; Holt, S.; McClung, J.; Nguyen, N.; Quintana, O.; Gottlieb, D.; Knutson, T.; Barringhaus, K.; Lester, F.; Sullivan, P.; Rodriguez-Ospina, L.

    2015-01-01

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

  20. Statins: Are These Cholesterol-Lowering Drugs Right for You?

    Science.gov (United States)

    ... per liter, or mmol/L). Low-density lipoprotein cholesterol (LDL, or "bad" cholesterol) should be below 100 mg/ ... re following the recommended lifestyle behaviors but your cholesterol — particularly your LDL (bad) cholesterol — remains high, statins might be an ...

  1. The dyslipidemia of chronic renal disease: effects of statin therapy

    NARCIS (Netherlands)

    Ozsoy, Riza C.; van Leuven, Sander I.; Kastelein, John J. P.; Arisz, Lambertus; Koopman, Marion G.

    2006-01-01

    PURPOSE OF REVIEW: Dyslipidemia is a prevalent condition in patients with chronic renal disease, but is often left untreated. Statin treatment constitutes an effective way to improve lipid abnormalities. This review summarizes present studies on dyslipidemia and its treatment in patients with

  2. Statins in cardiac surgery | Drummond | Southern African Journal of ...

    African Journals Online (AJOL)

    The outcomes of interest were postoperative mortality, non-fatal myocardial infarction, acute renal injury, cerebrovascular events, and atrial fibrillation. An a priori decision was taken to conduct a subgroup analysis of coronary artery bypass surgery (CABG) and valve replacement surgery. Results: Statins were associated ...

  3. Statin use and risk of nonmelanoma skin cancer

    DEFF Research Database (Denmark)

    Arnspang, S.; Pottegård, A.; Friis, Søren

    2015-01-01

    BACKGROUND: Evidence is conflicting regarding statin use and risk of basal cell (BCC) and squamous cell skin cancer (SCC). METHODS: Using Danish nationwide registries, we identified all patients with incident BCC/SCC during 2005-2009 and matched them to population controls. We computed odds ratios...

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

    African Journals Online (AJOL)

    LW Drummond

    2013-04-02

    Apr 2, 2013 ... (Cochran-Mantel-Haenszel) models were used based on the presence (upper CI of I2 > 25%) or the absence (upper CI of I2 <. 25%) of significant heterogeneity between the studies, respectively. Pooled dichotomous outcomes were reported as the odds ratio (OR) and 95% CI. In the event of statin therapy ...

  5. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

    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, the c...

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

    NARCIS (Netherlands)

    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

  8. Statin use and rupture of abdominal aortic aneurysm

    DEFF Research Database (Denmark)

    Wemmelund, H; Høgh, A; Hundborg, H H

    2014-01-01

    BACKGROUND: Ruptured abdominal aortic aneurysm (rAAA) is associated with high mortality. Research suggests that statins may reduce abdominal aortic aneurysm (AAA) growth and improve rAAA outcomes. However, the clinical impact of statins remains uncertain in relation to both the risk and prognosis...... drug use, co-morbidities, socioeconomic markers, healthcare contacts and death were obtained from Danish nationwide registries. RESULTS: The study included 3584 cases and 3584 matched controls. Current statin use was registered for 418 patients with rAAA (11.7 per cent) and 539 AAA controls (15.0 per...... cent), corresponding to an age- and sex-matched odds ratio (OR) of 0.70 (95 per cent confidence interval (c.i.) 0.60 to 0.81) for rAAA in current statin users versus never users. The decreased risk of rAAA remained after adjustment for potential confounding factors (adjusted OR 0.73, 0.61 to 0...

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

    Directory of Open Access Journals (Sweden)

    Winters Paul

    2010-03-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2017-08-15

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

  12. Impact of diagnostic ECG to wire delay in STEMI patients treated with primary PCI - a DANAMI-3 substudy

    DEFF Research Database (Denmark)

    Nepper-Christensen, Lars; Lønborg, Jacob; Høfsten, Dan Eik

    2018-01-01

    AIMS: We evaluated the impact of delay from diagnostic pre-hospital electrocardiogram (ECG) to wiring of the infarct related vessel (ECG-to-wire) >120 minutes on cardiovascular magnetic resonance (CMR) markers of reperfusion success and clinical outcome in patients with ST-segment elevation...... myocardial infarction (STEMI). METHODS AND RESULTS: We included 1492 patients in the analyses of clinical outcome. CMR was performed in 748 patients to evaluate infarct size and myocardial salvage. In total, 304 patients (20%) had ECG-to-wire >120 minutes, which was associated with larger acute infarct size...... (18% [interquartile range (IQR), 10-28] vs. 15% [8-24]; p=0.022) and smaller myocardial salvage (0.42 [IQR 0.28-0.57] vs. 0.50 [IQR 0.34-0.70]; p=0.002). However, 33% of the patients with ECG-to-wire >120 minutes still had a substantial myocardial salvage of more than 0.50. In a multivariable analysis...

  13. Estatinas na doença renal crônica Statins in chronic renal disease

    Directory of Open Access Journals (Sweden)

    Soraia R. C. Ferreira

    2005-10-01

    Full Text Available Hipertrigliceridemia e o HDL baixo são aspectos comuns em pacientes com insuficiência renal crônica. A mortalidade cardiovascular está substancialmente aumentada na presença de doença renal crônica (10-20 vezes maior. Existem evidências de estudos clínicos com estatinas sugerindo uma ação protetora dessas drogas na progressão da doença renal. Além disso, pacientes pós-transplante renal recebendo fluvastatina, experimentaram redução na incidência de infartos não fatais e de mortalidade cardíaca. Entretanto, um estudo recente com atorvastatina não demonstrou reduções na morbi-mortalidade cardiovascular entre pacientes diabéticos em hemodiálise. Estudos em andamento definirão o preciso papel das estatinas neste grupo especial de pacientes.Hypertriglyceridemia and low HDL-c are common features in patients with chronic renal failure. Cardiovascular mortality is substantially increased in the presence of chronic renal disease (10-20 times higher. There is evidence from clinical trials with statins suggesting their protective role in the progression of renal disease. In addition, reduced rates of non-fatal myocardial infarction and cardiac mortality were seen after renal transplant in patients receiving fluvastatin. However, a recent study with atorvastatin failed to demonstrate reduction in cardiovascular morbidity and mortality among diabetic patients on hemodyalisis therapy. Ongoing trials will define the precise role of statins in this subset of patients.

  14. Changes in Statin Prescription Patterns in Patients Admitted to an Australian Geriatric Subacute Unit.

    Science.gov (United States)

    Noaman, Samer; Al-Mukhtar, Omar; Abramovic, Sheri; Mohammed, Hanin; Goh, Cheng Yee; Long, Claire; Neil, Christopher; Janus, Edward; Cox, Nicholas; Chan, William

    2018-01-31

    Assessment of demographic and clinical factors influencing the decision of statin discontinuation in the elderly population admitted to subacute geriatric unit. The aim of this study is to assess the clinical factors impacting the decision-making process of statin discontinuation in the elderly. We retrospectively assessed changes in statin discontinuation and prescription among patients (≥60 years old) discharged from a geriatric evaluation and management unit by reviewing hospital digital medical records at Western Health - The Williamstown Hospital over a 12-month period from 4 February 2012 until 4 February 2013 inclusive. The main outcome of the study was to determine the independent predictors of statin discontinuation using logistic regression analysis. Of the studied population, 46% were already prescribed statins prior to their admission. Statins were discontinued in 17.5% of patients at discharge. Predictors of statin de-prescription included octogenarian status, primary prevention indication, poor functional recovery, residential care facility discharge destination and lower cognitive function. The presence of previous cardiovascular disease history and the burden of comorbidities were not predictors of statin discontinuation. We observed that factors that conveyed poor prognosis such as advanced age, poor functional recovery, worse cognitive function, being discharged to a residential care facility as well as primary prevention indication for statin prescription are predictors of statin discontinuation in the geriatric unit. Copyright © 2018 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  15. Hepatotoxicity associated with statin use: analysis of the cases included in the Spanish Hepatotoxicity Registry

    Directory of Open Access Journals (Sweden)

    Emilia V. Perdices

    2014-04-01

    Full Text Available Objectives: The hepatotoxic potential of statins is controversial. The objectives of this study were to describe the relative frequency of hepatotoxicity caused by statins and the phenotypes found in Spain. Patients and methods: The incidence of hepatotoxicity attributed to statins in the Spanish Hepatotoxicity Registry (REH were studied and compared with those attributed to other drugs. Results: Between April 1994 and August 2012, the REH included a total of 858 cases of which 47 (5.5 % were attributed to statins. Of these, 16 were due to atorvastatin (34 %; 13 to simvastatin (27.7 %; 12 to fluvastatin (25.5 %; 4 to lovastatin (8.5 % and 2 to pravastatin (4.3 %. Statins represented approximately half of the cardiovascular group which occupied 3.er place (10 %, after anti-infectious agents (37 % and central nervous system drugs (14 %. The hepatocellular pattern was predominant, especially in the simvastatin group (85%, the cholestatic/mixed pattern was more frequent with fluvastatin (66 % and had a similar distribution to atorvastatin. Patients with statin-induced toxicity were older (62 years versus 53 years, p < 0.001 and more often demonstrated an autoimmune hepatitis phenotype (8.5 % versus 1.4 %, p < 0.003. Conclusions: Statins are not a common cause of hepatotoxicity in Spain. Atorvastatin is the statin involved in the greatest number of incidents. The liver injury pattern varies among the different statins. The hepatitis phenotype with autoimmune features appears to be a characteristic signature of statin-induced hepatotoxicity.

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

    Science.gov (United States)

    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.

  17. Association between statin use and physical function among community-dwelling older Japanese adults.

    Science.gov (United States)

    Kawai, Hisashi; Ihara, Kazushige; Kera, Takeshi; Hirano, Hirohiko; Fujiwara, Yoshinori; Tanaka, Masashi; Kojima, Motonaga; Obuchi, Shuichi

    2018-04-01

    Statin-associated muscle symptoms (SAMS) are the muscle-related side-effects of statins, but the association between statin use and physical function among community-dwelling older adults is unclear. The objective of the present study was to examine the association between statin use and physical function among community-dwelling older Japanese adults by considering the risk factors of statin-associated muscle symptoms. The participants were 1022 community-dwelling older adults aged 65-88 years, who participated in comprehensive health checkups from 2013 to 2015. Statin use in the participants (381 men and 559 women) was verified by using data from their medicine notebooks. The differences between statin use (users and non-users) and physical functions (grip strength, knee extension torque, normal and maximum gait speed, Timed Up & Go test, one-legged stance, quadriceps muscle thickness and echo intensity) were analyzed using the t-test. Multiple regression analyses were also carried out to examine the association between statin use and physical function. A total of 93 men (24.4%) and 154 women (27.5%) were statin users. Grip strength, normal gait speed and one-legged stance declined significantly in statin users compared with the non-users. In multiple regression analysis while controlling for the risk factors of statin-associated muscle symptoms, including age, sex, body mass index and number of medicines, no independent association, between statin use and the reduction of physical functions, was observed. Statin use was not associated with the decline of physical function in community-dwelling older Japanese adults. Geriatr Gerontol Int 2018; 18: 623-630. © 2017 Japan Geriatrics Society.

  18. Statin Intolerance and Risk of Coronary Heart Events and All-Cause Mortality Following Myocardial Infarction.

    Science.gov (United States)

    Serban, Maria-Corina; Colantonio, Lisandro D; Manthripragada, Angelika D; Monda, Keri L; Bittner, Vera A; Banach, Maciej; Chen, Ligong; Huang, Lei; Dent, Ricardo; Kent, Shia T; Muntner, Paul; Rosenson, Robert S

    2017-03-21

    Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality. This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy. We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013. Statin intolerance was defined as down-titrating statins and initiating ezetimibe therapy, switching from statins to ezetimibe monotherapy, having International Classification of Diseases, 9th revision, diagnostic codes for rhabdomyolysis or an antihyperlipidemic adverse event, followed by statin down-titration or discontinuation, or switching between ≥3 types of statins within 1 year after initiation. High statin adherence over the year following hospital discharge was defined as proportion of days covered ≥80%. Recurrent MI, CHD events (recurrent MI or a coronary revascularization procedure), and mortality were identified from 1 year after hospital discharge through December 2014. Overall, 1,741 patients (1.65%) had statin intolerance, and 55,567 patients (52.8%) had high statin adherence. Over a median of 1.9 to 2.3 years of follow-up, there were 4,450 recurrent MIs, 6,250 CHD events, and 14,311 deaths. Compared to beneficiaries with high statin adherence, statin intolerance was associated with a 36% higher rate of recurrent MI (41.1 vs. 30.1 per 1,000 person-years, respectively), a 43% higher rate of CHD events (62.5 vs. 43.8 per 1,000 person-years, respectively), and a 15% lower rate of all-cause mortality (79.9 vs. 94.2 per 1,000 person-years, respectively). The multivariate-adjusted hazard ratios (HR) comparing beneficiaries with statin intolerance versus those with high statin adherence were 1.50 (95% confidence interval [CI

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

    Science.gov (United States)

    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

  20. Genetic variation in statin intolerance and a possible protective role for UGT1A1.

    Science.gov (United States)

    V Willrich, Maria Alice; Kaleta, Erin J; Bryant, Sandra C; Spears, Grant M; Train, Laura J; Peterson, Sandra E; Lennon, Vanda A; Kopecky, Stephen L; Baudhuin, Linnea M

    2018-01-01

    The etiology of statin intolerance is hypothesized to be due to genetic variants that impact statin disposition and clearance. We sought to determine whether genetic variants were associated to statin intolerance. The studied cohort consisted of hyperlipidemic participants (n = 90) clinically diagnosed with statin intolerance by a cardiologist and matched controls without statin intolerance. Creatine kinase activity, lipid profiles and genetic analyses were performed on genes involved in statin metabolism and included UGT1A1 and UGT1A3 sequencing and targeted analyses of CYP3A4*22, CYP3A5*3, SLCO1B1*5 and *1b, ABCB1 c.3435C>T, ABCG2 c.421C>A and GATM rs9806699. Although lipids were higher in cases, genetic variant minor allele frequencies were similar between cases and controls, except for UGT1A1*28, which was less prevalent in cases than controls.

  1. Pattern of statin use changes following media coverage of its side effects

    DEFF Research Database (Denmark)

    Kriegbaum, Margit; Liisberg, Kasper Bering; Wallach-Kildemoes, Helle

    2017-01-01

    BACKGROUND: The media plays a role in shaping opinions about medical decisions, for example, whether to initiate or stop treatment. An association between negative media attention and statin discontinuation has been demonstrated, but it may differ depending on the reason for prescription...... and whether the user is new (incident) or long term (prevalent). AIM: The aim of this study is to explore whether a Danish newspaper article featuring the side effects of statins affects statin discontinuation in incident versus prevalent users, with the reason for prescription also taken into account...... discontinuation in all statin users in Denmark in 2007 before the media event (n=343,438) and after it in 2008 (n=404,052). RESULTS: Compared to 2007, statin discontinuation among prevalent users in 2008 increased by 2.97 percentage points (pp). The change in discontinuation varied with the indication for statin...

  2. The therapeutic potential of antioxidants, ER chaperones, NO and H2S donors, and statins for treatment of preeclampsia

    Directory of Open Access Journals (Sweden)

    Tereza eCindrova-Davies

    2014-05-01

    Full Text Available Preeclampsia is a complex multifactorial disease. Placental oxidative stress, a result of deficient spiral artery remodeling, plays an important role in the pathophysiology of preeclampsia. Antiangiogenic factors secreted from malperfused placenta are instrumental in mediating maternal endothelial dysfunction and consequent symptoms of preeclampsia; the mechanism is likely to involve increased ET-1 secretion and reduced NO bioavailability. Therapeutic interventions so far remain only experimental and there is no established remedy for the treatment of preeclampsia. This review concentrates on the evidence for the therapeutic potential of antioxidants, ER chaperones, NO and H2S donors, and statins. These compounds display pleitropic antioxidant, anti-inflammatory, and pro-angiogenic effects in animal and in vitro studies. Although clinical trials on the use of antioxidant vitamins in pregnancy proved largely unsuccessful, the scope for their use still exists given the beneficial cardioprotective effects of antioxidant-rich Mediterranean diet, periconceptual vitamin use and the synergistic effect of vitamin C and l-arginine. Encouraging clinical evidence exists for the use of NO donors, and a clinical trial is underway testing the effect of statins in treatment of preeclampsia. H2S recently emerged as a novel therapeutic agent for cardiovascular disease, and its beneficial effects were also tested in animal models of preeclampsia. It is risky to prescribe any medication to pregnant women on a large scale, and any future therapeutic intervention has to be well tested and safe. Many of the compounds discussed could be potential candidates.

  3. [IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (studie IMPROVE-IT)].

    Science.gov (United States)

    Špinar, Jindřich; Špinarová, Lenka; Vítovec, Jiří

    2014-12-01

    The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) 125 mg/dl. Randomized double blind clinical trial in patients with acute coronary syndrome and low cholesterol level. The simvastatin monotherapy arms LDL-C target was < 70 mg/dl, the comparison arm was simvastatin + ezetimibe. Ezetimibe was assumed to further lower LDL-C by 15 mg/dl and produce an estimated ~ 8 % to 9 % treatment effect. The primary composite end point was CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization ( 30 days postrandomization). The targeted number of events was 5,250. 18,144 patients were enroled with either ST segment elevation MI (STEMI, n = 5,192) or UA/non-ST segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Primary endpoint occured in 2 742 patients (34.7 %) treated with simvastatin in monotherapy and in 2 572 patients (32.7 %) (p = 0.016) treated with combination. Compared to patients with coronary heart disease given the drug simvastatin plus a placebo, those given both simvastatin and the non-statin drug, ezetimibe, had a 6.4 % lower combined risk of subsequent heart attack, stroke, cardiovascular death, rehospitalization for unstable angina and procedures to restore blood flow to the heart. Heart attacks alone were reduced by 13 %, and non-fatal stroke by 20 %. Deaths from cardiovascular disease were statistically the same in both groups. Patients were followed an average of approximately six years, and some as long as 8.5 years. Approximately 2 patients out of every 100 patients treated for 7 years avoided a heart attack or stroke [Number Needed to Treat (NNT

  4. Mood, Personality, and Behavior Changes During Treatment with Statins: A Case Series

    OpenAIRE

    Cham, Stephanie; Koslik, Hayley J.; Golomb, Beatrice A.

    2015-01-01

    Psychiatric adverse drug reactions (ADRs) have been reported with statin use, but the literature regarding statin-associated mood/behavioral changes remains limited. We sought to elicit information germane to natural history and characteristics of central nervous system/behavioral changes in apparent connection with statin and/or cholesterol-lowering drug use, and delineate mechanisms that may bear on an association. Participants (and/or proxies) self-referred with behavioral and/or mood chan...

  5. Statin Adherence and the Risk of Stroke: A Dose-Response Meta-Analysis.

    Science.gov (United States)

    Xu, Tao; Yu, Xinyuan; Ou, Shu; Liu, Xi; Yuan, Jinxian; Chen, Yangmei

    2017-04-01

    Statins are one of the most common medications for stroke prevention. Increasing evidence indicates that the effect of statins against stroke may depend on the optimal adherence of the patients to the long-term therapies. However, the magnitude of the association between statin adherence and the risk of stroke has not been determined. We conducted a dose-response meta-analysis to investigate the association between statin adherence and the risk of stroke. The Medline and Embase databases were systematically searched to identify relevant observational studies that evaluated the association between statin adherence and stroke risk. Statin adherence was primarily quantified by the proportion of days covered by prescribed statins. Studies in which relative risks (RRs) with 95% confidence intervals (CIs) for the association between statin adherence and stroke risk were reported or could be estimated were included in this meta-analysis. A total of 15 studies with 710,504 participants were included. The pooled RR of total stroke for the categories with the highest compared with the lowest adherence to statins was 0.72 (95% CI 0.65-0.79). Stratified by stroke subtype, the pooled RR for ischemic stroke (IS) was 0.83 (95% CI 0.74-0.92) and for hemorrhagic stroke was 0.75 (95% CI 0.51-1.09). The dose-response analysis indicated that an improvement in statin adherence of 20% was associated with an 8% lower risk of total stroke (RR 0.92; 95% CI 0.89-0.94). In the subgroup analysis for IS, an improvement in statin adherence of 20% was associated with a 7% lower risk of IS (RR 0.93; 95% CI 0.88-0.99). Improved adherence to statins was associated with a lower risk of stroke, particularly of IS.

  6. Statin Use and Hospital Length of Stay Among Adults Hospitalized With Community-acquired Pneumonia.

    Science.gov (United States)

    Havers, Fiona; Bramley, Anna M; Finelli, Lyn; Reed, Carrie; Self, Wesley H; Trabue, Christopher; Fakhran, Sherene; Balk, Robert; Courtney, D Mark; Girard, Timothy D; Anderson, Evan J; Grijalva, Carlos G; Edwards, Kathryn M; Wunderink, Richard G; Jain, Seema

    2016-06-15

    Prior retrospective studies suggest that statins may benefit patients with community-acquired pneumonia (CAP) due to antiinflammatory and immunomodulatory effects. However, prospective studies of the impact of statins on CAP outcomes are needed. We determined whether statin use was associated with improved outcomes in adults hospitalized with CAP. Adults aged ≥18 years hospitalized with CAP were prospectively enrolled at 3 hospitals in Chicago, Illinois, and 2 hospitals in Nashville, Tennessee, from January 2010-June 2012. Adults receiving statins before and throughout hospitalization (statin users) were compared with those who did not receive statins (nonusers). Proportional subdistribution hazards models were used to examine the association between statin use and hospital length of stay (LOS). In-hospital mortality was a secondary outcome. We also compared groups matched on propensity score. Of 2016 adults enrolled, 483 (24%) were statin users; 1533 (76%) were nonusers. Statin users were significantly older, had more comorbidities, had more years of education, and were more likely to have health insurance than nonusers. Multivariable regression demonstrated that statin users and nonusers had similar LOS (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], .88-1.12), as did those in the propensity-matched groups (HR, 1.03; 95% CI, .88-1.21). No significant associations were found between statin use and LOS or in-hospital mortality, even when stratified by pneumonia severity. In a large prospective study of adults hospitalized with CAP, we found no evidence to suggest that statin use before and during hospitalization improved LOS or in-hospital mortality. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  7. MICROCIRCULATORY ISCHEMIA AND STATINS: LESSONS OF INTERVENTION CARDIOLOGY

    Directory of Open Access Journals (Sweden)

    An. A. Alexandrov

    2015-12-01

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

  8. Statins do not inhibit the FGFR signaling in chondrocytes

    Czech Academy of Sciences Publication Activity Database

    Fafílek, B.; Hampl, Marek; Říčánková, N.; Veselá, Iva; Bálek, L.; Kunová Bosáková, M.; Gudernová, I.; Vařecha, M.; Buchtová, Marcela; Krejčí, P.

    2017-01-01

    Roč. 25, č. 9 (2017), s. 1522-1530 ISSN 1063-4584 R&D Projects: GA ČR(CZ) GA14-31540S Grant - others:GA MŠk(CZ) LH12004 Institutional support: RVO:67985904 Keywords : statins * FGF signaling * chondrocytes Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Developmental biology Impact factor: 4.742, year: 2016

  9. Ultrasound Diagnosis of Bilateral Quadriceps Tendon Rupture After Statin Use

    Directory of Open Access Journals (Sweden)

    Nesselroade, Ryan D

    2010-09-01

    Full Text Available Simultaneous bilateral quadriceps tendon rupture is a rare injury. We report the case of bilateral quadriceps tendon rupture sustained with minimal force while refereeing a football game. The injury was suspected to be associated with statin use as the patient had no other identifiable risk factors.The diagnosis was confirmed using bedside ultrasound. [West J Emerg Med. 2010; 11(4:306-309.

  10. Ischemic heart disease: effectiveness and safety of statin treatment ...

    African Journals Online (AJOL)

    12 (40). 42 (58). 30 (42). Ethnicity, n (%). Malay. Chinese. Indian. 26 (79). 19 (73). 8 (62). 7 (21). 7 (27). 5 (38). 33 (46). 26 (36). 13 (18). Previous history of IHD, n (%). Yes. No. 35(92). 18(53). 3(8). 16(47). 38(53). 34(47). Table 2: Lipid levels of the study population on admission (N = 72). Lipid levels. Statin users. aP-value.

  11. A novel therapeutic effect of statins on nephrogenic diabetes insipidus

    Science.gov (United States)

    Bonfrate, Leonilde; Procino, Giuseppe; Wang, David Q-H; Svelto, Maria; Portincasa, Piero

    2015-01-01

    Statins competitively inhibit hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase, resulting in reduced plasma total and low-density lipoprotein cholesterol levels. Recently, it has been shown that statins exert additional ‘pleiotropic’ effects by increasing expression levels of the membrane water channels aquaporin 2 (AQP2). AQP2 is localized mainly in the kidney and plays a critical role in determining cellular water content. This additional effect is independent of cholesterol homoeostasis, and depends on depletion of mevalonate-derived intermediates of sterol synthetic pathways, i.e. farnesylpyrophosphate and geranylgeranylpyrophosphate. By up-regulating the expression levels of AQP2, statins increase water reabsorption by the kidney, thus opening up a new avenue in treating patients with nephrogenic diabetes insipidus (NDI), a hereditary disease that yet lacks high-powered and limited side effects therapy. Aspects related to water balance determined by AQP2 in the kidney, as well as standard and novel therapeutic strategies of NDI are discussed. PMID:25594563

  12. [Unmet needs: patients with statin intolerance or familial hypercholesterolemia].

    Science.gov (United States)

    Masana, Luis; Civeira, Fernando

    2016-05-01

    The achievement of low-density lipoprotein (LDL) therapeutic targets is especially difficult in some patients at high cardiovascular risk. These patients include persons with statin intolerance and those with very high LDL cholesterol (LDLc) levels such as persons with familial hypercholesterolemia. The proportion of statin-intolerant patients is between 7% and 29%. Alternative lipid-lowering drugs (including ezetimibe) are less effective and are not free from adverse effects. Both alirocumab, with the ODYSSEY ALTERNATIVE study, and evolocumab, with the GAUSS study, have shown strong lipid-lowering efficacy, with much greater tolerability than currently available alternatives, with the result that a larger number of patients achieve therapeutic targets. In familial hypercholesterolemia, the monogenic metabolic disease most frequently associated with high cardiovascular risk, early intervention is cost-effective. Although statins have substantially improved the prognosis of familial hypercholesterolemia, many affected individuals are far from achieving the recommended therapeutic targets. In this patient group, PCSK9 inhibition with monoclonal antibodies has also been shown to be highly effective in reducing LDLc, especially in heterozygous individuals. The studies performed to date have shown that these drugs are safe and effective and can help many patients with familial hypercholesterolemia to drastically reduce their cardiovascular risk. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Arteriosclerosis. All rights reserved.

  13. Statin related adverse effects and patient education: a study from resource limited settings.

    Science.gov (United States)

    Mulchandani, Rubina; Lyngdoh, Tanica; Chakraborty, Praloy; Kakkar, Ashish Kumar

    2017-11-27

    Statins are the most widely prescribed class of drugs for coronary artery disease (CAD) patients and yet literature on the prevalence of statin related adverse effects (AEs) and gaps in patient education is quite limited especially in resource-limited settings of developing world. The present study was conducted to determine the prevalence of myopathy (muscle ailments) and other statin associated adverse effects among CAD patients on statin therapy. The study also aimed to assess patient perceptions, attitudes and awareness concerning the use of statins. It was a cross-sectional study conducted among 300 adult CAD patients visiting the out-patient department of a tertiary care hospital in North India, who were receiving statins for their diagnosis. An interviewer administered questionnaire was used to collect data on statin use among patients and adverse effects experienced. Myopathy or muscle related ailments like muscle pain, cramps and muscle weakness were the most prevalent (32, 34 and 47%, respectively), followed by numbness, tingling and burning in the extremities (31%). Joint pain and cognitive impairments were seen in nearly 20% of the patients. The level of awareness among participants regarding the use of statins was sub-optimal. Lack of knowledge and under-reporting of adverse effects were major concerns. The study shows that a considerable proportion of statin users experience adverse effects and knowledge and awareness amongst patients is inadequate. Awareness programmes and counselling for patients, sensitisation of healthcare professionals and better screening systems for monitoring AEs can help improve the scenario.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  16. Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists

    Science.gov (United States)

    Di Stasi, Stephanie L.; MacLeod, Toran D.; Winters, Joshua D.

    2010-01-01

    Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy. PMID:20688875

  17. Risk of new-onset diabetes mellitus during treatment with low-dose statins in Japan: A retrospective cohort study.

    Science.gov (United States)

    Kato, S; Miura, M

    2018-02-26

    The risk of new-onset diabetes mellitus (NODM) in Japanese patients using low-dose hydroxymethyl glutaryl coenzyme A reductase inhibitors (statins) has not been previously examined. The aim of this study was to assess the risk of NODM associated with use of high- and low-potency statins in Japanese patients taking low-dose statins. A retrospective cohort study of 2554 Japanese patients who started treatment with a statin was conducted. Only patients taking the same dose of the same statin were enrolled, and patients were separated into high- and low-potency statin groups. The outcome was incidence of NODM during statin treatment. The incidence rate of NODM in the cohort was 7.4% (n = 190). Kaplan-Meier survival curves showed a significantly higher rate of NODM in patients taking high-potency statins compared with those taking low-potency statins (P < .001, log-rank test). Baseline fasting plasma glucose levels, use of high-potency statins, male gender and combination treatment with calcium channel blockers, immunosuppressants or steroids were identified as factors that significantly increased the risk for NODM using Cox proportional hazard regression analysis. The use of high-potency statins at a low standard daily dose significantly increased the risk of NODM in Japanese patients compared with low-potency statins. Furthermore, clinicians should also be careful when prescribing statins in combination with steroids or immunosuppressants due to the increased risk of NODM. © 2018 John Wiley & Sons Ltd.

  18. NEW POSSIBILITIES OF STATIN THERAPY IN ARTERIAL HYPERTENSION

    Directory of Open Access Journals (Sweden)

    E. M. Khurs

    2010-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2012-01-01

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

  1. Enhanced Impact of Cholesterol Absorption Marker on New Atherosclerotic Lesion Progression After Coronary Intervention During Statin Therapy.

    Science.gov (United States)

    Mori, Kenta; Ishida, Tatsuro; Tsuda, Shigeyasu; Oshita, Toshihiko; Shinohara, Masakazu; Hara, Tetsuya; Irino, Yasuhiro; Toh, Ryuji; Hirata, Ken-Ichi

    2017-02-01

    Clinical trials suggest that residual risks remain for coronary artery disease (CAD) during low-density lipoprotein cholesterol (LDL-C) lowering therapy. We aimed to investigate the role of exogenous lipids in the prognosis of CAD after percutaneous coronary intervention (PCI). A total of 145 patients with CAD, who underwent elective PCI, and 82 non-CAD (control) patients were enrolled in this study. CAD patients underwent follow-up coronary angiography 6-9 months after PCI, and were classified into three groups: 1) patients who showed in-stent restenosis (ISR) in the original stented segment, 2) patients with other non-target coronary atherosclerotic lesions (de novo), and 3) patients with neither ISR nor a de novo lesion. Biochemical analyses were performed on fasting serum samples at the time of follow-up coronary angiography. Despite the controlled serum LDL-C levels, CAD patients with statin showed elevated cholesterol absorption marker campesterol/total cholesterol (TC), synthesis marker lathosterol/TC, campesterol/lathosterol ratio, and apolipoprotein B48 (apoB48) concentration compared with non-CAD patients. The high campesterol/TC, campesterol/lathosterol ratio, and apoB48 concentration were associated with de novo lesion progression after PCI. In stepwise multivariate logistic regression analysis, campesterol/TC and apoB48 concentrations were independent risk factors for de novo lesion progression in statin-treated CAD patients after PCI. The increase of cholesterol absorption marker and apoB48 concentration may lead to the progression of de novo lesions, and these markers may represent a residual risk during statin treatment after PCI.

  2. Impact of Acute Hyperglycemia on Myocardial Infarct Size, Area at Risk, and Salvage in Patients With STEMI and the Association With Exenatide Treatment

    DEFF Research Database (Denmark)

    Lønborg, Jacob; Vejlstrup, Niels; Kelbæk, Henning

    2014-01-01

    and infarct size adjusting for area at risk did not differ between the groups. Treatment with exenatide resulted in increased salvage index both among patients with normoglycemia and hyperglycemia. Thus, we conclude that the association between hyperglycemia upon hospital admission and infarct size in STEMI...... patients is a consequence of a larger myocardial area at risk but not of a reduction in myocardial salvage. Also, cardioprotection by exenatide treatment is independent of glucose levels at hospital admission. Thus, hyperglycemia does not influence the effect of the reperfusion treatment but rather...

  3. Reduced Risk of Barrett's Esophagus in Statin Users: Case-Control Study and Meta-Analysis.

    Science.gov (United States)

    Beales, Ian L P; Dearman, Leanne; Vardi, Inna; Loke, Yoon

    2016-01-01

    Use of statins has been associated with a reduced incidence of esophageal adenocarcinoma in population-based studies. However there are few studies examining statin use and the development of Barrett's esophagus. The purpose of this study was to examine the association between statin use and the presence of Barrett's esophagus in patients having their first gastroscopy. We have performed a case-control study comparing statin use between patients with, and without, an incident diagnosis of non-dysplastic Barrett's esophagus. Male Barrett's cases (134) were compared to 268 male age-matched controls in each of two control groups (erosive gastro-esophageal reflux and dyspepsia without significant upper gastrointestinal disease). Risk factor and drug exposure were established using standardised interviews. Logistic regression was used to compare statin exposure and correct for confounding factors. We performed a meta-analysis pooling our results with three other case-control studies. Regular statin use was associated with a significantly lower incidence of Barrett's esophagus compared to the combined control groups [adjusted OR 0.62 (95 % confidence intervals 0.37-0.93)]. This effect was more marked in combined statin plus aspirin users [adjusted OR 0.43 (95 % CI 0.21-0.89)]. The inverse association between statin or statin plus aspirin use and risk of Barrett's was significantly greater with longer duration of use. Meta-analysis of pooled data (1098 Barrett's, 2085 controls) showed that statin use was significantly associated with a reduced risk of Barrett's esophagus [pooled adjusted OR 0.63 (95 % CI 0.51-0.77)]. Statin use is associated with a reduced incidence of a new diagnosis of Barrett's esophagus.

  4. Statins and Musculoskeletal Conditions in U.S. Air Force Active Duty Service Members.

    Science.gov (United States)

    Tvaryanas, Anthony P; Wagner, Joseph H; Maupin, Genny M; Schroeder, Valarie M

    2017-09-01

    This study examined the association of statin use and musculoskeletal conditions in statin users and nonusers within the population of U.S. Air Force active duty Service members in the military health care system. The study was a retrospective cohort analysis of Service members between 2004 and 2014 as identified from personnel data having physical fitness and cardiac risk data available and who were free of musculoskeletal diagnoses for 6 months before the study period. Based on pharmacy data, participants were divided into two groups: statin users (received a statin for at least 90 days) and nonusers (never received a statin throughout the study period). Using participants' baseline characteristics, a propensity score was generated and used to match statin users to nonusers in a 1:3 ratio. Conditional logistic regression was used to determine the odds ratio (OR) for a musculoskeletal injury. A total of 123,138 participants met study criteria (592 statin users and 122,546 nonusers). Of these, 516 statin users were propensity score matched to 1,548 nonusers. Among matched pairs, statin users had a higher OR (OR: 1.369; 95% confidence interval [CI]: 1.166-1.606) for musculoskeletal conditions. This association was driven by a higher frequency of back problems in statin users relative to nonusers. The number needed to be exposed for one additional person to be harmed was 20.104 (95% CI: 10.326-232.711). Statin use was associated with an increased likelihood of musculoskeletal conditions in the population of U.S. Air Force active duty Service members. Further investigations should evaluate the contribution of duty-related physical requirements as well as the duration of musculoskeletal condition-associated duty limitations. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

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

    Science.gov (United States)

    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.

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

    DEFF Research Database (Denmark)

    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...... 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......, only 62% were using statins at the end of follow up. The chance of ever receiving statins was lowest if not initiated within 180-days following the first purchase of GLM (OR 0.75, 95% CI 0.74-0.76). A previous myocardial infarction was associated with increased statin treatment (OR 4.51; 95% CI 4...

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

    LENUS (Irish Health Repository)

    2011-04-01

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

  8. The stats are in: an update on statin use in COPD

    Directory of Open Access Journals (Sweden)

    Carlson AA

    2015-10-01

    Full Text Available Alexa A Carlson,1 Ethan A Smith,2 Debra J Reid11Department of Pharmacy and Health System Sciences, School of Pharmacy, Northeastern University, Boston, MA, USA; 2Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA, USAAbstract: COPD is a chronic inflammatory disease of the lungs associated with an abnormal inflammatory response to noxious particles, the most prevalent of which is cigarette smoke. Studies have demonstrated that cigarette smoking is associated with activation of the bone marrow, and chronic smoking can lead to the inflammatory changes seen in COPD. Due to the inflammatory nature of the disease, medications affecting the inflammatory pathway may have clinical benefit and are being evaluated. One such class of medications, HMG-CoA reductase inhibitors, have been evaluated in the COPD population. Early studies have suggested that HMG-CoA reductase inhibitors have a variety of benefits in COPD including improvements in inflammatory markers, exacerbation rates, and mortality rates. However, the majority of this data comes from retrospective cohort studies, suggesting the need for randomized controlled trials. Recently, two randomized controlled trials, STATCOPE and RODEO, evaluated the benefit of HMG-CoA reductase inhibitors in the COPD population and found no benefit in exacerbation rates and vascular or pulmonary function, respectively. These results are reflected in practice guidelines, which do not support the use of HMG-CoA reductase inhibitors for the purpose of reducing COPD exacerbations.Keywords: chronic obstructive pulmonary disease, statins, HMG-CoA reductase inhibitors

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

    Science.gov (United States)

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

    2017-06-17

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

  10. Statin Therapy and Mortality in HIV-Infected Individuals; A Danish Nationwide Population-Based Cohort Study

    DEFF Research Database (Denmark)

    Rasmussen, Line; Kronborg, Gitte; Larsen, Carsten

    2013-01-01

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

  11. Trials

    Directory of Open Access Journals (Sweden)

    Michele Fornaro

    2010-01-01

    Full Text Available Mental Retardation (MR is a developmental disability characterized by impairments in adaptive daily life skills and difficulties in social and interpersonal functioning. Since multiple causes may contribute to MR, associated clinical pictures may vary accordingly. Nevertheless, when psychiatric disorders as Treatment Resistant Depression (TRD and/or alcohol abuse co-exist, their proper detection and management is often troublesome, essentially due to a limited vocabulary MR people could use to describe their symptoms, feelings and concerns, and the lack of reliable screening tools. Furthermore, MR people are among the most medicated subjects, with (over prescription of antidepressants and/or typical antipsychotics being the rule rather than exception. Thus, treatment resistance or even worsening of depression, constitute frequent occurrences. This report describes the case of a person with MR who failed to respond to repetitive trials of antidepressant monotherapies, finally recovering using aripiprazole to fluvoxamine augmentation upon consideration of a putative bipolar diathesis for “agitated” TRD. Although further controlled investigations are needed to assess a putative bipolar diathesis in some cases of MR associated to TRD, prudence is advised in the long-term prescription of antidepressant monotherapies in such conditions.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We perform...

  14. Reduced risk of decompensation and death associated with use of statins in patients with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Bang, U C; Benfield, T; Bendtsen, F

    2017-01-01

    with alcoholic cirrhosis were identified and 5417 were eligible for matching. The mean age was 56 (SD 10) years and 36% were females. The prevalence of use of statins was 15%. We included 744 in the matched cohort. Mortality rates were 88 (95% CI 73-105) per 1000 years for patients using statin and 127 (95% CI......BACKGROUND: Reports have indicated that the use of statins may ameliorate the course of cirrhosis. AIM: To determine the relationship between use of statins and mortality rate in patients with cirrhosis. METHODS: We did a retrospective case-cohort analysis based on data from the Danish registers...... from the period 1995 through 2014. Index date was time of diagnosis of cirrhosis (ICD-10: K703) and cohort entry depended on whether the patient was statin user or not. We used propensity score matching with a statin:non-statin ratio of 1:2. We included the exposure to statins (ATC classification C10AA...

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

    DEFF Research Database (Denmark)

    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....

  16. Statin adherence and treatment LDL-cholesterol response in type 2 diabetes patients

    NARCIS (Netherlands)

    De Vries, Dianna; Voorham, Jaco; Hak, Eelko; Denig, Petra

    2014-01-01

    Background: In clinical practice statins are not optimally used and lipid targets are not achieved in at least a third of the patients. This lack of treatment response could be due to undertreatment (low-dose statin) and low adherence to treatment. Objectives: To determine the relationship between

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

    NARCIS (Netherlands)

    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

  18. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

    Energy Technology Data Exchange (ETDEWEB)

    Sirvent, P., E-mail: pascal.sirvent@univ-bpclermont.fr [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France); Clermont Université, Université Blaise Pascal, EA 3533, Laboratoire des Adaptations Métaboliques à l' Exercice en conditions Physiologiques et Pathologiques (AME2P), BP 80026, F-63171 Aubière cedex (France); Fabre, O.; Bordenave, S. [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France); Hillaire-Buys, D. [CHRU Montpellier, 34295 Montpellier (France); Raynaud De Mauverger, E.; Lacampagne, A.; Mercier, J. [U1046, INSERM, Université Montpellier 1 and Université Montpellier 2, 34295 Montpellier (France); CHRU Montpellier, 34295 Montpellier (France)

    2012-03-01

    The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dysfunction of calcium homeostasis in human and rat healthy muscle samples. We thus evaluated in the present study, mitochondrial function and calcium signaling in muscles of patients treated with statins, who present or not muscle symptoms, by oxygraphy and recording of calcium sparks, respectively. Patients treated with statins showed impairment of mitochondrial respiration that involved mainly the complex I of the respiratory chain and altered frequency and amplitude of calcium sparks. The muscle problems observed in statin-treated patients appear thus to be related to impairment of mitochondrial function and muscle calcium homeostasis, confirming the results we previously reported in vitro. -- Highlights: ► The most common and problematic side effect of statins is myopathy. ► Patients treated with statins showed impairment of mitochondrial respiration. ► Statins-treated patients showed altered frequency and amplitude of calcium sparks.

  19. Muscle mitochondrial metabolism and calcium signaling impairment in patients treated with statins

    DEFF Research Database (Denmark)

    Sirvent, P; Fabre, Odile Martine Julie; Bordenave, S

    2012-01-01

    The most common and problematic side effect of statins is myopathy. To date, the patho-physiological mechanisms of statin myotoxicity are still not clearly understood. In previous studies, we showed that acute application in vitro of simvastatin caused impairment of mitochondrial function and dys...

  20. Association between statin use and Bell's palsy: a population-based study.

    Science.gov (United States)

    Hung, Shih-Han; Wang, Li-Hsuan; Lin, Herng-Ching; Chung, Shiu-Dong

    2014-09-01

    Several reports mention that statin (HMG-CoA reductase inhibitor) use seems to be associated with several neurologic disorders and that the lipid-lowering effect of statins may contribute to some neural toxicity. This study aimed to evaluate the association between statin use and Bell's palsy using a population-based health insurance database. This case-control study identified 1,977 subjects with Bell's palsy as cases and 5,931 sex- and age-matched subjects without Bell's palsy as controls from the Taiwan Longitudinal Health Insurance Database 2000. Conditional logistic regressions was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for previous use of statins between the cases and controls. The associations of regular and irregular statin users with Bell's palsy were further analyzed. By Chi-square test, there was a significant difference in the prevalence of statin use between cases and controls (23.2 vs. 16.4%, p Bell's palsy was significantly associated with previous regular statin use (≥60 days within 6 months) (adjusted OR: 1.46, 95% CI 1.28-1.67). However, there was no increased adjusted OR of irregular statin use (Bell's palsy.

  1. Statin Drugs Markedly Inhibit Testosterone Production by Rat Leydig Cells In Vitro: Implications for Men

    Science.gov (United States)

    Statin drugs lower blood cholesterol by inhibiting hepatic 3-hydroxy-3-methylglutaryl-Coenzyme-A reductase. During drug development it was shown that statins inhibit production of cholesterol in the testis. We evaluated testosterone production in vitro, using highly purified rat ...

  2. The association between statin use and risk of age-related macular degeneration

    Science.gov (United States)

    Ma, Le; Wang, Yafeng; Du, Junhui; Wang, Mingxu; Zhang, Rui; Fu, Yihao

    2015-01-01

    The aim of the present study was to evaluate the association between statin use and the risk of age-related macular degeneration (AMD). A systematic search of the PubMed, EMBASE and ISI web of science databases was used to identify eligible published literatures without language restrictions up to April 2015. Summary relative ratios (RRs) and 95% CIs were estimated using a fixed-effect or random-effects model. A total of 14 studies met the inclusion criteria and were included in this meta-analysis. No significant association was observed between statin use and the risk of any AMD (RR, 0.95; 95% CI, 0.74–1.15); and stratified analysis showed that statins had a significantly different effects on early and late stages of AMD. For early AMD, statin use significantly reduced the risk approximately 17% (RR, 0.83; 95% CI, 0.66–0.99). At the late stage, we observed a significant protective association of statin use with exudative AMD (RR, 0.90; 95% CI, 0.80–0.99), in contrast with the absent association between statins and geographic atrophy (RR, 1.16; 95% CI, 0.77–1.56). These results demonstrated that statin use was protective for early and exudative AMD. Additional large prospective cohort studies and RCTs are required to determine the potential effect of statins on AMD prevention. PMID:26658620

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-15

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

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

    Science.gov (United States)

    Bosomworth, N John

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

  6. Statin Use and Functional Outcome after Tissue Plasminogen Activator Treatment in Acute Ischaemic Stroke

    NARCIS (Netherlands)

    Miedema, I; Uyttenboogaart, M; Koopman, K; De Keyser, J; Luijckx, G J

    Background: Preliminary findings suggest that statins may have a neuroprotective effect in patients with acute ischaemic stroke. This study investigated whether patients prior on statin therapy and treated with tissue plasminogen activator (tPA) for acute ischaemic stroke have a better functional

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  8. Statin treatment and reduced risk of pneumonia in patients with diabetes

    NARCIS (Netherlands)

    van de Garde, E M W; Hak, E; Souverein, P C; Hoes, A W; van den Bosch, J M M; Leufkens, H G M

    2006-01-01

    BACKGROUND: Recent prognostic studies have shown that previous treatment with statins is associated with a better outcome in patients admitted to hospital with pneumonia. Because of an increased risk of pneumonia in patients with diabetes, we assessed the effects of statin use on the occurrence of

  9. The pharmaco-economics of peri-operative beta-blocker and statin ...

    African Journals Online (AJOL)

    We conducted a pharmaco-economic analysis of the prospective peri-operative studies of beta-blocker and statin administration for major elective non-cardiac surgery, using the Discovery Health claims costs for 2004. This analysis shows that acute peri-operative beta-blockade and statin therapy could result in a cost ...

  10. Statin use after acute myocardial infarction: a nationwide study in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Jeppe Nørgaard; Gislason, Gunnar H; Abildstrom, Steen Z

    2005-01-01

    AIMS: To study outpatient statin use after first acute myocardial infarction (AMI) in Denmark between 1995 and 2002 and to determine the predictors of statin use. METHODS: This is a nationwide population-based study using administrative registries. Patients with first AMI between 1995 and 2002 ol...

  11. Association of Medicare Part D medication out-of-pocket costs with utilization of statin medications.

    Science.gov (United States)

    Karaca-Mandic, Pinar; Swenson, Tami; Abraham, Jean M; Kane, Robert L

    2013-08-01

    To examine the association between statin out-of-pocket (OOP) costs and utilization among the Medicare Part D population. 2006-2008 administrative claims and enrollment data for the 5 percent Medicare sample. Sample included 346,583 beneficiary-year observations of statin users enrolled in stand-alone prescription drug plans, excluding low-income subsidy recipients. We estimated the association between a plan's OOP statin costs and statin utilization using an instrumental variable approach to account for potential bias due to plan selection. Adherence was defined as percentage of days covered (PDC) of at least 80 percent. Plan OOP costs were constructed for a representative market basket of statin medications. Analyses controlled for demographic characteristics, cardiovascular disease risk, co-morbidity presence, and regional characteristics. About 67 percent of the sample had a PDC of at least 80 percent. An increase in annual statin OOP from $200 (50th percentile) to $240 (75th percentile) was associated with a reduction in the rate of adherent beneficiaries from 67 percent to 56 percent (p < .001). Greater OOP costs for statins are associated with reductions in statin utilization. © Health Research and Educational Trust.

  12. A genetic risk score is associated with statin-induced low-density lipoprotein cholesterol lowering

    NARCIS (Netherlands)

    Leusink, Maarten; Maitland-van der Zee, Anke H.; Ding, Bo; Drenos, Fotios; van Iperen, Erik Pa; Warren, Helen R.; Caulfield, Mark J.; Cupples, L. Adrienne; Cushman, Mary; Hingorani, Aroon D.; Hoogeveen, Ron C.; Hovingh, G. Kees; Kumari, Meena; Lange, Leslie A.; Munroe, Patricia B.; Nyberg, Fredrik; Schreiner, Pamela J.; Sivapalaratnam, Suthesh; de Bakker, Paul Iw; de Boer, Anthonius; Keating, Brendan J.; Asselbergs, Folkert W.; Onland-Moret, N. Charlotte

    2016-01-01

    To find new genetic loci associated with statin response, and to investigate the association of a genetic risk score (GRS) with this outcome. In a discovery meta-analysis (five studies, 1991 individuals), we investigated the effects of approximately 50000 single nucleotide polymorphisms on statin

  13. The antiplatelet effect of clopidogrel is not attenuated by statin treatment in stable patients with ischemic heart disease

    DEFF Research Database (Denmark)

    Vinholt, Pernille Just; Poulsen, Tina Svenstrup; Korsholm, Lars

    2005-01-01

    Recent studies suggest that cytochrome P450 (CYP) 3A4 metabolized statins attenuate the antiaggregatory effect of clopidogrel. We evaluated how CYP3A4 metabolized statins and non-CYP3A4 metabolized statins influence platelet aggregation when given concomitantly with clopidogrel. Sixty-six stable ...

  14. Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy A Meta-analysis

    NARCIS (Netherlands)

    Preiss, David; Seshasai, Sreenivasa Rao Kondapally; Welsh, Paul; Murphy, Sabina A.; Ho, Jennifer E.; Waters, David D.; Demicco, David A.; Barter, Philip; Cannon, Christopher P.; Sabatine, Marc S.; Braunwald, Eugene; Kastelein, John J. P.; de Lemos, James A.; Blazing, Michael A.; Pedersen, Terje R.; Tikkanen, Matti J.; Sattar, Naveed; Ray, Kausik K.

    2011-01-01

    Context A recent meta-analysis demonstrated that statin therapy is associated with excess risk of developing diabetes mellitus. Objective To investigate whether intensive-dose statin therapy is associated with increased risk of new-onset diabetes compared with moderate-dose statin therapy. Data

  15. Survival of resuscitated cardiac arrest patients with ST-elevation myocardial infarction (STEMI) conveyed directly to a Heart Attack Centre by ambulance clinicians.

    Science.gov (United States)

    Fothergill, Rachael T; Watson, Lynne R; Virdi, Gurkamal K; Moore, Fionna P; Whitbread, Mark

    2014-01-01

    This study reports survival outcomes for patients resuscitated from out-of-hospital cardiac arrest (OHCA) subsequent to ST-elevation myocardial infarction (STEMI), and who were conveyed directly by ambulance clinicians to a specialist Heart Attack Centre for expert cardiology assessment, angiography and possible percutaneous coronary intervention (PCI). This is a retrospective descriptive review of data sourced from the London Ambulance Service's OHCA registry over a one-year period. We observed excellent survival rates for our cohort of patients with 66% of patients surviving to be discharged from hospital, the majority of whom were still alive after one year. Those who survived tended to be younger, to have had a witnessed arrest in a public place with an initial cardiac rhythm of VF/VT, and to have been transported to the specialist centre more quickly than those who did not. A system allowing ambulance clinicians to autonomously convey OHCA STEMI patients who achieve a return of spontaneous circulation directly to a Heart Attack Centre is highly effective and yields excellent survival outcomes. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. A tale of two cities: STEMI interventions in developed and developing countries and the potential of telemedicine to reduce disparities in care.

    Science.gov (United States)

    Mehta, Sameer; Botelho, Roberto; Rodriguez, Daniel; Fernández, Francisco J; Ossa, Maria M; Zhang, Tracy; Kostela, Jennifer C; Reynbakh, Olga; Falcão, Breno; Velásquez, Alicia Henao; Oliveros, Estefania; Pena, Camilo

    2014-04-01

    To utilize telemedicine as a foundation platform for creating population-based STEMI networks. Disparate acute myocardial infarction (AMI) management occurs in developed and developing countries on account of differences in infrastructure resources. As a result, developed countries utilize primary percutaneous coronary intervention (PCI) and second- and third-generation thrombolytic therapy, in contrast to developing countries, which primarily rely on earlier-generation thrombolytic therapy and basic medical management. Reducing the vast gap in AMI care between developed and developing countries is an abysmally slow process. Remote access, telemedicine IT platforms, expert EKG interpretation, teleconsultation, and a strict quality assurance process are incorporated into a population-based AMI network. Lumen Americas Telemedicine Infarct Network (LATIN) is an applied hub-and-spoke strategy, which creates a telemedicine-based STEMI management network across large populations. Primary PCI with targeted door-to-balloon times is the preferred strategy for the hub sites. Telemedicine-guided accurate EKG interpretation and teleconsultation are applied at the spoke sites. An integrated IT platform is used to navigate an effective prehospital triage system. The pilot phase has created 100 LATIN sites in Brazil and Colombia. Telemedicine provides an attractive strategy to reduce the gaps that presently exist in managing AMI in developed and developing countries. © 2014, Wiley Periodicals, Inc.

  17. Trends in statin consumption and cardiovascular mortality in Croatia 2004-2012.

    Science.gov (United States)

    Vojvodić, Zeljko; Stimac, Danijela

    2014-12-01

    Prescribing of statins showed an increasing trend in all developed countries, during the last two decades. The aim of this study was to research the trends in statin consumption in the period from 2004 to 2012 as well as trends of cardiovascular mortality during the 1990 to 2012 period, and to compare them between Croatia and several neighbouring countries. Data on statin expenditures and consumption expresed in defined daily doses per 1000 inhabitants per day (DDD/TID), were taken from annual reports of Croatian Agency for Medicinal Products and Medical Devices (HALMED). Data on crude mortality rates and standardized cardiovascular mortality rates, were taken from the Croatian Health Statistics Yearbooks. The utilization of statins increased by 196.7% during the observed period, with the highest consumption of atorvastatin and simvastatin. Financial expenditure of statins expanded at much faster rate in comparison with overall drug costs. Cardiovascular mortality rates decreased slightly, while maintaining higher level in comparison with some neighbouring countries.

  18. Statin Use Is Associated with Reduced Mortality in Patients with Interstitial Lung Disease

    DEFF Research Database (Denmark)

    Vedel-Krogh, Signe; Nielsen, Sune F; Nordestgaard, Børge G

    2015-01-01

    INTRODUCTION: We hypothesized that statin use begun before the diagnosis of interstitial lung disease is associated with reduced mortality. METHODS: We studied all patients diagnosed with interstitial lung disease in the entire Danish population from 1995 through 2009, comparing statin use versus...... no statin use in a nested 1:2 matched study. RESULTS: The cumulative survival as a function of follow-up time from the date of diagnosis of interstitial lung disease (n = 1,786 + 3,572) and idiopathic lung fibrosis (n = 261 + 522) was higher for statin users versus never users (log-rank: P = 7 · 10......(-9) and P = 0.05). The median survival time in patients with interstitial lung disease was 3.3 years in statin users and 2.1 years in never users. Corresponding values in patients with idiopathic lung fibrosis were 3.4 versus 2.4 years. After multivariable adjustment, the hazard ratio for all...

  19. Protective Capacity of Statins during Pneumonia Is Dependent on Etiological Agent and Obesity

    Directory of Open Access Journals (Sweden)

    Erik A. Karlsson

    2018-02-01

    Full Text Available Acute respiratory infections are a leading cause of death worldwide. Clinical data is conflicted regarding whether statins improve outcomes for pneumonia. Potential confounding factors including specific etiology of pneumonia as well as obesity could potentially mask protective benefit. Obesity is a risk factor for high cholesterol, the main target for statin therapy. We demonstrate that statin intervention conferred no protective benefit in the context of wild-type mice regardless of infectious agent. Statin intervention conferred either a protective benefit, during influenza infection, or detrimental effect, in the case of pneumococcal infection, in obese animals. These data suggest etiology of pneumonia in the context of obesity could be dramatically altered by the protective effects of statin therapy during bacterial and viral pneumonia.

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

    Directory of Open Access Journals (Sweden)

    Jozić Tanja L.

    2014-01-01

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

  1. Redesigning TRACER trial after TRITON.

    Science.gov (United States)

    Serebruany, Victor L

    2015-10-15

    Designing of smart clinical trials is critical for regulatory approval and future drug utilization. Importantly, trial design should be reconsidered if the interim analyses suggest unexpected harm, or conflicting results were yielded from the other trials within the same therapeutic area. With regard to antiplatelet agents, the perfect example is redesigning of the ongoing PRoFESS trial by eliminating aspirin from clopidogrel arm after the earlier MATCH trial results became available. The goal was to aseess the unchanged TRACER trial design in light of the evidence yielded from the earlier completed TRITON trial. TRACER was designed as a triple versus dual antiplatelet trial in NSTEMI patients with no previous long-term outcome data supporting such aggressive strategy. TRITON data represented dual versus dual antiplatelet therapy, and became available before TRACER enrollment starts revealing prasugrel front-loaded early vascular benefit predominantly in STEMI patients with the growing over time bleeding and cancer risks. Moreover, large prasugrel NSTEMI TRITON cohort exhibited trend towards excess mortality in experimental arm warning against aggressive TRACER design. The long-term TRITON results in general, and especially in the NSTEMI patients challenge unchanged TRACER trial design. Applying dual, rather than triple antiplatelet therapy protocol modification should be considered in TRACER to minimize bleeding, cancer, and non-cardiovascular death risks. Copyright © 2015. Published by Elsevier Ireland Ltd.

  2. The Cost-Benefit Balance of Statins in Hawai'i: A Moving Target.

    Science.gov (United States)

    Lum, Corey J; Nakagawa, Kazuma; Shohet, Ralph V; Seto, Todd B; Taira, Deborah A

    2017-04-01

    Statins are lipid-lowering medications used for primary and secondary prevention of atherosclerotic disease and represent a substantial portion of drug costs in the United States. A better understanding of prescribing patterns and drug costs should lead to more rational utilization and help constrain health care expenditures in the United States. The 2013 Medicare Provider Utilization and Payment Data: Part D Prescriber Public Use File for the State of Hawai'i was analyzed. The number of prescriptions for statins, total annual cost, and daily cost were calculated by prescriber specialty and drug. Potential savings from substituting the highest-cost statin with lower-cost statins were calculated. Over 421,000 prescriptions for statins were provided to Medicare Part D beneficiaries in Hawai'i in 2013, which cost $17.6M. The three most commonly prescribed statins were simvastatin (33.4%), atorvastatin (33.4%), and lovastatin (13.9%). Although rosuvastatin comprised 5.4% of the total statin prescriptions, it represented 30.1% of the total cost of statins due to a higher daily cost ($5.53/day) compared to simvastatin ($0.25/day) and atorvastatin ($1.10/day). Cardiologists and general practitioners prescribed the highest percentage of rosuvastatin (8% each). Hypothetical substitution of rosuvastatin would have resulted in substantial annual cost savings (Simvastatin would have saved $1.3M for 25% substitution and $5.1M for 100% substitution, while atorvastatin would have saved $1.1M for 25% substitution and $4.3M for 100% substitution). Among Medicare Part D beneficiaries in Hawai'i, prescribing variation for statins between specialties were observed. Substitution of higher-cost with lower-cost statins may lead to substantial cost savings.

  3. Statin Therapy in Low-Risk Air Force Aviators with Isolated Hypercholesterolemia.

    Science.gov (United States)

    Tvaryanas, Anthony P; Mahaney, Heather J; Schroeder, Valarie M; Maupin, Genny M

    2017-08-01

    This study evaluated the use of statin therapy in U.S. Air Force (USAF) aviators with isolated hypercholesterolemia in terms of compliance with clinical practice guidelines (CPGs) and effectiveness in reducing low-density lipoprotein cholesterol (LDL-C) and coronary heart disease (CHD) risk. This was a mixed design, 8-yr retrospective study that included 8185 participants with isolated hypercholesterolemia, of which 1458 (17.81%) were prescribed statin monotherapy. Overall agreement between CPG recommendations and patient-clinician decision makers was 0.920 (95% confidence interval: 0.955, 0.959) and 0.891 (95% confidence interval: 0.843, 0.851) per 2002 and 2013 CPGs, respectively. Overall agreement was primarily driven by the negative proportion of specific agreement; positive agreement was moderate for the 2002 CPG and poor for the 2013 CPG. LDL-C levels marginally decreased for all participants except non-CPG-recommended statin users per the 2002 CPG. CHD risk was minimally reduced for all participants per the 2002 CPG with the exception of CPG-recommended statin users, for whom risk increased; CHD risk decreased for CPG-recommended statin users, but increased for non-CPG-recommended statin users per the 2013 CPG. No one statin medication was found to be more clinically effective in reducing LDL-C or CHD risk, regardless of dose intensity. Aerospace medicine practitioners are following CPG recommendations for statin therapy. Statins provided minimal benefit, however, and CPG recommendations proved irrelevant in reducing LDL-C and CHD risk in this population of Air Force aviators. This result is attributable, in part, to the young age of the study cohort and the short follow-up period.Tvaryanas AP, Mahaney HJ, Schroeder VM, Maupin GM. Statin therapy in low-risk air force aviators with isolated hypercholesterolemia. Aerosp Med Hum Perform. 2017; 88(8):752-759.

  4. Social stratification in the dissemination of statins after stroke in Sweden.

    Science.gov (United States)

    Sjölander, Maria; Eriksson, Marie; Glader, Eva-Lotta

    2013-05-01

    Since 2005, statins have been recommended to patients with ischaemic stroke. The objective of this study was to analyse how statin treatment has been disseminated in different patient groups (age, sex, socioeconomic status and country of birth) in Sweden between 2004 and 2009. The Swedish Stroke Register (Riks-Stroke) has been linked to the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Approximately 85 % of stroke patients in Sweden are included in Riks-Stroke. Odds ratios for statin prescribing were calculated using a multivariable logistic regression model including age, sex, socioeconomic status and risk factors. During the study period, 108,950 ischaemic stroke patients were discharged alive from hospital. The proportion with statins at discharge increased from 32.9 % in 2004 to 60.1 % in 2009. Patients with secondary school or university education had slightly higher odds [odds ratio (OR) 1.07, 95 % confidence interval (CI) 1.04-1.11 and OR 1.05, 95 % CI 1.01-1.10 respectively] than patients with primary school education. Patients on a high income were prescribed more statins than those on a low income (OR 1.24, 95 % CI 1.19-1.28). Compared with patients born in Sweden, patients born in other countries were prescribed more statins (Nordic countries excepting Sweden: OR 1.07, 95 % CI 1.01-1.14; Europe: OR 1.31, 95 % CI 1.22-1.40; Outside Europe: OR 1.20, 95 % CI 1.08-1.34). Statin prescribing after ischaemic stroke has increased from 2004 to 2009. Our results also show a social stratification in the dissemination of statins, with patients having a higher income and patients with higher education receiving statins more often than those with a lower income and education, and patients born in Sweden receiving statins less often than those born outside of Sweden.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

  7. Inception and deprescribing of statins in people aged over 80 years: cohort study.

    Science.gov (United States)

    Gulliford, Martin; Ravindrarajah, Rathi; Hamada, Shota; Jackson, Stephen; Charlton, Judith

    2017-11-01

    statin use over the age of 80 years is weakly evidence-based. This study aimed to estimate rates of statin inception and deprescribing by frailty level in people aged 80 years or older. a cohort of 212,566 participants aged ≥80 years was sampled from the UK Clinical Practice Research Datalink. Statin inception was defined as a first-ever prescription in a non-statin user; deprescribing was defined as a last ever statin prescription more than 6 months before the end of participant records. Rates were estimated in a time-to-event framework allowing for mortality as a competing risk. Co-variates were age, gender, frailty category and prevention type. prevalent statin use increased from 2001-5 (9.9%) to 2011-15 (49.3%). Inception of statins in never-users was low overall at 2.4% per year (95% confidence interval (CI) 2.2-2.6%) and declined with age. Deprescribing of statins in current users occurred at a rate of 5.6% (95% CI 5.4-5.9%) per year overall and increased with age, reaching 17.8% per year (95% CI 6.7-28.9%) among centenarians. Deprescribing was slightly higher for primary prevention (6.5% per year) than secondary prevention (5.2% per year) indications (P < 0.001). Deprescribing increased with frailty level being 5.0% per year in 'fit' participants and 7.1% in 'severe' frailty (P < 0.001). statin use has increased in the over 80s but deprescribing is common and increases with age and frailty level. These paradoxical findings highlight a need for better evidence to inform statin use and discontinuation for people aged ≥80 years. © The Author 2017. Published by Oxford University Press on behalf of the British Geriatrics Society.All rights reserved. For permissions, please email: journals.permissions@oup.com

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Science.gov (United States)

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

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

  11. 3-Hydroxyl-3-methylglutaryl Coenzyme A (HMG-CoA) Reductase Inhibitor (Statin)-induced 28-kDa Interleukin-1β Interferes with Mature IL-1β Signaling*

    Science.gov (United States)

    Davaro, Facundo; Forde, Sorcha D.; Garfield, Mark; Jiang, Zhaozhao; Halmen, Kristen; Tamburro, Nelsy Depaula; Kurt-Jones, Evelyn; Fitzgerald, Katherine A.; Golenbock, Douglas T.; Wang, Donghai

    2014-01-01

    Multiple clinical trials have shown that the 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors known as statins have anti-inflammatory effects. However, the underlying molecular mechanism remains unclear. The proinflammatory cytokine interleukin-1β (IL-1β) is synthesized as a non-active precursor. The 31-kDa pro-IL-1β is processed into the 17-kDa active form by caspase-1-activating inflammasomes. Here, we report a novel signaling pathway induced by statins, which leads to processing of pro-IL-1β into an intermediate 28-kDa form. This statin-induced IL-1β processing is independent of caspase-1- activating inflammasomes. The 28-kDa form of IL-1β cannot activate interleukin-1 receptor-1 (IL1R1) to signal inflammatory responses. Instead, it interferes with mature IL-1β signaling through IL-1R1 and therefore may dampen inflammatory responses initiated by mature IL-1β. These results may provide new clues to explain the anti-inflammatory effects of statins. PMID:24790079

  12. [Are treatments with statins that are considered unsuitable really unsuitable?].

    Science.gov (United States)

    Estrada Alifonso, Cinta; Vilaseca Canals, Jordi; Méndez Trías, M Ángeles; Lozano Ovalle, Silvia; Jusmet Miquel, Javier; Torres Machado, Victoria; Castro Rivera, Esteban

    2015-01-01

    In the Catalonian Institute of health there are 2 well-established circumstances for indicating lipid-lowering drug treatment with statins in the primary prevention of ischaemic heart disease. These are, severe hypercholesterolaemia, with a low density lipoprotein cholesterol equal to or greater than 240mg/dL, or above 130mg/dL when the coronary risk is equal to or greater than 10% at 10 years. There are data that suggest that these 2 criteria are not the only ones used in routine clinical practice, as such that the majority of patients to whom it is indicated, do not meet either of these 2 conditions. This study aims to determine the characteristics of the patients when statins are indicated outside the aforementioned circumstances. It is concluded that around 40% of patients have clinical characteristics that could justify the treatment. The level of suitability could not be established in about 33% of the patients, due to not being able to determine the coronary risk. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  13. Effect of Metformin on Renal Function After Primary Percutaneous Coronary Intervention in Patients Without Diabetes Presenting with ST-elevation Myocardial Infarction : Data from the GIPS-III Trial

    NARCIS (Netherlands)

    Posma, Rene A.; Lexis, Chris P. H.; Lipsic, Erik; Nijsten, Maarten W. N.; Damman, Kevin; Touw, Daan J.; van Veldhuisen, Dirk Jan; van der Harst, Pim; van der Horst, Iwan C. C.

    2015-01-01

    The association between metformin use and renal function needs further to be elucidated since data are insufficient whether metformin affects renal function in higher risk populations such as after ST-elevation myocardial infarction (STEMI). We studied 379 patients included in the GIPS-III trial in

  14. When do paediatric patients with familial hypercholesterolemia need statin therapy?

    Science.gov (United States)

    Hennig, Matylda; Brandt, Agnieszka; Bautembach-Minkowska, Joanna; Świętoń, Dominik; Mickiewicz, Agnieszka; Chmara, Magdalenia; Wasąg, Bartosz; Kamińska, Ewa; Balcerska, Anna; Limon, Janusz; Rynkiewicz, Andrzej; Gruchała, Marcin; Myśliwiec, Małgorzata

    Familial hypercholesterolemia (FH) is one of the most common autosomal dominant disorders. It is characterized by elevated LDL cholesterol levels occurring already by early childhood. Awareness of health risks in FH patients should incite health professionals to actively seek and treat children with lipid disorders to reduce their risk of myocardial infarction and stroke. The aim of the study was to evaluate the suitability of taking into account the following parameters: ApoB/ApoA index, IMT and e-tracking examination, when initiating statin therapy in FH patients. Materials and methods The study included 57 male and female patients aged 9.57±3.2 years (ranging from 1 year to 17 years), diagnosed with familial hypercholesterolemia confirmed by molecular testing. All the participants had their lipid profile, ApoA and ApoB levels determined. Carotid intima-media thickness (IMT) was measured by carotid ultrasound and arterial stiffness was assessed by e-tracking. The dietary treatment efficacy was monitored in 40 patients and the 12-month combination treatment efficacy in 27 patients. The study was conducted prospectively and retrospectively. Statistical analysis was performed with the EPIINFO Ver. 7.1.1.14 statistical software package. Patients with familial hypercholesterolemia had high mean levels of total cholesterol and LDL cholesterol (287±67 mg/dL and 213±73 mg/dL respectively). 34.37% of the study subjects had a markedly increased ApoB/ApoA index. On IMT or e-tracking examination all the subjects (100%) had vascular abnormalities. After 6 months of a low-cholesterol diet, the mean total and LDL cholesterol levels in the serum had been reduced by 7.2% and 6.2%, respectively. Statins in an average dose of 10.42±2.49 mg daily were prescribed to 36 patients. After one year of the statin therapy, the average serum total and LDL cholesterol levels were 203.5±34.8 mg/dL and 139.1±32.1 mg/dL, respectively, and were still above the target values. Moreover, side

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

    Science.gov (United States)

    Gotoh, Saki; Negishi, Masahiko

    2015-09-22

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

  16. Are the effects of drugs to prevent and to treat heart failure always concordant? The statin paradox and its implications for understanding the actions of antidiabetic medications.

    Science.gov (United States)

    Packer, Milton

    2018-03-22

    Most treatments for chronic heart failure are effective both in preventing its onset and reducing its progression. However, statins prevent the development of heart failure, but they do not decrease morbidity and mortality in those with established heart failure. This apparent discordance cannot be explained by an effect to prevent interval myocardial infarctions. Instead, it seems that the disease that statins were preventing in trials of patients with a metabolic disorder was different from the disease that they were treating in trials of chronic heart failure. The most common phenotype of heart failure in patients with obesity and diabetes is heart failure with a preserved ejection fraction (HFpEF). In this disorder, the anti-inflammatory effects of statins might ameliorate myocardial fibrosis and cardiac filling abnormalities, but these actions may have little relevance to patients with heart failure and a reduced ejection fraction (HFrEF), whose primary derangement is cardiomyocyte loss and stretch. These distinctions may explain why statins were ineffective in trials that focused on HFrEF, but have been reported to produce with favourable effects in observational studies of HFpEF. Similarly, selective cytokine antagonists were ineffective in HFrEF, but have been associated with benefits in HFpEF. These observations may have important implications for our understanding of the effects of antihyperglycaemic medications. Glucagon-like peptide-1 receptor agonists have had neutral effects on heart failure events in people at risk for HFpEF, but have exerted deleterious actions in HFrEF. Similarly, sodium-glucose co-transporter 2 inhibitors, which exert anti-inflammatory effects and reduce heart failure events in patients who are prone to HFpEF, may not be effective in HFrEF. The distinctions between HFrEF and HFpEF may explain why the effects of drugs on heart failure events in diabetes trials may not be relevant to their use in patients with systolic dysfunction

  17. Impact of Statins on Influenza Vaccine Effectiveness Against Medically Attended Acute Respiratory Illness.

    Science.gov (United States)

    Omer, Saad B; Phadke, Varun K; Bednarczyk, Robert A; Chamberlain, Allison T; Brosseau, Jennifer L; Orenstein, Walter A

    2016-04-15

    Statins have antiinflammatory effects that may impact vaccine-induced immune responses. We investigated the impact of statin therapy on influenza vaccine effectiveness (VE) against medically attended acute respiratory illness (MAARI). We conducted a retrospective cohort study over nine influenza seasons using research databases of a large managed care organization in the United States. Influenza vaccination and statin prescription statuses of cohort members and MAARI cases were ascertained on a per-season basis. Incidence rate ratios (IRRs) of MAARI were estimated using Poisson regression and stratified by statin use. Using a ratio of ratios approach, we compared IRRs from periods during to IRRs from periods before influenza circulation and then used relative IRRs to compute VE. After adjustment for multiple prespecified covariates, the influenza VE against MAARI was lower among statin users than nonusers during periods of local (14.1% vs 22.9%; mean difference, 11.4%; 95% confidence interval [CI], -1.7% to 26.1%) and widespread (12.6% vs 26.2%; mean difference, 18.4%; 95% CI, 2.9%-36.2%) influenza circulation. In this study, statin therapy was associated with reduced influenza VE against MAARI. Since many cases of MAARI are not caused by influenza, studies of the impact of statins on influenza VE against laboratory-confirmed influenza are needed. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2016-04-01

    Statins have been linked with improved prostate cancer survival and lower risk of recurrence in men treated with radiation therapy. However, the association is unclear for surgically-treated men. We studied the risk of prostate cancer recurrence and death by statin usage after radical prostatectomy in a cohort of prostate cancer patients treated with radical prostatectomy. A cohort of 1,314 men who underwent curative-intent radical prostatectomy at the Tampere University Hospital, Tampere, Finland during 1995-2009 were linked to national prescription database to obtain detailed information on statin purchases. The risk of PSA recurrence and death (overall and prostate cancer-specific) by statin use before and after the surgery were evaluated using Cox regression with model adjustment for tumor characteristics, total cholesterol and simultaneous use of antidiabetic and antihypertensive drugs. Tissue expression of putative prognostic markers were measured from a subgroup of 323 men. During the median follow-up of 8.6 years after surgery 484 men recurred, while 244 men died (32 due to prostate cancer). In general