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The Medical Journal of Australia Feb 2016To systematically review the evidence on whether statin therapy, commonly used in clinical practice to treat hypercholesterolaemia for primary and secondary prevention... (Review)
Review
OBJECTIVES
To systematically review the evidence on whether statin therapy, commonly used in clinical practice to treat hypercholesterolaemia for primary and secondary prevention of cardiovascular disease, contributes to tendinopathy; and to examine causality according to the Bradford Hill criteria.
STUDY DESIGN
A systematic review of studies examining the relationship between statin therapy and tendinopathy. Included studies were rated based on their methodological quality. A best evidence synthesis was used to summarise the results, and Bradford Hill criteria were used to assess causation.
DATA SOURCES
Ovid MEDLINE, CINAHL Plus, PubMed and Embase databases.
STUDY SELECTION
We included adult human studies published in the English language between January 1966 and October 2015. Study designs eligible for inclusion were randomised controlled trials and cross-sectional, cohort or case-control studies.
DATA SYNTHESIS
Four studies (three cohort studies and one case-control study) were included, with a mean methodological quality score of 67%. Three studies were deemed high quality. Tendon rupture was the primary outcome in three studies, and rotator cuff disease in the other. All studies found no positive association between statin therapy and tendon rupture for the total study population. There was evidence that simvastatin reduces the risk of tendinopathy.
CONCLUSION
To date, there is a paucity of evidence to implicate statin therapy as a well established risk factor or causal mechanism for tendon rupture in the general population. There is strong evidence that simvastatin reduces the risk of tendinopathy.
Topics: Evidence-Based Medicine; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Randomized Controlled Trials as Topic; Risk Factors; Rupture; Tendinopathy
PubMed: 26866552
DOI: 10.5694/mja15.00806 -
Herz Sep 2020The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The VOYAGER meta-analysis reported on the low-density lipoprotein cholesterol (LDL-C)-lowering effect of commonly used statins in Caucasian subjects. As there is limited literature available on the efficacy of statins in Asian populations, the current meta-analysis compared the effects of rosuvastatin and atorvastatin on LDL-C levels in an East Asian population.
METHODS
The MEDLINE, PubMed, Embase, Cochrane Library, and Web of Science databases were searched for randomized controlled trials comparing lipid-lowering effects of rosuvastatin and atorvastatin in an East Asian population. Data on the study design, participant characteristics, and outcomes were extracted. Odds ratios (OR), weighted mean differences (WMD), or standardized mean differences were calculated using the random-effects model.
RESULTS
The meta-analysis comprised 16 randomized controlled trials with 5930 participants. Compared with atorvastatin, patients treated with rosuvastatin had a significant reduction in LDL-C: WMD = -7.15 mg/dl (95% confidence intervals [CI]: -10.71--3.60) mg/dl, p < 0.0001. Meta-regression analyses revealed no significant association between the superior benefits of rosuvastatin and other variables including age, sex, baseline LDL-C level, and follow-up duration. Additionally, the rosuvastatin group of patients, who were treated with half the dose of atorvastatin, achieved a significantly greater reduction in LDL-C levels (WMD = -3.57; 95% CI: -5.40--1.74 mg/dl, p < 0.001). Both rosuvastatin and atorvastatin were well tolerated, with similar incidences of adverse events.
CONCLUSION
Similar to the VOYAGER meta-analysis, which reported a greater efficacy of rosuvastatin in comparison with atorvastatin and simvastatin in Caucasian patients, we found that the efficacy of rosuvastatin was superior to atorvastatin in East Asian patients with hypercholesterolemia.
Topics: Atorvastatin; Cholesterol, LDL; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Rosuvastatin Calcium; Treatment Outcome
PubMed: 30483816
DOI: 10.1007/s00059-018-4767-2 -
Endocrine Mar 2023Statin intolerance is a key barrier to the effective prevention of atherosclerotic cardiovascular disease (ASCVD). Experts do not agree on what it is and how to respond... (Review)
Review
BACKGROUND
Statin intolerance is a key barrier to the effective prevention of atherosclerotic cardiovascular disease (ASCVD). Experts do not agree on what it is and how to respond to this problem clinically.
OBJECTIVE
To characterize the range of expert recommendations about the care of patients with statin intolerance.
METHODS
Systematic review registered in PROSPERO that searched on April 1 2022 in PubMed, EMBASE, Scopus, Cochrane, online textbooks, and specialty textbooks for expert reviews (e.g., review articles and book chapters), systematic reviews, or clinical practice guidelines published in the past 5 years without language restriction. Authors working in duplicate extracted definitions, management recommendations, and supportive evidence cited.
RESULTS
We identified 26 eligible articles, none of which described a systematic method to summarize the evidence or to develop and grade recommendations. Of these, 14 (54%) offered a definition of statin intolerance. A sequenced approach to management of statin intolerance was suggested in 24 (92%) articles describing 12 different approaches without supporting evidence of efficacy. Investigating for other causes was the most common first step. All authors suggested rechallenging after a washout period with either the same or other statin. Few considered nonlipid approaches to reducing ASCVD risk and none recommended involving patients in shared decision making.
CONCLUSION
We found substantial variability in the definition and management of statin intolerance among experts. Few focused on ASCVD risk reduction and none promoted the participation of patients in shared decision making about how to address the threat of ASCVD with or without statins.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Diseases; Atherosclerosis
PubMed: 36459335
DOI: 10.1007/s12020-022-03263-w -
Journal of Affective Disorders May 2014Statin use has been associated with depression; however studies of the association between statin use and depression have yielded mixed results. (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Statin use has been associated with depression; however studies of the association between statin use and depression have yielded mixed results.
OBJECTIVE
To determine whether statin use is associated with depression and to evaluate the evidence supporting this association.
DATA SOURCES
Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, EMBASE, PsycInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched through December 28, 2012.
STUDY SELECTION
We included studies that evaluated exposure to statins, reported the development of depression, and relative risks or odds ratios (ORs) or provided data for their estimation. Two reviewers screened 981 abstracts independently using a standardized form, reviewed full text of 59 selected articles, and included 7 studies in this metaanalysis.
DATA EXTRACTION AND SYNTHESIS
Study design, statin exposure, development of depression, and study quality were extracted by 2 independent reviewers. A pooled OR with 95% confidence interval (CI) was estimated using the random-effects model and heterogeneity was assessed using Cochran's Q test and the I(2) statistic.
RESULTS
Seven observational studies (4 cohort, 2 nested case-control, and 1 cross-sectional) from 5 countries enrolling 9187 patients were included. Statin users were 32% less likely to develop depression than nonusers (adjusted OR, 0.68; 95% CI, 0.52-0.89). Modest heterogeneity was observed between the studies (I(2)=55%, P=0.01), which could be accounted for by one study, exclusion of which removed the heterogeneity (P=0.40, I(2)=2%) and further strengthened the antidepressant effect of statin (adjusted OR, 0.63; 95% CI, 0.43-0.93). Heterogeneity could not be explained by study design or study population. The quality of supporting evidence was fair.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis suggests that statin use is associated with lower risk for depression. However, higher-quality studies are needed to confirm the magnitude of this association.
Topics: Depression; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 24370264
DOI: 10.1016/j.jad.2013.11.026 -
Journal of the American Heart... Mar 2017Cataracts are the main cause of poor vision and blindness worldwide. The effects of statin administration on cataracts remain debated. Therefore, we conducted a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cataracts are the main cause of poor vision and blindness worldwide. The effects of statin administration on cataracts remain debated. Therefore, we conducted a systematic review and meta-analysis to determine whether statin use affects the risk of cataracts.
METHODS AND RESULTS
We performed a systematic search of the electronic databases PubMed, EMBASE, and the Cochrane Library through January 2016. Weighted averages were reported as relative risk values with 95% CIs. Statistical heterogeneity scores were assessed with the standard Cochran's Q test and the I statistic. A total of 6 cohort studies, 6 case-control studies, and 5 randomized controlled trials, together involving more than 313 200 patients, were included in our study. The pooled estimates of cohort studies indicated that the use of statins moderately increases the risk of cataracts (relative risk, 1.13; 95% CI, 1.01-1.25). The pooled estimates of case-control studies (relative risk=1.10, 95% CI, 0.99-1.23) and randomized controlled trials (relative risk, 0.89; 95% CI, 0.72-1.10) indicated that the use of statins does not increase the risk of cataracts. The sensitivity analysis confirmed the stability of the results. Heterogeneity was found among the cohort and case-control studies.
CONCLUSIONS
Based on the present meta-analysis of these studies, we could only conclude that there is no clear evidence showing that statin use increases the risk of cataracts. The most likely case is that there is no association between statin use and cataracts. Because of the considerable benefits of statins in cardiovascular patients, this issue should not deter their use.
Topics: Cataract; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Risk Factors
PubMed: 28320745
DOI: 10.1161/JAHA.116.004180 -
Nature Communications Sep 2021Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from... (Meta-Analysis)
Meta-Analysis
Development of cholesteryl ester transfer protein (CETP) inhibitors for coronary heart disease (CHD) has yet to deliver licensed medicines. To distinguish compound from drug target failure, we compared evidence from clinical trials and drug target Mendelian randomization of CETP protein concentration, comparing this to Mendelian randomization of proprotein convertase subtilisin/kexin type 9 (PCSK9). We show that previous failures of CETP inhibitors are likely compound related, as illustrated by significant degrees of between-compound heterogeneity in effects on lipids, blood pressure, and clinical outcomes observed in trials. On-target CETP inhibition, assessed through Mendelian randomization, is expected to reduce the risk of CHD, heart failure, diabetes, and chronic kidney disease, while increasing the risk of age-related macular degeneration. In contrast, lower PCSK9 concentration is anticipated to decrease the risk of CHD, heart failure, atrial fibrillation, chronic kidney disease, multiple sclerosis, and stroke, while potentially increasing the risk of Alzheimer's disease and asthma. Due to distinct effects on lipoprotein metabolite profiles, joint inhibition of CETP and PCSK9 may provide added benefit. In conclusion, we provide genetic evidence that CETP is an effective target for CHD prevention but with a potential on-target adverse effect on age-related macular degeneration.
Topics: Amides; Anticholesteremic Agents; Benzodiazepines; Cardiovascular Diseases; Cholesterol Ester Transfer Proteins; Coronary Disease; Esters; Humans; Mendelian Randomization Analysis; Oxazolidinones; Quinolines; Sulfhydryl Compounds
PubMed: 34561430
DOI: 10.1038/s41467-021-25703-3 -
Lipids in Health and Disease May 2023Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs).
METHODS
We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted.
RESULTS
Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation.
CONCLUSION
Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Fenofibrate; PCSK9 Inhibitors; COVID-19; Randomized Controlled Trials as Topic; Hypolipidemic Agents; Fatty Acids, Omega-3; Proprotein Convertase 9; Observational Studies as Topic
PubMed: 37158917
DOI: 10.1186/s12944-023-01828-w -
In Vivo (Athens, Greece) 2020Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive... (Review)
Review
BACKGROUND/AIM
Lipid-lowering drugs have been suggested to affect neurocognitive function. This review aimed to give the latest evidence on the way these agents affect neurocognitive function based on clinical trials.
MATERIALS AND METHODS
A systematic search concerning original studies from 2015 to 2020 was performed through the databases PubMed, EMBASE and Cochrane, according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. The trials enrolled numerous patients and were conducted in different areas of the world. The terms used are cholesterol, lipid-lowering drugs, statins and cognitive function.
RESULTS
Eleven randomized trials met the inclusion criteria. The trials included patients suffering from cardiovascular conditions. In particular, patients with coronary heart disease, coronary heart disease risk equivalents and hypercholesterolemia were tested. The trials included evolocumab, alirocumab, statin, ezetimibe or placebo.
CONCLUSION
Lipid-lowering drugs seem to have no significant effect on neurocognitive function, but further research specifically focused on this matter is needed.
Topics: Anticholesteremic Agents; Cholesterol; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Pharmaceutical Preparations
PubMed: 33144414
DOI: 10.21873/invivo.12144 -
Circulation Jun 2019
2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Topics: Anticholesteremic Agents; Biomarkers; Cardiology; Cardiovascular Diseases; Cholesterol; Consensus; Evidence-Based Medicine; Humans; Hyperlipidemias; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 30565953
DOI: 10.1161/CIR.0000000000000624 -
Journal of Medical Virology Jun 2023This systematic review and meta-analysis aimed to determine the efficacy of statins in hospitalized patients with coronavirus disease-2019 (COVID-19). A systematic... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to determine the efficacy of statins in hospitalized patients with coronavirus disease-2019 (COVID-19). A systematic search was made of PubMed, Embase, Cochrane Library, and clinicaltrials.gov, without language restrictions. Randomized controlled trials (RCTs) on treatment of COVID-19 with statins, compared with placebo or standard of care, were reviewed. Seven RCTs (enrolling 1830 participants) met the inclusion criteria. There was no statistically significant difference in all-cause mortality (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.75-1.13), length of hospital stay (weighted mean difference: -0.21 days, 95% CI: -1.01 to 0.59 days), intensive care unit (ICU) admission (RR: 1.84, 95% CI: 0.45-7.55), and mechanical ventilation (RR: 1.09, 95% CI: 0.70-1.70) between the two groups. Statins failed to reduce mortality, ICU admission, mechanical ventilation, and length of stay in hospitalized patients with COVID-19. Statins probably should not be used routinely in COVID-19 patients.
Topics: Humans; COVID-19; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Intensive Care Units; Respiration, Artificial
PubMed: 37254831
DOI: 10.1002/jmv.28823