title: Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials.
abstract: BACKGROUND
  Our objective was to estimate the comparative harms of individual statins using both placebo-controlled and active-comparator trials.
  
  
  RESULTS
  We systematically reviewed randomized trials evaluating different statins in participants with and without cardiovascular disease. We performed random-effects pairwise and network meta-analyses to quantify the relative harms of individual statins. We included 55 two-armed placebo-controlled and 80 two- or multiarmed active-comparator trials including 246,955 individuals. According to pairwise meta-analyses, individual statins were not different than control in terms of myalgia, creatine kinase elevation, cancer, and discontinuations because of adverse events. Statins as a class resulted in significantly higher odds of diabetes mellitus (odds ratio, 1.09; 95% confidence interval, 1.02-1.16) and transaminase elevations (odds ratio, 1.51; 95% confidence interval, 1.24-1.84) compared with control. When individual statins were compared in network meta-analyses, there were numerous statistically detectable differences, favoring simvastatin and pravastatin. According to dose-level comparisons, individual statins resulted in higher odds of discontinuations with higher doses of atorvastatin and rosuvastatin. Similarly, higher doses of atorvasatin, fluvastatin, lovastatin, and simvastatin were associated with higher odds of transaminase elevations. Simvastatin at its highest doses was associated with creatine kinase elevations (odds ratio, 4.14; 95% credible interval, 1.08-16.24). Meta-regression analyses adjusting for study-level age at baseline, low-density lipoprotein cholesterol level, and publication year did not explain heterogeneity. There was no detectable inconsistency in the network.
  
  
  CONCLUSIONS
  As a class, adverse events associated with statin therapy are not common. Statins are not associated with cancer risk but do result in a higher odds of diabetes mellitus. Among individual statins, simvastatin and pravastatin seem safer and more tolerable than other statins.
authors.affiliation: LSE Health, London School of Economics and Political Science, London, United Kingdom. h.naci@lse.ac.uk
authors.forename: Huseyin
authors.initials: H
authors.lastname: Naci
authors.forename: Jasper
authors.initials: J
authors.lastname: Brugts
authors.forename: Tony
authors.initials: T
authors.lastname: Ades
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D019317:Evidence-Based Medicine; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008055:Lipids / Q000097:blood; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids
keywords: Hydroxymethylglutaryl-CoA Reductase Inhibitors; adverse effects; cardiovascular agents; cardiovascular disease; coronary disease; meta-analysis; statins