title: Dose-comparative effects of different statins on serum lipid levels: a network meta-analysis of 256,827 individuals in 181 randomized controlled trials.
abstract: OBJECTIVE
  The extent to which individual statins vary in terms of their impact on serum lipid levels has been studied mainly on the basis of placebo-controlled trials. Our objective was to review and quantify the dose-comparative effects of different statins on serum lipid levels using both placebo- and active-comparator trials.
  
  
  METHODS
  We systematically reviewed randomized trials evaluating different statins in participants with, or at risk of developing, cardiovascular disease. We performed random-effects Bayesian network meta-analyses to quantify the the relative potency of individual statins across all possible dose combinations using both direct and indirect evidence. Dose-comparative effects were determined by estimating the mean change from baseline in serum lipids as compared to control treatment. (systematic review registration: PROSPERO 2011:CRD42011001470).
  
  
  RESULTS
  We included 181 placebo-controlled and active-comparator trials including 256,827 individuals. There were 83 two-armed placebo-controlled trials and the remaining 98 were two- or multi-armed active-comparator trials. All statins reduced serum LDL and total cholesterol levels: higher doses resulted in higher reductions in pretreatment LDL and total cholesterol concentrations. In absolute terms, all statins significantly reduced LDL cholesterol levels as compared to control treatment from average baseline levels of approximately 150 mg/dl, except for fluvastatin at ≤20 mg/day and lovastatin at ≤10 mg/day. Atorvastatin, rosuvastatin, and simvastatin were broadly equivalent in terms of their LDL cholesterol-lowering effects. Dose-comparative effects of indivudual statins were not different between those with and without coronary heart disease at baseline. According to meta-regression analyses, LDL cholesterol-lowering effects of individual statins were not impacted by differences across trials in terms of baseline mean age and proportion of women as trial participants. Pretreatment LDL cholesterol concentrations had a marginally statistically significant effect on LDL cholesterol change from baseline. Mean differences from baseline in HDL cholesterol as compared to control treatment was not significant for any statin-dose combination.
  
  
  CONCLUSIONS
  The findings of this comprehensive review provide supporting evidence for the dose-response relationship of statins in reducing LDL and total cholesterol. The LDL cholesterol-reducing effects of some statins appear less pronounced than the findings of previous meta-analyses, which is particularly the case for the high-dose formulations of atorvastatin and rosuvastatin. The most consistent evidence for a combined reduction in both LDL and total cholesterol was achieved with atorvastatin at >40 mg/day, rosuvastatin at >10 mg/day, and simvastatin at >40 mg/day, which appear equivalent in terms of their LDL and total cholesterol-reducing effects.
authors.affiliation: Department of Social Policy, London School of Economics & Political Science, London, UK. h.naci@lse.ac.uk
authors.forename: Huseyin
authors.initials: H
authors.lastname: Naci
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Brugts
authors.forename: Rachael
authors.initials: R
authors.lastname: Fleurence
authors.forename: A E
authors.initials: AE
authors.lastname: Ades
mesh_terms: D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D019317:Evidence-Based Medicine; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008055:Lipids / Q000097:blood*; D008390:Markov Chains; D009010:Monte Carlo Method; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids
keywords: Statins; cholesterol; indirect comparison; meta-analysis; mixed treatment comparison; systematic review