Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants

Am Heart J. 2019 Apr:210:18-28. doi: 10.1016/j.ahj.2018.12.007. Epub 2019 Jan 10.

Abstract

The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations.

Methods: We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes.

Results: In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile.

Conclusions: All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.

Publication types

  • Comparative Study
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Atorvastatin / adverse effects
  • Atorvastatin / therapeutic use
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Cause of Death
  • Chemical and Drug Induced Liver Injury / etiology
  • Double-Blind Method
  • Fluvastatin / adverse effects
  • Fluvastatin / therapeutic use
  • Headache / chemically induced
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Kidney Diseases / chemically induced
  • Lovastatin / adverse effects
  • Lovastatin / therapeutic use
  • Middle Aged
  • Muscular Diseases / chemically induced
  • Nausea / chemically induced
  • Neoplasms / chemically induced
  • Network Meta-Analysis*
  • Placebos / therapeutic use
  • Pravastatin / adverse effects
  • Pravastatin / therapeutic use
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Risk Assessment
  • Rosuvastatin Calcium / adverse effects
  • Rosuvastatin Calcium / therapeutic use
  • Simvastatin / adverse effects
  • Simvastatin / therapeutic use
  • Withholding Treatment

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Placebos
  • Fluvastatin
  • Rosuvastatin Calcium
  • Lovastatin
  • Atorvastatin
  • Simvastatin
  • Pravastatin