Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention

Background The relative efficacy of different statins for long-term cardiovascular prevention remains largely undetermined. Methods Using adjusted indirect comparison, we compared 3 statins (pravastatin, simvastatin, and atorvastatin) based on published randomized placebo-controlled trials for long-term cardiovascular prevention. A systematic literature search between 1980 and 2004 was conducted. Randomized placebo-controlled trials of the 3 statins, which studied cardiovascular diseases or death as the outcome, enrolled ≥1000 participants, and had ≥1-year follow-up, were included. Trials were grouped according to the statin under study. A pooled relative risk (RR) was derived from each set of trials using a random-effects model. Adjusted indirect comparisons using pooled RRs were made between statins with regard to prespecified clinical outcomes. Results Eight placebo-controlled trials met the inclusion criteria, including 4 pravastatin trials (n = 25 572), 2 simvastatin trials (n = 24 980), and 2 atorvastatin trials (n = 13 143). All trials had a similar degree of lipid reduction. Graphical and statistical assessments showed minimal heterogeneity in the trialsʹ effect sizes. Adjusted indirect comparisons did not reveal a statistically significant difference between statins in reducing fatal coronary heart disease and nonfatal myocardial infarctions (simvastatin vs pravastatin: RR 0.93 [95% CI 0.84-1.03]; atorvastatin vs simvastatin: RR 0.84 [95% CI 0.66-1.08]; atorvastatin vs pravastatin: RR 0.79 [95% CI 0.61-1.02]). We were unable to detect differences either in outcomes for fatal and nonfatal strokes, all cardiovascular deaths, and all-cause mortality. Conclusion Evidence from published statin randomized placebo-controlled trials suggests that pravastatin, simvastatin, and atorvastatin, when used at their standard dosages, show no statistically significant difference in their effect on long-term cardiovascular prevention.