Are statins created equal? Evidence from randomized trials of pravastatin, simvastatin, and atorvastatin for cardiovascular disease prevention
Received 1 November 2004; accepted 1 April 2005.
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 = 25572), 2 simvastatin trials (n = 24980), and 2 atorvastatin trials (n = 13143). All trials had a similar degree of lipid reduction. Graphical and statistical assessments showed minimal heterogeneity in the trials' 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.
aDepartment of Epidemiology and Biostatistics, McGill University, Montréal, Quebec, Canada
bDivision of Clinical Epidemiology, Montréal General Hospital, Montréal, Quebec, Canada
Reprint requests: Louise Pilote MD, MPH, PhD, Division of Clinical Epidemiology, L10-421, Montreal General Hospital, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4.
Dr Zhou was supported by a research scholarship from the Natural Science and Engineering Research Council of Canada (NSERC) and a fellowship from the Canadian Cardiovascular Outcome Research Team (CCORT). Dr Rahme is a research scholar funded by the Arthritis Society. Dr Pilote is a research scholar of the Canadian Institute for Health Research (CIHR) and a William Dawson Professor at McGill University. None of the authors has financial interest or conflict with regard to the content discussed in this manuscript.
ABSTRACT