Elsevier

American Heart Journal

Volume 151, Issue 2, February 2006, Pages 273-281
American Heart Journal

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

https://doi.org/10.1016/j.ahj.2005.04.003Get rights and content

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 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.

Section snippets

Study selection

We identified RCTs of pravastatin, simvastatin, and atorvastatin through a systematic literature search in the MEDLINE and the Cochrane Controlled Trials Register databases (Update Software Ltd, Oxford, UK, 2004) between 1980 and 2004 for English-language studies using the keywords atorvastatin, simvastatin, and pravastatin in combination with any of the following words: cholesterol, prevention, cardiovascular disease, myocardial infarction, coronary heart disease, ischemic heart disease, stroke

Results

The search resulted in 745 studies. Trials were excluded because they were ongoing trials (n = 56) or did not study CVD or death as the outcome (n = 678), or had <1 year follow-up (n = 1, MIRACL43). No trial that studied clinical outcomes (CVD or death) was excluded because of having <1000 subjects. Eight placebo-controlled RCTs met the inclusion criteria. These included 4 pravastatin trials (WOSCOPS1, CARE2, LIPID3, PROSPER5; total n = 25 572), 2 simvastatin trials (4S7, HPS8; total n = 24 980),

Discussion

Using the method of adjusted indirect comparison, we compared 3 major statins based on published large placebo-controlled RCTs. Our results revealed no statistically significant difference in the 3 statins used at their standard dosages for long-term cardiovascular prevention. Although there appears a trend that atorvastatin and simvastatin have a greater reduction in the major cardiac events.

The benefit of statins as a group is unquestionable, yet comparative data regarding the relative

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    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.

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