This study aimed to evaluate the effectiveness of 3-hydroxy-3-methyl-glutaryl-CoA
reductase inhibitors (statins) in primary prevention of cardiovascular events.
The role of statins is well established for secondary prevention of cardiovascular
disease (CVD) clinical events and mortality. Little is known of their role in primary
cardiovascular event prevention.
We conducted comprehensive searches of 10 electronic databases from inception to May
2008. We contacted study investigators and maintained a comprehensive bibliography
of statin studies. We included randomized trials of at least 12-month duration in
predominantly primary prevention populations. Two reviewers independently extracted
data in duplicate. We performed random-effects meta-analysis and meta-regression,
calculated optimal information size, and conducted a mixed-treatment comparison analysis.
We included 20 randomized clinical trials. We pooled 19 trials (n = 63,899) for all-cause
mortality and found a relative risk (RR) of 0.93 (95% confidence interval [CI]: 0.87
to 0.99, p = 0.03 [I(2) = 5%, 95% CI: 0% to 51%]). Eighteen trials (n = 59,469) assessed
cardiovascular deaths (RR: 0.89, 95% CI: 0.81 to 0.98, p = 0.01 [I(2) = 0%, 95% CI:
0% to 41%]). Seventeen trials (n = 53,371) found an RR of 0.85 (95% CI: 0.77 to 0.95,
p = 0.004 [I(2) = 61%, 95% CI: 38% to 77%]) for major cardiovascular events, and 17
trials (n = 52,976) assessed myocardial infarctions (RR: 0.77, 95% CI: 0.63 to 0.95,
p = 0.01 [I(2) = 59%, 95% CI: 24% to 74%]). Incidence of cancer was not elevated in
10 trials (n = 45,469) (RR: 1.02, 95% CI: 0.94 to 1.11, p = 0.59 [I(2) = 0%, 95% CI:
0% to 46%]), nor was rhabdomyolysis (RR: 0.97, 95% CI: 0.25 to 3.83, p = 0.96 [I(2)
= 0%, 95% CI: 0% to 40%]). Our analysis included a sufficient sample to reliably answer
our primary outcome of CVD mortality.
Statins have a clear role in primary prevention of CVD mortality and major events.