Eight placebo-controlled RCTs: 4 RCTs of pravastatin (n=25,572), 2 RCTs of simvastatin (n=24,980) and 2 RCTs of atorvastatin (n=13,143). Two additional RCTs that compared statins with usual care were included in the sensitivity analyses: one was of pravastatin (n=10,355) and the other was of atorvastatin (n=1,600).
All studies were double-blind and recruited consecutive patients. Attrition rates were reported as 3% or less. The average rate of noncompliance was reported as 15% or less.
All but one of the included studies (one of the usual care studies) reported a similar percentage change in total cholesterol and low-density cholesterol.
The L'Abbe plot showed that active treatment reduced major coronary events in all studies.
The only meta-analysis for which significant statistical heterogeneity was found was that of all-cause mortality among the studies of simvastatin (p=0.03).
For all included studies, statins significantly reduced fatal and nonfatal myocardial infarction (RR 0.75, 95% CI: 0.69, 0.81), fatal and nonfatal stroke (RR 0.81, 95% CI: 0.73, 0.89), all cardiovascular death (RR 0.82, 95% CI: 0.75, 0.89) and all-cause mortality (RR 0.85, 95% CI: 0.79, 0.92).
The meta-analysis of individual statins showed that all statins significantly reduced major coronary events compared with placebo: the RR was 0.78 (95% CI: 0.72, 0.83) for pravastatin versus placebo, 0.72 (95% CI: 0.67, 0.79) for simvastatin versus placebo, and 0.61 (95% CI: 0.48, 0.77) for atorvastatin versus placebo.
Adjusted indirect comparisons showed no statistically significant difference between statins for combined fatal coronary heart disease and nonfatal myocardial infarction: the RR was 0.93 (95% CI: 0.84, 1.03, p=0.18) for simvastatin versus pravastatin, 0.84 (95% CI: 0.66, 1.08, p=0.18) for atorvastatin versus simvastatin, and 0.79 (95% CI: 0.61, 1.02, p=0.06) for atorvastatin versus pravastatin. Similarly, there was no statistically significant difference between statins for fatal and nonfatal stroke, all cardiovascular death and all-cause mortality. After including the 2 RCTs with a usual-care control group, atorvastatin was found to reduce major coronary events compared with simvastatin (RR 0.79, 95% CI: 0.63, 0.99, p=0.04) and pravastatin (RR 0.71, 95% CI: 0.56, 0.90, p=0.004). There were no statistically significant differences between statins for other review outcomes.