Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170 255 patients from 76 randomized trials

BACKGROUND: Statins represent the largest selling class of cardiovascular drug in the world. Previous randomized trials (RCTs) have demonstrated important clinical benefits with statin therapy. AIM: We combined evidence from all RCTs comparing a statin with placebo or usual care among patients with and without prior coronary heart disease (CHD) to determine clinical outcomes. DESIGN: We searched independently, in duplicate, 12 electronic databases (from inception to August 2010), including full text journal content databases, to identify all statin versus inert control RCTs. We included RCTs of any statin versus any non-drug control in any populations. We abstracted data in duplicate on reported major clinical events and adverse events. We performed a random-effects meta-analysis and meta-regression. We performed a mixed treatment comparison using Bayesian methods. RESULTS: We included a total of 76 RCTs involving 170,255 participants. There were a total of 14,878 deaths. Statin therapy reduced all-cause mortality, Relative Risk (RR) 0.90 95% confidence interval (CI) 0.86-0.94, P ≤ 0.0001, I(2)=17%; cardiovascular disease (CVD) mortality (RR 0.80, 95% CI 0.74-0.87, P<0.0001, I(2)=27%); fatal myocardial infarction (MI) (RR 0.82, 95% CI 0.75-0.91, P<0.0001, I(2)=21%); non-fatal MI (RR 0.74, 95% CI 0.67-0.81, P ≤ 0.001, I(2)=45%); revascularization (RR 0.76, 95% CI 0.70-0.81, P ≤ 0.0001); and a composite of fatal and non-fatal strokes (0.86, 95% CI 0.78-0.95, P=0.004, I(2)=41%). Adverse events were generally mild, but 17 RCTs reported on increased risk of development of incident diabetes Odds Ratio (OR) 1.09; 95% CI 1.02-1.17, P=0.001, I(2)=11%. Studies did not yield important differences across populations. We did not find any differing treatment effects between statins. DISCUSSION: Statin therapies offer clear benefits across broad populations. As generic formulations become more available efforts to expand access should be a priority.