Meta-Analysis of Randomized Controlled Trials of Statins Versus Placebo in Patients With Heart Failure

Although statins have been shown to improve outcomes in retrospective analyses of patients with heart failure (HF), recent randomized placebo-controlled trials have shown mixed results. The goal of this study was to systematically review randomized trials comparing statins to placebo for HF and compare the impact of different statins. CENTRAL, mRCT, and PubMed were searched for eligible studies that prospectively randomized patients with HF to statins or placebo. Primary end points were all-cause mortality, cardiovascular mortality, hospitalization for worsening HF, adverse drug events, and changes in left ventricular ejection fraction (LVEF). Pooling was performed with random effect methods with summary effect estimates (95% confidence intervals). Ten studies (10,192 patients) with follow-up from 3 to 47 months were included. Three trials randomized patients to rosuvastatin, 1 to simvastatin, and 6 to atorvastatin. Overall, statins did not affect all-cause or cardiovascular mortality but did significantly decrease hospitalization for worsening HF during follow-up (odds ratio [OR] 0.67, p = 0.008). Patients randomized to statins had a significant 4.2% increase in LVEF at follow-up (95% confidence interval 1.3 to 7.1, p = 0.004). Furthermore, post hoc analyses showed heterogeneity among different statins and demonstrated that randomization to atorvastatin significantly decreased all-cause mortality (OR 0.39, p = 0.004), decreased hospitalization for worsening HF (OR 0.30, p <0.000 01), and randomization to atorvastatin and simvastatin led to a significant improvement in LVEF, whereas these benefits were not observed in patients randomized to rosuvastatin. In conclusion, meta-analysis of randomized controlled trials demonstrated that statins are safe and improve LVEF and decrease hospitalization for worsening HF.