Aldosterone blockade and left ventricular dysfunction: a systematic review of randomized clinical trials

Context: Aldosterone blockade has been used to treat acute myocardialinfarction (MI) and chronic heart failure. Objective: The aim of this study is to summarize the evidence on the efficacyof spironolactone (SP), eplerenone (EP), or canrenoate (CAN)in patients with left ventricular dysfunction. Data sources: A search of multiple electronic databases until June 2008 wassupplemented by hand searches of reference lists of includedstudies and review articles, meeting abstracts, FDA reports,and contact with study authors and drug manufacturers. Study selection and data extraction: Studies were eligible for inclusion if they included patientswith left ventricular systolic or diastolic dysfunction, treatmentwith SP, EP, or CAN vs. control, and reported clinical outcomes.Nineteen randomized controlled trials (four in acute MI and15 in heart failure, n = 10 807 patients) were included—14of SP, three of EP, and three of CAN. Analysis was performedusing relative risks (RRs) with 95% confidence intervals (CIs)and a random effects model with statistical heterogeneity assessedby I². Data synthesis: Aldosterone blockade reduced all-cause mortality by 20% (RR0.80, 95% CI 0.74–0.87). All-cause mortality was reducedin both heart failure (RR = 0.75, 95% CI 0.67–0.84) andpost-MI (RR 0.85, 95% CI 0.76–0.95) patients. Only ninetrials reported hospitalizations, and the RR reduction was 23%(RR 0.77, 95% CI 0.68–0.87), although 98% of the outcomescame from two trials. Ejection fraction (EF) improved in theseven heart failure trials, which assessed this outcome (weightedmean difference 3.1%, 95% CI 1.6–4.5). Conclusion: We demonstrated a 20% reduction in all-cause mortality withthe use of aldosterone blockade in a clinically heterogeneousgroup of clinical trial participants with heart failure andpost-MI. In addition, we found a 3.1% improvement in EF. Furtherstudy in those with less severe symptoms or preserved systolicfunction is warranted.