Journal
CLINICAL RESEARCH IN CARDIOLOGY
Volume 108, Issue 5, Pages 477-486Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00392-018-1378-0
Keywords
Mineralocorticoid receptor antagonists; Sudden cardiac death; Heart failure; Left-ventricular dysfunction; Randomized clinical trials; Meta-analysis
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Funding
- SEC-CNIC CARDIO-JOVEN Program
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BackgroundSudden cardiac death (SCD) is an important cause of death in patients with left-ventricular systolic dysfunction (LVSD). Mineralocorticoid receptor antagonists (MRAs) may attenuate this risk. We aimed to assess the impact of MRAs on SCD in patients with LVSD.MethodsA fixed-effect meta-analysis at individual patient-level was performed using 11,032 patients recruited in three placebo-controlled randomized trials: Randomized Aldactone Evaluation Study (RALES), Eplerenone Post Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), and Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Treatment effect was determined using a Cox proportional hazards model stratified by study.ResultsPatients receiving MRAs were at lower risk of SCD compared with placebo-treated patients after a mean follow-up of 18months (HR 0.77, 95% CI 0.66-0.89). This effect was consistent across trials and did not change substantially after adjustment for 14 baseline co-variates. Moreover, the benefits of MRAs were consistent across study subgroups, except for a greater effect in those<65years old and those using beta-blockers. Using stratified analyses, we also found a consistent effect in relevant subsets of patient defined by heart failure cause, NYHA class or LVEF35%.ConclusionsMRAs reduce the risk for SCD by 23% in patients with heart failure and LVSD. In these patients, the use of MRAs, on top of other evidence-based medications, should be optimized. It might be useful to re-assess the benefit of implantable cardiac defibrillator (ICD) placement, as ICD treatment effect was evaluated in trials enrolling patients not receiving MRAs.
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