Impact of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with heart failure and left-ventricular systolic dysfunction: an individual patient-level meta-analysis of three randomized-controlled trials

Rossello, X., Ariti, C., Pocock, S. J., Ferreira, J. P., Girerd, N., McMurray, J. J.V. , Van Veldhuisen, D. J., Pitt, B. and Zannad, F. (2019) Impact of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with heart failure and left-ventricular systolic dysfunction: an individual patient-level meta-analysis of three randomized-controlled trials. Clinical Research in Cardiology, 108, pp. 477-486. (doi: 10.1007/s00392-018-1378-0) (PMID:30264282)

Abstract

Background: Sudden 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. Methods: A 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. Results: Patients receiving MRAs were at lower risk of SCD compared with placebo-treated patients after a mean follow-up of 18 months (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 < 65 years 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 LVEF ≤ 35%. Conclusions: MRAs 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.

• Item Type: Articles
• Additional Information: Funding Dr Rossello received support from SEC-CNIC CARDIOJOVEN Program.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McMurray, Professor John
• Authors: Rossello, X., Ariti, C., Pocock, S. J., Ferreira, J. P., Girerd, N., McMurray, J. J.V., Van Veldhuisen, D. J., Pitt, B., and Zannad, F.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Clinical Research in Cardiology
• Publisher: Springer
• ISSN: 1861-0684
• ISSN (Online): 1861-0692
• Published Online: 27 September 2018