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Clin Res Cardiol. 2018 Sep 27. doi: 10.1007/s00392-018-1378-0. [Epub ahead of print]

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.

Author information

1
Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.
2
London School of Hygiene and Tropical Medicine, London, UK.
3
CIBER de enfermedades CardioVasculares (CIBERCV), Madrid, Spain.
4
School of Medicine, Cardiff University, Cardiff, UK.
5
Centre d'Investigation Clinique Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, Nancy, France.
6
BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, UK.
7
Department of Cardiology, University of Groningen, Groningen, The Netherlands.
8
Department of Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA.
9
Centre d'Investigation Clinique Plurithématique 1433, INSERM U1116, Université de Lorraine, CHRU de Nancy, Nancy, France. f.zannad@chu-nancy.fr.

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.

KEYWORDS:

Heart failure; Left-ventricular dysfunction; Meta-analysis; Mineralocorticoid receptor antagonists; Randomized clinical trials; Sudden cardiac death

PMID:
30264282
DOI:
10.1007/s00392-018-1378-0

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