Impact of Aldosterone Antagonists on Sudden Cardiac Death Prevention in Heart Failure and Post-Myocardial Infarction Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

PLoS One. 2016 Feb 18;11(2):e0145958. doi: 10.1371/journal.pone.0145958. eCollection 2016.

Abstract

Background and objectives: Sudden cardiac death (SCD) is a severe burden of modern medicine. Aldosterone antagonist is publicized as effective in reducing mortality in patients with heart failure (HF) or post myocardial infarction (MI). Our study aimed to assess the efficacy of AAs on mortality including SCD, hospitalization admission and several common adverse effects.

Methods: We searched Embase, PubMed, Web of Science, Cochrane library and clinicaltrial.gov for randomized controlled trials (RCTs) assigning AAs in patients with HF or post MI through May 2015. The comparator included standard medication or placebo, or both. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Event rates were compared using a random effects model. Prospective RCTs of AAs with durations of at least 8 weeks were selected if they included at least one of the following outcomes: SCD, all-cause/cardiovascular mortality, all-cause/cardiovascular hospitalization and common side effects (hyperkalemia, renal function degradation and gynecomastia).

Results: Data from 19,333 patients enrolled in 25 trials were included. In patients with HF, this treatment significantly reduced the risk of SCD by 19% (RR 0.81; 95% CI, 0.67-0.98; p = 0.03); all-cause mortality by 19% (RR 0.81; 95% CI, 0.74-0.88, p<0.00001) and cardiovascular death by 21% (RR 0.79; 95% CI, 0.70-0.89, p<0.00001). In patients with post-MI, the matching reduced risks were 20% (RR 0.80; 95% CI, 0.66-0.98; p = 0.03), 15% (RR 0.85; 95% CI, 0.76-0.95, p = 0.003) and 17% (RR 0.83; 95% CI, 0.74-0.94, p = 0.003), respectively. Concerning both subgroups, the relative risks respectively decreased by 19% (RR 0.81; 95% CI, 0.71-0.92; p = 0.002) for SCD, 18% (RR 0.82; 95% CI, 0.77-0.88, p < 0.0001) for all-cause mortality and 20% (RR 0.80; 95% CI, 0.74-0.87, p < 0.0001) for cardiovascular mortality in patients treated with AAs. As well, hospitalizations were significantly reduced, while common adverse effects were significantly increased.

Conclusion: Aldosterone antagonists appear to be effective in reducing SCD and other mortality events, compared with placebo or standard medication in patients with HF and/or after a MI.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Death, Sudden, Cardiac / pathology
  • Death, Sudden, Cardiac / prevention & control*
  • Gynecomastia / etiology
  • Gynecomastia / pathology
  • Heart Failure / mortality
  • Heart Failure / pathology
  • Heart Failure / prevention & control*
  • Humans
  • Hyperkalemia / etiology
  • Hyperkalemia / pathology
  • Mineralocorticoid Receptor Antagonists / administration & dosage*
  • Mineralocorticoid Receptor Antagonists / adverse effects
  • Myocardial Infarction / mortality
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Odds Ratio
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Renal Insufficiency / etiology
  • Renal Insufficiency / pathology
  • Survival Analysis
  • Treatment Outcome

Substances

  • Mineralocorticoid Receptor Antagonists

Grants and funding

The work has been done as a part of master internships of the three co-authors (HHL, CEK and MM). HHL is currently receiving a salary from Claude Bernard Lyon 1 University (scholarship of French Ministry of Higher Education & Research) for her three-year PhD at the UMR 5558 CNRS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.