Comparative effectiveness and safety of eplerenone and spironolactone in patients with heart failure: a systematic review and meta-analysis

BMC Cardiovasc Disord. 2024 Sep 13;24(1):489. doi: 10.1186/s12872-024-04103-7.

Abstract

Background: Eplerenone and spironolactone, recognized as mineralocorticoid receptor antagonists (MRAs), have been reported to improve clinical prognosis among individuals diagnosed with heart failure (HF). However, the difference in the clinical effects between eplerenone and spironolactone in individuals with HF remains uncertain. We aimed to assess the impact of eplerenone compared to spironolactone on clinical outcomes within the HF population.

Methods: An extensive search was executed in several databases (PubMed, Web of Science, Scopus, Cochrane Library). All relevant studies evaluating eplerenone compared to spironolactone in patients with HF were included. Dichotomous data were pooled as Hazard ratio (HR) or Risk ratio (RR) with a 95% confidence interval (CI). Our main outcome was all-cause mortality. Secondary outcomes included death from cardiovascular causes, treatment withdrawal, and gynecomastia.

Results: Ten studies, comprising 21,930 HF individuals, were included in our investigation. Eplerenone showed a lower risk of all-cause mortality (HR = 0.78, 95%CI [0.64 to 0.94], P = 0.009) and cardiovascular mortality (HR = 0.54, 95%CI [0.39, 0.74], P = 0.0001) compared to spironolactone. Furthermore, eplerenone exhibited a reduced risk of treatment withdrawal (RR = 0.69, 95% CI [0.62, 0.78], P = 0.0001) and gynecomastia (RR = 0.07, 95% CI [0.02 to 0.31], P = 0.0001) than spironolactone.

Conclusion: Eplerenone revealed lower all-cause and cardiovascular mortality events in comparison to spironolactone. Moreover, eplerenone was associated with lower gynecomastia and treatment withdrawal events compared to spironolactone. Further well-designed randomized controlled trials are still warranted better to identify the clinical differences between eplerenone and spironolactone.

Trial registration: Protocol registration: https://doi.org/10.17605/OSF.IO/VNMGK.

Keywords: Eplerenone; Heart failure; MRA; Mineralocorticoid receptor antagonist; Spironolactone.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cause of Death
  • Eplerenone* / adverse effects
  • Eplerenone* / therapeutic use
  • Female
  • Gynecomastia* / chemically induced
  • Gynecomastia* / diagnosis
  • Gynecomastia* / drug therapy
  • Gynecomastia* / mortality
  • Heart Failure* / diagnosis
  • Heart Failure* / drug therapy
  • Heart Failure* / mortality
  • Heart Failure* / physiopathology
  • Humans
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists* / adverse effects
  • Mineralocorticoid Receptor Antagonists* / therapeutic use
  • Recovery of Function
  • Risk Assessment
  • Risk Factors
  • Spironolactone* / adverse effects
  • Spironolactone* / analogs & derivatives
  • Spironolactone* / therapeutic use
  • Time Factors
  • Treatment Outcome

Substances

  • Eplerenone
  • Mineralocorticoid Receptor Antagonists
  • Spironolactone