Key result
MRAs improve heart failure outcomes across ejection fractions, led by ~30% lower mortality with spironolactone in HFrEF.
Why the study?
Steroidal and nonsteroidal MRAs differ in selectivity and safety, prompting a synthesis of the available evidence on their use in HF across the entire LVEF spectrum.
Do mineralocorticoid receptor antagonists (spironolactone, eplerenone, finerenone) reduce mortality and heart failure hospitalizations across the entire spectrum of left ventricular ejection fraction?
Do mineralocorticoid receptor antagonists (spironolactone, eplerenone, finerenone) reduce mortality and heart failure hospitalizations across the entire spectrum of left ventricular ejection fraction?
This narrative review highlights that while steroidal MRAs are foundational in HFrEF, the nonsteroidal MRA finerenone effectively expands treatment options to patients with HFmrEF and HFpEF by reducing heart failure worsening with a favorable safety profile.
Supports MRA use in HFrEF and finerenone for LVEF ≥40%; extends evidence across EF spectrum but needs direct comparisons.
Heart failure (HF) is a clinical syndrome with high prevalence and mortality, classified according to left ventricular ejection fraction (LVEF) as HF with reduced (HFrEF), mildly reduced (HFmrEF), or preserved (HFpEF) ejection fraction.Activation of the renin-angiotensin-aldosterone system promotes inflammation, fibrosis, and myocardial remodeling that can be mitigated using mineralocorticoid receptor antagonists (MRAs).These are divided into steroidal (spironolactone and eplerenone) and nonsteroidal (finerenone) medications, with different selectivity and safety.This article describes the available evidence on the use of MRAs across the entire LVEF spectrum.A narrative review was performed using a search in PubMed, Embase, Scopus, and the Cochrane Library between 1999 and 2025.In HFrEF, steroidal MRAs have demonstrated tangible benefits.The RALES study showed a 30% reduction in total mortality with spironolactone, while EPHESUS and EMPHASIS-HF confirmed that eplerenone reduces mortality and hospitalizations for HF.However, these drugs increase the risk of hyperkalemia, especially in patients with chronic kidney disease.In HFmrEF and HFpEF, the evidence for spironolactone has been mixed; although TOPCAT did not significantly reduce the primary outcome, it did reduce hospitalizations for HF.FINEARTS-HF indicated that finerenone significantly reduces HF worsening in patients with LVEF ≥ 40%.Mineralocorticoid receptor antagonists continue to be essential for HF, and finerenone expands treatment options for HFmrEF and HFpEF, with clinical efficacy and a favorable safety profile.
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Saldarriaga et al. (2026) conducted a review in Heart failure across the entire spectrum of left ventricular ejection fraction (HFrEF, HFmrEF, and HFpEF). Mineralocorticoid receptor antagonists (spironolactone, eplerenone, finerenone) was evaluated on Total mortality and heart failure hospitalizations/worsening. Mineralocorticoid receptor antagonists improve heart failure outcomes, with spironolactone reducing mortality by 30% in HFrEF and finerenone reducing HF worsening in LVEF ≥40%.
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