Current perspectives on mineralocorticoid receptor antagonists in the treatment of heart failure across the entire spectrum of ejection fraction

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.