European Journal of Heart Failure International Expert Position Paper Utilisation, Optimisation, and Clinical Benefits of Steroidal Mineralocorticoid Receptor Antagonists in Heart Failure with a Reduced Ejection Fraction

Abstract

Heart failure with reduced ejection fraction (HFrEF) imposes a significant clinical burden on patients and a major economic burden on healthcare systems. In HFrEF, mineralocorticoid receptor antagonists (MRAs) constitute a cornerstone of guideline-directed medical therapy (GDMT) reducing both mortality and hospitalisation. Their use in practice remains suboptimal, largely because of physicians' concerns about adverse events, particularly hyperkalaemia, which may deprive eligible patients of benefit. Only the steroidal MRAs spironolactone and eplerenone are approved for HFrEF, and this consensus document is restricted to these agents. We summarise contemporary evidence across multiple domains related to MRA therapy in HFrEF, including pharmacoepidemiology, the role of biomarkers in predicting outcomes and response to MRA, the pathological role of aldosterone and the pharmacology and clinical efficacy of steroidal MRAs. Practical, evidence-based guidance is provided on the prevention and management of hyperkalaemia, the timing of MRA initiation, and strategies to overcome barriers to MRA use. The positioning of MRAs in current guidelines is outlined to reinforce their central role in HFrEF. The process of consensus finding was started in April 2025 with a core group by online conference. We searched PubMed with the terms "MRA, eplerenone and heart failure with reduced ejection fraction". Articles published in English with no date restriction were considered. The final manuscript passed two rounds of final approval by all authors. As a result, this consensus statement advocates proactive, evidence-based approaches to optimise MRA use to improve outcomes. These recommendations aim to mitigate the persistent underuse of MRAs in clinical practice.