Mineralocorticoid receptor antagonists in heart failure: Comparative Insights on Spironolactone and Finerenone across the Ejection Fraction Spectrum

This review critically examines the evolving roles of mineralocorticoid receptor antagonists (MRAs), specifically spironolactone and finerenone, across the heart failure (HF) spectrum, from reduced to preserved ejection fraction. Spironolactone, a steroidal MRA, has demonstrated robust mortality and hospitalization benefits in heart failure with reduced ejection fraction (HFrEF), as evidenced by landmark trials such as RALES and TOPCAT. However, its use is limited by endocrine side effects and hyperkalemia. In contrast, finerenone, a novel non-steroidal MRA, exhibits higher receptor selectivity, a favorable safety profile, and equal distribution to cardiac and renal tissues. Clinical evidence from FIDELIO-DKD, FIGARO-DKD, and FINEARTS-HF highlights its efficacy in reducing cardiovascular events and HF hospitalizations, particularly in patients with preserved ejection fraction and comorbid chronic kidney disease or diabetes. This review synthesizes mechanistic insights, pharmacologic distinctions, and clinical outcomes, underscoring finerenone’s role in addressing unmet needs in HFpEF and HFmrEF populations. Limitations of prior trials, such as regional inconsistencies and varying patient characteristics, are discussed, along with the safety concerns surrounding hyperkalemia and renal function decline. Despite the lack of head-to-head trials, finerenone appears to offer a viable alternative for patients intolerant to steroidal MRAs. The integration of MRAs into guideline-directed therapy remains pivotal, and ongoing research exploring combined regimens, such as with SGLT2 inhibitors, may further refine their clinical utility. Ultimately, MRAs remain a cornerstone of HF management, with finerenone expanding therapeutic opportunities across a broader range of patient profiles.