Differentiating Finerenone from Steroidal MRAs in HFpEF

In the concluding segment of this HCPLive RX Review, Stephen Greene, MD, Andrew Sauer, MD, and Muthiah Vaduganathan, MD, MPH, explored the comparative roles of finerenone (Kerendia), a nonsteroidal mineralocorticoid receptor antagonist (nsMRA) and steroidal mineralocorticoid receptor antagonists (MRAs), such as spironolactone, in the management of heart failure with mildly reduced ejection or preserved fraction (HFmrEF/HFpEF).

Sauer opened the discussion by acknowledging the foundational role of steroidal MRAs in heart failure, noting the survival benefits shown in trials like RALES. However, he emphasized the evidence supporting finerenone in HFpEF, particularly from the FINEARTS-HF trial and earlier kidney disease-focused studies, marks a significant shift in the field. Finerenone demonstrated cardiovascular and kidney protection across a broad population with cardio-kidney-metabolic disease, which was not shown definitively with spironolactone in the same context.

Both Sauer and Vaduganathan highlighted the limitations of the TOPCAT trial, which informed existing but cautious guideline support for spironolactone in HFpEF. Sauer notes differences in study quality, regional variations, and underdosing within TOPCAT left many clinicians uncertain about the applicability of its results. In contrast, the consistent benefits observed with finerenone, including a favorable safety profile, present a stronger case for use in current practice.

The panel also discussed key safety considerations. Highlighting finerenone showed a lower incidence of hypokalemia in clinical trials and a potentially more favorable risk-benefit balance compared to spironolactone, particularly in patients on diuretics or with CKD.

Panelists:

Stephen Greene, MD, is an advanced heart failure specialist and an associate professor in the Division of Cardiology at Duke Clinical Research Institute. Greene serves as moderator for this discussion.

Muthiah Vaduganathan, MD, MPH, is a cardiologist and the codirector of the Center for Cardiometabolic Implementation Science at Brigham and Women's Hospital. Vaduganathan also served as an investigator on the pivotal FINEARTS-HF trial.

Andrew Sauer, MD, is a cardiologist and the codirector of Cardiovascular Research as well as the executive director of the Cardiometabolic Center Alliance at Saint Luke's Health System.

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Relevant disclosures for Greene include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Relevant disclosures for Vaduganathan include Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, Lexicon, and others. Relevant disclosures for Sauer include Boston Scientific, Medtronic, Abbott, Impulse Dynamics, Amgen Inc., Biotronik, General Prognostics, Acorai, Bayer Healthcare Pharmaceuticals, CSL Vifor, and others.

References:

1. Bayer. U.S. FDA Approves KERENDIA® (finerenone) to Treat Patients With Heart Failure With Left Ventricular Ejection Fraction ≥40% Following Priority Review. Bayer. Published July 14, 2025. Accessed July 14, 2025. https://bayer2019tf.q4web.com/news/news-details/2025/U-S--FDA-Approves-KERENDIA-finerenone-to-Treat-Patients-With-Heart-Failure-With-Left-Ventricular-Ejection-Fraction-40-Following-Priority-Review/default.aspx

2. Solomon SD, John J.V. McMurray, Muthiah Vaduganathan, et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction. New England Journal of Medicine. 2024;391(16). doi: 10.1056/nejmoa2407107