Finerenone and the Role of Combination Therapy in HFmrEF/HFpEF

With an approval from the US Food and Drug Administration (FDA) for the management of heart failure with mildly reduced or preserved ejection fraction in hand and backed by the phase 3 FINEARTS-HF trial, finerenone (Kerendia) could soon become a pillar of therapy for this patient population alongside the SGLT2 inhibitor class.

In part 3 of this 4-part HCPLive RX Review, Stephen Greene, MD, Muthiah Vaduganathan, MD, MPH, and Andrew Sauer, MD, reflect on the prospect of combination therapy using finerenone. Vaduganathan offers an overview of the CONFIDENCE trial—a randomized study examining combination therapy with finerenone and empagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD).

CONFIDENCE enrolled 800 patients with type 2 diabetes and albuminuric CKD, randomized into three arms: finerenone alone, empagliflozin alone, and a combination of both. The primary endpoint was a reduction in urine albumin-to-creatinine ratio (UACR) over 180 days. Results indicated the reduction in the UACR with combination therapy was 29% greater than that with finerenone alone (least-squares mean ratio of the difference in the change from baseline, 0.71; 95% confidence interval [CI], 0.61 to 0.82; P <.001) and 32% greater than that with empagliflozin alone (least-squares mean ratio of the difference in the change from baseline, 0.68; 95% CI, 0.59 to 0.79; P <.001)

As Vaduganathan points out, the benefits of combination therapy emerged early in the trial, were sustained, and attenuated upon therapy withdrawal in a post-treatment observation period. This durability signal reinforced a key message: clinical benefit depends on consistent treatment adherence. Vaduganathan underlined these data indicate therapies for progressive cardiorenal conditions only work when taken continuously—emphasizing the need for ongoing patient engagement and persistence.

Before closing, Greene concluded that data from CONFIDENCE offer important lessons for heart failure care: initiating multiple, complementary therapies early rather than slowly sequencing over time may yield better outcomes and reduce the risk of preventable hospitalizations and deaths in patients with preserved ejection fraction and related conditions.

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