Benefit of Finerenone in Heart Failure Not Modified by Atrial Fibrillation

A secondary analysis of the FINEARTS–HF randomized clinical trial found the efficacy of finerenone (KERENDIA) consistent, irrespective of atrial fibrillation (AF) status, in patients with heart failure (HF) and mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF).1

Previous trials suggest AF may attenuate treatment benefits in HFrEF, but finerenone, a nonsteroidal mineralocorticoid receptor agonist (nsMRA), showed consistent efficacy in HFmrEF and HFpEF, mirroring similar analyses for steroidal MRAs in HFrEF.2

“The key findings in this prespecified analysis of the FINEARTS-HF trial were that the effects of finerenone, compared with placebo, were consistent in patients with and without AF and by type of AF,” wrote the investigative team, led by John J. V. McMurray, MD, British Heart Foundation Cardiovascular Research Centre, University of Glasgow. “We also described the adjudicated incidence of clinically reported new-onset AF or AFL in patients with HFmrEF or HFpEF and outcomes related to this.”

Finerenone was initially approved by the US Food and Drug Administration (FDA) in 2021 to reduce the risk of sustained estimated glomerular filtration rate (eGFR), end-stage kidney disease, cardiovascular (CV) death, non-fatal myocardial infarction (MI), and hospitalization for HF in adults with CKD and T2D.3 The regulatory agency recently accepted finerenone’s supplemental New Drug Application (sNDA) targeting the treatment of adults with HF with a left ventricular ejection fraction (LVEF) of ≥40%.4

Acceptance of the sNDA was based on the FINEARTS-HF trial meeting its primary endpoint, with use of finerenone associated with a statistically significant 16% relative reduction in rate of primary outcome events compared with placebo therapy (rate ratio [RR], 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = .007).5

This subgroup analysis evaluated the efficacy and safety of finerenone according to baseline AF status in people with HFmrEF and HFpEF, with further evaluation of finerenone on the incidence of new-onset AF or atrial flutter. Participants in FINEARTS-HF, enrolled from 653 sites in 37 countries, were randomized to finerenone (titrated to 20 mg or 40 mg) or placebo between September 2020 and January 2023.1

A total of 5984 patients with known AF status at baseline were evaluated, of which 23.1% had paroxysmal AF and 31.5% had persistent or permanent AF. Patients had a mean age of 72.0 years and were 45.5% female. Those with both AF types were typically older and with worse HF status than those without AF (45.4%).

Upon analysis, patients with AF experienced a higher risk of the primary outcome, including paroxysmal AF (event rate per 100 person-years of follow-up, 20.3 [95% CI, 17.9–23.1]) and persistent or permanent AF (event rate, 19.8 [95% CI, 17.8-22.0]), compared with no AF (11.9 [95% CI, 10.7–13.3]). The rate ratios (RRs) were 1.62 (95% CI, 1.37–1.92) for paroxysmal AF and 1.66 (95% CI, 1.43-1.93) with persistent or permanent AF, respectively.

However, McMurray and colleagues noted AF at baseline was not associated with worse outcomes after adjustment for baseline prognostic variables, with similar results for paroxysmal and persistent or permanent AF.

Regarding the primary outcome, investigators found the overall benefit of finerenone (RR, 0.84 [95% CI, 0.74–0.95]) consistent in patients with no baseline AF (RR, 0.80 [95% CI, 0.65–0.98]), paroxysmal AF (RR, 0.83 [95% CI, 0.65–1.06]), and persistent or permanent AF (RR, 0.85 [95% CI, 0.69–1.05]) (P for interaction =.94).

Further analysis revealed new-onset AF or atrial flutter in 6.5% of patients during follow-up, which was linked to a higher risk of all subsequent outcomes (RR, 3.65 [95% CI, 2.57–5.18]; P <.001). Although those assigned to finerenone were less likely to experience new-onset AF or atrial flutter, compared with placebo, the between-treatment difference was not significant (subdistribution hazard ratio, 0.77 [95% CI, 0.57-1.04]; P = .09).

“While new-onset AF or atrial flutter was not frequently observed even in patients with established HFmrEF or HFpEF, it was associated with much worse subsequent outcomes,” McMurray and colleagues wrote.1 “Finerenone numerically appeared to reduce the incidence of new-onset AF or atrial flutter, although this effect was not statistically significant.”

References

1. Matsumoto S, Henderson AD, Jhund PS, et al. Finerenone and Atrial Fibrillation in Heart Failure: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial. JAMA Cardiol. Published online March 29, 2025. doi:10.1001/jamacardio.2025.0848

2. Jhund PS, Talebi A, Henderson AD, et al. Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis. Lancet. 2024;404(10458):1119-1131. doi:10.1016/S0140-6736(24)01733-1

3. Campbell P. Finerenone (Kerendia) approved for chronic kidney disease associated with type 2 diabetes. HCP Live. May 19, 2023. Accessed March 17, 2025. https://www.hcplive.com/view/finerenone-kerendia-approved-chronic-kidney-disease-associated-with-type-2-diabetes .

4. Iapoce C. FDA accepts Finerenone sNDA for heart failure, grants priority review. HCP Live. March 29, 2025. Accessed March 29, 2025. https://www.hcplive.com/view/fda-accepts-finerenone-snda-for-heart-failure-grants-priority-review.

5. Campbell P. Topline data prove Finerenone’s HFPEF benefit in Finearts-HF trial. HCP Live. August 5, 2024. Accessed March 29, 2025. https://www.hcplive.com/view/topline-data-prove-finerenone-s-hfpef-benefit-in-finerarts-hf-trial.