Finerenone Outperforms Spironolactone for Heart Failure Exacerbation in HFpEF, With Nihar Desai, MD, MPH

Finerenone use was associated with lower risks of heart failure exacerbation and all-cause mortality compared to spironolactone in patients with heart failure with preserved ejection fraction (HFpEF), based on a recent retrospective cohort study.1

Phase II studies have associated finerenone with reduced risks of hyperkalemia and deterioration in kidney function when compared with spironolactone and eplerenone in patients with chronic kidney disease (CKD). The recent FINEARTS-HF trial has also highlighted finerenone, investigating its efficacy in reducing heart failure hospitalization in patients with HFpEF. However, despite these trials, finerenone does not yet have an approved indication for HFpEF.2,3

“Spironolactone is a very important and highly effective therapy. The evidence to support its use in patients with reduced ejection fraction heart failure are unequivocal,” Nihar Desai, MD, MPH, associate professor of medicine at Yale School of Medicine and a contributing author in this study, told HCPLive in an exclusive interview. “However, the question arises regarding mid-range and preserved ejection fraction patients; spironolactone actually doesn’t have that as part of its indications. In contrast, using finerenone in those patients with an EF of ≥40% saw substantial clinical benefits.”

Desai and colleagues performed a retrospective observational cohort study via the TriNetX database, identifying all patients with a diagnosis of HFpEF. The team notes the potential limitations of TriNetX’s lack of additional datapoints, such as echocardiographic parameters and NYHA functional class, and the possible misclassification of patients within the HFpEF category.1

Patients were then further stratified based on finerenone or spironolactone use within 1 year of diagnosis. Concomitant spironolactone and/or finerenone use was excluded in both cohorts. The primary outcomes of the analysis were first or subsequent heart failure exacerbations, acute myocardial infarction, hypokalemia, ischemic stroke, all-cause mortality, sudden cardiac death, and hyperkalemia within a 1-year follow-up period. Acute myocardial infarction and ischemic stroke were included as secondary endpoints.1

Ultimately, the study included 254,417 patients with HFpEF; after propensity score matching, 491 patients were enrolled in each cohort, yielding a total of 982 participants. During the follow-up, the finerenone arm saw substantially lower statistically significant risk of heart failure exacerbation (55.2% vs 72.9%; HR, 0.63; 95% CI, 0.54-0.74; P <.001). Additionally, finerenone was associated with lower risks of all-cause mortality compared to spironolactone (4.1% vs 11.8%; HR, 0.38; 95% CI, 0.23-0.64; P <.001).1

Investigators also recorded a lower risk of hypokalemia in the finerenone cohort versus spironolactone (8.4% vs 15.1%; HR, 0.58; 95% CI, 0.4-0.85; P <.001). Despite not being statistically significant, similar trends were noted for hyperkalemia (13.8% vs 16.1%; HR, 0.96; 95% CI, 0.69-1.33). Sudden cardiac death was rare across both cohorts, affecting only 1 patient in the spironolactone arm and 10 in the finerenone arm.1

Desai and colleagues also performed subgroup analyses for patients with CKD and diabetes mellitus. Those with CKD saw substantially lower risk of heart failure exacerbation with finerenone versus spironolactone (59.4% vs 74.1%; HR, 0.63; 95% CI, 0.53-0.74; P <.001). The diabetes mellitus subgroup also saw lower heart failure exacerbation risk with finerenone (56.6% vs 74%; HR, 0.59; 95% CI, 0.5-0.69; P <.001).1

Despite the strength of these data, this study is solely hypothesis-generating. Desai and colleagues encourage further research, including head-to-head randomized controlled trials of finerenone versus spironolactone in HFpEF, to inform the debate over its safe and efficacious use in real-world settings.1

“If we’re going to follow the evidence and what the literature would tell us, finerenone would be a primary strategy in those patients with an EF ≥40% if finerenone is not available, or if there are other barriers that might restrict the use of finerenone,” Desai said. “Spironolactone is maybe an option B for a patient on the edges, but for most of our patients, we believe the data – finerenone seems to be the most effective MRA for those patients.”

Editor’s Note: Desai reports disclosures with Amgen, AstraZeneca, Novartis, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, and others.

References

1. Almas T, Shelig M, Al-Hindawi A, et al. Steroidal versus non-steroidal mineralocorticoid receptor antagonists in heart failure with preserved ejection fraction: A propensity-matched multi-network nationwide cohort study. European Heart Journal - Quality of Care and Clinical Outcomes. Published online January 30, 2026. doi:10.1093/ehjqcco/qcag014

2. Pitt B, Kober L, Ponikowski P, et al. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial. Eur Heart J. 2013;34(31):2453-2463. doi:10.1093/eurheartj/eht187

3. McCausland FR, Vaduganathan M, Claggett BL, et al. Finerenone and Kidney Outcomes in Patients With Heart Failure: The FINEARTS-HF Trial. J Am Coll Cardiol. 2025;85(2):159-168. doi:10.1016/j.jacc.2024.10.091