Finerenone Versus Spironolactone for Heart Failure with Preserved Ejection Fraction

Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure with preserved ejection fraction (HFpEF), yet comparative effectiveness between steroidal and nonsteroidal agents remains unknown. Our aim was to compare cardiovascular and safety outcomes associated with finerenone versus spironolactone among patients with HFpEF.

This retrospective cohort study used a global federated health research network to identify adults with new-onset HFpEF between January 1, 2021, and August 1, 2025. Propensity score matching (1:1) balanced baseline characteristics, and outcomes were assessed with Cox proportional hazards models. A total of 253 patients prescribed finerenone and 32,266 prescribed spironolactone were identified; after matching, 251 patients were retained in each cohort (mean age, 73 years; 47% female). The primary outcome was acute HF events. Secondary outcomes included all-cause hospitalizations, mortality, myocardial infarction, stroke, and a composite of major adverse cardiovascular events. Safety outcomes included acute kidney injury (AKI) and hyperkalemia.

Acute HF events occurred in 6.0% of patients receiving finerenone and 4.4% receiving spironolactone (HR 1.26, 95% CI 0.58-2.74). All-cause mortality was lower with finerenone (4.4% vs. 8.0%; HR 0.48, 95% CI 0.23-1.00). Other clinical and safety outcomes, including MACE (11.6% vs. 10.8%), AKI (10.4% vs. 8.0%), and hyperkalemia (5.8% vs. 6.2%), were similar between groups.

In this first direct comparison of MRAs in HFpEF, finerenone demonstrated broadly comparable effectiveness and safety to spironolactone. While these observations are hypothesis-generating, prospective studies are warranted to confirm these findings and inform therapeutic decision-making.