Finerenone versus spironolactone in heart failure with mildly reduced or preserved ejection fraction: a real-world study.

AIMS: Finerenone has shown benefit in chronic kidney disease, type 2 diabetes, and heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), but head-to-head data against spironolactone are limited. We compared 12-month effectiveness and safety after finerenone versus spironolactone initiation in heart failure with left ventricular ejection fraction ≥40%. METHODS AND RESULTS: We conducted a retrospective active-comparator, new-user cohort study using the TriNetX Network from 9 July 2021 to 31 March 2025. Adults of both sexes with HFmrEF/HFpEF initiating finerenone or spironolactone were matched 1:1 by propensity score. The primary outcome was all-cause mortality or heart failure exacerbation. Secondary outcomes included all-cause mortality, heart failure exacerbation, all-cause hospitalisation, and acute myocardial infarction; safety outcomes were hyperkalaemia and acute kidney injury. After matching, 1417 patients were included in each group. Finerenone initiation was associated with lower risk of the primary outcome (32.3% vs. 41.7%; adjusted hazard ratio [aHR] 0.72, 95% confidence interval [CI] 0.64-0.82; P < 0.001). Lower risks were also observed for all-cause mortality (aHR 0.67, 95% CI 0.51-0.87), heart failure exacerbation (aHR 0.73, 95% CI 0.64-0.83), and all-cause hospitalisation (aHR 0.83, 95% CI 0.76-0.91), but not acute myocardial infarction. Hyperkalaemia was less frequent with finerenone (17.9% vs. 22.8%; risk ratio 0.79, 95% CI 0.68-0.91); acute kidney injury showed only a borderline difference. CONCLUSIONS: Finerenone initiation was associated with lower 12-month clinical event and hyperkalaemia risks than spironolactone initiation. These observational associations should be considered hypothesis-generating and require confirmation in randomised head-to-head trials.