Matched HF Cohort Links Finerenone to Lower Death or Exacerbation Risk Than Spironolactone

Finerenone initiation was associated with a lower 12-month risk of all-cause mortality or heart failure (HF) exacerbation than spironolactone initiation in adults with HF and a left ventricular ejection fraction of 40% or greater, according to a retrospective cohort study conducted at Taipei Medical University Hospital in Taiwan and published in ESC Heart Failure.

The investigators noted that no randomized trial has directly compared finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist (MRA), with spironolactone, a steroidal MRA, in patients with HF with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

The active-comparator, new-user study used electronic health record data from the TriNetX network between July 9, 2021, and March 31, 2025. After 1:1 propensity score matching, 1,417 patients were included in each group. The primary composite outcome occurred in 32.3% of finerenone users and 41.7% of spironolactone users (adjusted hazard ratio [aHR], 0.72; 95% CI, 0.64-0.82). Finerenone was also associated with lower risks of all-cause mortality (aHR, 0.67), HF exacerbation (aHR, 0.73), and all-cause hospitalization (aHR, 0.83), but not acute myocardial infarction (aHR, 0.82; 95% CI, 0.68-1.00).

Hyperkalemia occurred less often with finerenone (17.9% vs 22.8%; risk ratio, 0.79; 95% CI, 0.68-0.91). Acute kidney injury occurred in 34.6% and 38.2% of patients, respectively (risk ratio, 0.90; 95% CI, 0.82-0.998), a difference the authors described as borderline. In subgroup analyses, which the authors characterized as descriptive, associations with the primary outcome did not reach significance in patients with HFmrEF or in those without type 2 diabetes mellitus (T2DM).

The authors noted that during the study period, finerenone was prescribed almost exclusively to ambulatory patients with T2DM and chronic kidney disease, and that unmeasured factors such as frailty were the most likely explanation for the size of the mortality association. They stated that causal inference cannot be established and that the findings apply to a finerenone-eligible, predominantly cardiorenal population. The investigators concluded that the results should be considered hypothesis-generating and require confirmation in randomized head-to-head trials.

Source: Ha PTK, Chao CJ, Hung CL, et al. Finerenone versus spironolactone in heart failure with mildly reduced or preserved ejection fraction: a real-world study. ESC Heart Fail. Published online September 30, 2026. doi:10.1093/eschf/xvag246