Nonsteroidal Versus Steroidal Mineralocorticoid Receptor Antagonists in Heart Failure: Real‐World Evidence From a Multicenter Cohort Study

Background Mineralocorticoid receptor antagonists (MRAs) reduce mortality and hospitalization in patients with heart failure (HF). Finerenone, a selective nonsteroidal MRA, has recently demonstrated clinical benefits in patients with HF. However, real‐world evidence comparing nonsteroidal and steroidal MRAs in HF is lacking. Methods We conducted a retrospective, propensity score–matched cohort study using the TriNetX database. Adult patients diagnosed with HF from January 2021 to February 2025 who initiated nonsteroidal or a steroidal MRA were included. The primary outcome was a composite of all‐cause mortality, all‐cause hospitalization, and worsening HF at 1 year. Secondary outcomes included each component individually and safety events. Subgroup and sensitivity analyses were performed, including Kaplan–Meier survival, E‐value estimation, and landmark analysis. Results After matching, 1619 patients were included in each group. The incidence of the primary composite outcome was significantly lower in the nonsteroidal MRAs group (hazard ratio [HR], 0.79 [95% CI, 0.70–0.90]; P <0.001). Nonsteroidal MRAs were also associated with lower risks of all‐cause mortality (HR, 0.49), hospitalization (HR, 0.80), and worsening HF (HR, 0.76). Subgroup analyses showed consistent benefit. No significant differences in safety outcomes were observed. Conclusions In this large real‐world cohort, nonsteroidal MRAs use was associated with improved 1‐year clinical outcomes compared with steroidal MRAs in patients with HF. These findings support the potential clinical utility of nonsteroidal MRAs across HF phenotypes and highlight the need for further randomized studies to validate these results.