Finerenone Outperforms Spironolactone, Eplerenone in HFpEF, HFmrEF Renal Outcomes

A new study comparing 3 mineralocorticoid receptor antagonists (MRAs) across the heart failure (HF) spectrum has demonstrated finerenone’s comparative efficacy in HF with preserved ejection fraction (HFpEF) and mildly reduced ejection fraction (HFmrEF).1

These data were presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026 in Phoenix, Arizona, by Hareem Saleem, MBBS, an internal medicine resident at Memorial Healthcare System Pembroke. The study was undertaken in response to the limited and inconsistent evidence of steroidal agents in HFpEF and HFmrEF.1,2

“Finerenone, a novel nonsteroidal MRA, has recently demonstrated significant reduction in heart failure events and cardiovascular death in patients with HFmrEF and HFpEF, addressing a critical therapeutic gap,” Saleem and colleagues wrote. “We performed a network meta-analysis to compare the efficacy and safety of finerenone with steroidal MRAs.”1

Saleem and colleagues conducted a PRISMA-guided network meta-analysis, identifying 1066 individual records. The team selected spironolactone and eplerenone as their comparators to finerenone. A total of 6 comparative studies were ultimately included after screening and eligibility assessment, and data extraction and quality appraisal were independently conducted by 2 reviewers. R software was then used to perform the meta-analysis and generate pooled and comparative effect estimates.1

Ultimately, the network meta-analysis scanned 3 randomized trials, encompassing 7 treatment arms and 17 pairwise comparisons. Saleem and colleagues saw no significant differences between finerenone and eplerenone for acute kidney injury (AKI) in random-effects models. However, lower doses of finerenone, namely 7.5-15 mg and 10-20 mg, showed a trend toward reduced AKI risk versus eplerenone (risk ratio [RR], 0.69 and 0.66, respectively). Spironolactone was associated with a greater risk of AKI compared to eplerenone (RR, 1.34) without statistical significance.1

Finerenone 15-20 mg was associated with a greater AKI risk reduction than spironolactone in common-effects analysis (RR, 0.83; 95% CI, 0.69-0.98). However, this was not maintained in random-effects models. The team recorded moderate heterogeneity with no significant inconsistency between direct and indirect estimates.1

Ranking analysis favored low-to-moderate doses of finerenone regarding renal safety – in contrast, spironolactone ranked the lowest of the 3 treatments. Similar trends were recorded for renal worsening and hyperkalemia outcomes, with finerenone demonstrating a superior safety profile compared with spironolactone and non-significant differences versus eplerenone.1

Ultimately, the team concluded that finerenone displays substantially greater efficacy in patients with HFpEF and HFmrEF compared to other MRAs, particularly in regard to renal outcomes. However, Saleem and colleagues also noted the need for more direct clinical comparison to validate these results and determine the ideal MRA for each presentation.1

“Finerenone represents an important advancement in the management of HFpEF and HFmrEF, demonstrating improved heart failure outcomes compared with traditional steroidal MRAs, with a favorable safety profile,” Saleem and colleagues wrote. “These findings support its emerging role within guideline-directed therapy and underscore the need for head-to-head trials to define optimal MRA selection across the HF spectrum.”1

References

1. Saleem H, Hafeez A, Raja A, et al. Comparative Effectiveness of Finerenone, Spironolactone, and Eplerenone Across Heart Failure Spectrum: A Network Meta-analysis. Abstract presented at the Heart Failure Society of America (HFSA) Annual Scientific Meeting 2026, Phoenix, AZ. October 9-12, 2026.

2. Habib E, Ibrahim R, Pham HN, Abdelnabi M, Kanaan C, Eldeib A, Augusto SN Jr, Ayoub C, Tang WHW, Arsanjani R. Finerenone Versus Spironolactone for Heart Failure with Preserved Ejection Fraction. Cardiovasc Drugs Ther. 2026 Aug;40(4):1419-1422. doi: 10.1007/s10557-025-07822-x.