Key result
In adults with heart failure, eplerenone was associated with lower all-cause mortality than spironolactone at 36 months.
Why the study?
Whether eplerenone and spironolactone differ in effectiveness in heart failure remains uncertain due to an absence of head-to-head trials.
Does eplerenone reduce all-cause mortality, heart failure hospitalization, MACE, and CKD progression compared to spironolactone in adults with heart failure?
Cohort (n=77,904)
Yes
Does eplerenone reduce all-cause mortality, heart failure hospitalization, MACE, and CKD progression compared to spironolactone in adults with heart failure?
In a large propensity-matched cohort of heart failure patients, eplerenone was associated with lower mortality, MACE, and CKD progression compared to spironolactone overall and in HFrEF, though spironolactone was favored for MACE and HF hospitalization in HFpEF.
Answers are grounded in this paper and cite their sources.
May favor eplerenone over spironolactone for select HF outcomes; leaves open confirmation via randomized head-to-head trials.
Background Mineralocorticoid receptor antagonists (MRAs) reduce mortality in heart failure, yet whether eplerenone and spironolactone differ in effectiveness remains uncertain owing to the absence of head-to-head trials. Objective To compare all-cause mortality, heart failure hospitalization, major adverse cardiovascular events (MACE), and chronic kidney disease (CKD) progression between new users of eplerenone and spironolactone with heart failure. Methods Retrospective, new-user cohort study using the TriNetX Global Collaborative Network (171 healthcare organizations). Adults with heart failure receiving a first MRA prescription were matched 1 : 1 by propensity score. Prespecified subgroup analyses were performed in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Results After matching (38 952 pairs), all standardized mean differences (SMDs) were below 0.10 except serum potassium (SMD 0.18). At 36 months, eplerenone was associated with lower all-cause mortality [11.75 vs. 14.58%; hazard ratio 0.795, 95% confidence interval (CI) 0.765–0.827; P < 0.0001], heart failure hospitalization (hazard ratio 0.917, 95% CI 0.902–0.932), MACE (hazard ratio 0.900, 95% CI 0.886–0.915), and CKD progression (hazard ratio 0.803, 95% CI 0.745–0.867; all P < 0.0001). In HFrEF, eplerenone was associated with significantly lower rates across all outcomes. In HFpEF, mortality did not differ significantly (hazard ratio 0.946, 95% CI 0.876–1.021; P = 0.162), and spironolactone was associated with lower MACE (hazard ratio 1.135, 95% CI 1.087–1.184) and heart failure hospitalization (hazard ratio 1.144, 95% CI 1.108–1.181; both P < 0.0001). Conclusion In this large propensity score-matched cohort, eplerenone was associated with lower mortality, MACE, and CKD progression than spironolactone overall and in HFrEF. In HFpEF, spironolactone was favoured for MACE and heart failure hospitalization, with no significant difference in mortality. These hypothesis-generating findings support prospective head-to-head trials.
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Abomohsen et al. (2026) conducted a cohort in Heart failure (n=77,904). Eplerenone vs. Spironolactone was evaluated on All-cause mortality (HR 0.795, 95% CI 0.765-0.827, p=< 0.0001). In adults with heart failure, eplerenone was associated with lower all-cause mortality than spironolactone at 36 months.
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