Eplerenone vs. spironolactone in heart failure: a propensity score-matched analysis of 77 904 patients from a global federated network.

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.