Eplerenone vs. spironolactone in heart failure: long-term cardiorenal and mortality outcomes in a registry-based cohort

Eplerenone and spironolactone differ in pharmacological profile, but whether this translates into meaningful differences in clinical outcomes in heart failure (HF) remains uncertain. We compared the two agents in a registry-based new-user cohort with serial laboratory data.

In this observational cohort study, adults with a first HF diagnosis in Stockholm County (2005–2019) who were prescribed either spironolactone or eplerenone within 6 months were identified from linked Swedish registries with individual-level laboratory results. Follow-up was analysed under an intention-to-treat principle. Outcomes included all-cause mortality, HF hospitalization, kidney function decline, and hyperkalaemia. The main analysis used multivariable Cox regression. Several sensitivity analyses were performed, including propensity score matching. Of 75 565 patients with new-onset HF, 12 046 initiated a mineralocorticoid receptor antagonist (11 039 spironolactone; 1007 eplerenone). Eplerenone was associated with lower all-cause mortality (hazard ratio 0.78, 95% confidence interval 0.62–0.98), a lower risk of more than 50% decline in estimated glomerular filtration rate (eGFR) (0.69, 0.54–0.88), sustained eGFR below 30 mL/min/1.73 m² (0.69, 0.49–0.95), a composite kidney outcome (0.71, 0.56–0.90), and hyperkalaemia of 5.5 mmol/L or above (0.76, 0.60–0.96). The cause-specific hazard for HF hospitalization was higher with eplerenone (1.29, 1.11–1.51) but attenuated to 0.99 (0.87–1.12) when death was treated as a competing risk. Findings were robust across sensitivity analyses.

Compared with spironolactone, eplerenone was associated with lower all-cause mortality and lower risks of kidney function decline and mild hyperkalaemia. These observational findings warrant confirmation in randomized comparisons.