Heart failure & cardiomyopathies

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

Eur Heart J Cardiovasc PharmacotherPublished observational cohort study

Main finding · All-cause mortalityResult — go to the resultHazard ratio 0.78 95% CI 0.62–0.98

Authors' conclusion

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.

Study context

Population
Adults with a first heart failure (HF) diagnosis in Stockholm County (2005–2019) prescribed either spironolactone or eplerenone within 6 monthsinitiated a mineralocorticoid receptor antagonist, of 75,565 patients with new-onset HF
Participants
12,046 adults
Exposure
Eplerenone vs. spironolactone
  • Eplerenonen = 1,007
  • Spironolactonen = 11,039reference
Outcome
All-cause mortality
Methodological detailsregistry-based new-user cohort, linked Swedish registries with individual-level laboratory results, intention-to-treat principle, multivariable Cox regression, sensitivity analyses including propensity score matching
  • Registry-based new-user cohort
  • Linked Swedish registries with individual-level laboratory results
  • Intention-to-treat principle
  • Multivariable Cox regression
  • Sensitivity analyses including propensity score matching

Main finding

As reported in the abstract

Hazard ratio

0.78

95% CI 0.62–0.98

Eplerenonevs spironolactone
hazard ratio 0.78 (95% CI 0.62–0.98)

Observational data: associations, not effects.

Further findings

OutcomeEstimate
More than 50% decline in eGFRhazard ratio 0.69 (95% CI 0.54–0.88)
Sustained eGFR below 30 mL/min/1.73 m²hazard ratio 0.69 (95% CI 0.49–0.95)
Composite kidney outcomehazard ratio 0.71 (95% CI 0.56–0.90)
HF hospitalizationEplerenonevs spironolactonecause-specific hazard ratio 1.29 (95% CI 1.11–1.51)
HF hospitalizationEplerenonevs spironolactoneAttenuated when death was treated as a competing riskhazard ratio, death as competing risk 0.99 (95% CI 0.87–1.12)

Sensitivity analyses

Findings were robust across sensitivity analyses

Safety

OutcomeHazard ratio (95% CI)
Hyperkalaemia of 5.5 mmol/L or above0.76 (0.60–0.96)

Original publication

Eplerenone vs. spironolactone in heart failure: long-term cardiorenal and mortality outcomes in a registry-based cohort. Eur Heart J Cardiovasc Pharmacother. Published 10 September 2026. doi:10.1093/ehjcvp/pvag064

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