What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure (n=12046). Intervention: Eplerenone vs. Spironolactone. Primary outcome: All-cause mortality (HR 0.78, 95% CI 0.62-0.98).

What question did this study set out to answer?

Compare long-term cardiorenal and mortality outcomes between eplerenone and spironolactone in a registry-based cohort of patients with new-onset heart failure.

August 16, 2026European Heart Journal - Cardiovascular PharmacotherapyOpen Access

Eplerenone linked to ~22% lower all-cause mortality vs spironolactone in new-onset HF.

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Why the study?

Eplerenone and spironolactone differ pharmacologically, but whether this translates into meaningful differences in clinical outcomes in heart failure remains uncertain.

Does eplerenone improve mortality and cardiorenal outcomes compared to spironolactone in adults with new-onset heart failure?

Population

12 046 adults with new-onset HF initiating an MRA in Stockholm County

Comparison

Eplerenone vs spironolactone

Design

Registry-based observational new-user cohort study

Key result

Eplerenone was associated with lower all-cause mortality compared with spironolactone in adults with new-onset heart failure (HR 0.78; 95% CI 0.62-0.98).

Authors

KWKarl Wärnberg CHCarl Haggård KBKarin Bergen

Discussion

Member takes

Overview

May support preferring eplerenone over spironolactone in new-onset HF; leaves open confirmation in randomized trials.

Key Points

Compare long-term cardiorenal and mortality outcomes between eplerenone and spironolactone in a registry-based cohort of patients with new-onset heart failure.
Observational cohort study linking Swedish registries and serial laboratory data for adults diagnosed with heart failure in Stockholm County (2005–2019) who initiated spironolactone (N=11 039) or eplerenone (N=1007) within 6 months.
Evaluated outcomes on an intention-to-treat basis using multivariable Cox regression and propensity score matching, with heart failure hospitalization analyzed cause-specifically and accounting for death as a competing risk.
Eplerenone was associated with significantly reduced all-cause mortality (HR 0.78, 95% CI 0.62–0.98) and a reduced risk of hyperkalaemia ≥5.5 mmol/L (HR 0.76, 95% CI 0.60–0.96).
Renal outcomes favored eplerenone, including lower hazards for >50% eGFR decline (HR 0.69, 95% CI 0.54–0.88), sustained eGFR <30 mL/min/1.73 m² (HR 0.69, 95% CI 0.49–0.95), and the composite kidney outcome (HR 0.71, 95% CI 0.56–0.90).
Cause-specific hazard for heart failure hospitalization was higher with eplerenone (HR 1.29, 95% CI 1.11–1.51), but attenuated when accounting for death as a competing risk (HR 0.99, 95% CI 0.87–1.12).

Study Design

Type

Cohort (n=12,046)

Structured PICO

Does eplerenone improve mortality and cardiorenal outcomes compared to spironolactone in adults with new-onset heart failure?

Population

12,046 adults with a first heart failure diagnosis who initiated either spironolactone or eplerenone within 6 months.

Exposure

Eplerenone (n=1,007)

Comparator

Spironolactone (n=11,039)

Outcome

All-cause mortality, heart failure hospitalization, kidney function decline, and hyperkalaemiahard clinical

Main Result

Hazard Ratio: 0.78 (95% CI 0.62–0.98)

In a registry-based cohort of new-onset heart failure patients, eplerenone was associated with lower all-cause mortality, less kidney function decline, and a lower risk of hyperkalemia compared to spironolactone.

Limitations

Observational design; findings warrant confirmation in randomized comparisons.
Observational design requiring confirmation in randomized comparisons

Cite This Study

Wärnberg et al. (2026) conducted a cohort in Heart failure (n=12,046). Eplerenone vs. Spironolactone was evaluated on All-cause mortality (HR 0.78, 95% CI 0.62-0.98). Eplerenone was associated with lower all-cause mortality compared with spironolactone in adults with new-onset heart failure (HR 0.78; 95% CI 0.62-0.98).

synapsesocial.com/papers/6aa44ac634a74eb94ec805bc https://doi.org/10.1093/ehjcvp/pvag064

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August 16, 2026European Heart Journal - Cardiovascular PharmacotherapyOpen Access

Eplerenone linked to ~22% lower all-cause mortality vs spironolactone in new-onset HF.

View Full Paper

Ask AI

Bookmark

Why the study?

Eplerenone and spironolactone differ pharmacologically, but whether this translates into meaningful differences in clinical outcomes in heart failure remains uncertain.

Does eplerenone improve mortality and cardiorenal outcomes compared to spironolactone in adults with new-onset heart failure?

Population

12 046 adults with new-onset HF initiating an MRA in Stockholm County

Comparison

Eplerenone vs spironolactone

Design

Registry-based observational new-user cohort study

Key result

Eplerenone was associated with lower all-cause mortality compared with spironolactone in adults with new-onset heart failure (HR 0.78; 95% CI 0.62-0.98).

Authors

KWKarl Wärnberg CHCarl Haggård KBKarin Bergen

Discussion

Member takes

Overview

May support preferring eplerenone over spironolactone in new-onset HF; leaves open confirmation in randomized trials.

Key Points

Compare long-term cardiorenal and mortality outcomes between eplerenone and spironolactone in a registry-based cohort of patients with new-onset heart failure.
Observational cohort study linking Swedish registries and serial laboratory data for adults diagnosed with heart failure in Stockholm County (2005–2019) who initiated spironolactone (N=11 039) or eplerenone (N=1007) within 6 months.
Evaluated outcomes on an intention-to-treat basis using multivariable Cox regression and propensity score matching, with heart failure hospitalization analyzed cause-specifically and accounting for death as a competing risk.
Eplerenone was associated with significantly reduced all-cause mortality (HR 0.78, 95% CI 0.62–0.98) and a reduced risk of hyperkalaemia ≥5.5 mmol/L (HR 0.76, 95% CI 0.60–0.96).
Renal outcomes favored eplerenone, including lower hazards for >50% eGFR decline (HR 0.69, 95% CI 0.54–0.88), sustained eGFR <30 mL/min/1.73 m² (HR 0.69, 95% CI 0.49–0.95), and the composite kidney outcome (HR 0.71, 95% CI 0.56–0.90).
Cause-specific hazard for heart failure hospitalization was higher with eplerenone (HR 1.29, 95% CI 1.11–1.51), but attenuated when accounting for death as a competing risk (HR 0.99, 95% CI 0.87–1.12).

Study Design

Type

Cohort (n=12,046)

Structured PICO

Does eplerenone improve mortality and cardiorenal outcomes compared to spironolactone in adults with new-onset heart failure?

Population

12,046 adults with a first heart failure diagnosis who initiated either spironolactone or eplerenone within 6 months.

Exposure

Eplerenone (n=1,007)

Comparator

Spironolactone (n=11,039)

Outcome

All-cause mortality, heart failure hospitalization, kidney function decline, and hyperkalaemiahard clinical

Main Result

Hazard Ratio: 0.78 (95% CI 0.62–0.98)

Limitations

Observational design; findings warrant confirmation in randomized comparisons.
Observational design requiring confirmation in randomized comparisons

Cite This Study

synapsesocial.com/papers/6aa44ac634a74eb94ec805bc https://doi.org/10.1093/ehjcvp/pvag064

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

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