What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure (n=77904). Intervention: Eplerenone vs. Spironolactone. Primary outcome: All-cause mortality (HR 0.795, 95% CI 0.765-0.827, p=< 0.0001).

What question did this study set out to answer?

To compare all-cause mortality, heart failure hospitalization, major adverse cardiovascular events, and chronic kidney disease progression between new users of eplerenone and spironolactone.

July 31, 2026Journal of Cardiovascular Medicine

In adults with heart failure, eplerenone was associated with lower all-cause mortality than spironolactone at 36 months (11.75% vs 14.58%; HR 0.795, 95% CI 0.765-0.827; P<0.0001).

Q: What are the key findings of this study?

Q: What question did this study set out to answer?

To compare all-cause mortality, heart failure hospitalization, major adverse cardiovascular events, and chronic kidney disease progression between new users of eplerenone and spironolactone.

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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?

Population

38 952 propensity score-matched pairs of adult new MRA users with heart failure

Comparison

Eplerenone vs spironolactone

Design

Retrospective, new-user propensity score-matched cohort study across 171 healthcare organizations

Follow-up

36 months

Key result

In adults with heart failure, eplerenone was associated with lower all-cause mortality than spironolactone at 36 months (11.75% vs 14.58%; HR 0.795, 95% CI 0.765-0.827; P<0.0001).

Authors

MAMustafa Abomohsen MAMohanad A. Alkuwaiti HAHamzah M. Alghzawi

Discussion

Member takes

Overview

May favor eplerenone over spironolactone for select HF outcomes; leaves open confirmation via randomized head-to-head trials.

Key Points

To compare all-cause mortality, heart failure hospitalization, major adverse cardiovascular events, and chronic kidney disease progression between new users of eplerenone and spironolactone.
Retrospective new-user cohort study utilizing the TriNetX Global Collaborative Network across 171 healthcare organizations.
Adults with heart failure receiving a first prescription for an MRA were matched 1:1 using propensity scores (N=77,904 total; 38,952 matched pairs) and followed for 36 months, with prespecified analyses in HFrEF and HFpEF.
At 36 months, eplerenone was associated with significantly lower all-cause mortality (11.75% vs. 14.58%; HR 0.795, 95% CI 0.765–0.827; P < 0.0001) compared with spironolactone.
Eplerenone was also associated with lower rates of heart failure hospitalization (HR 0.917, 95% CI 0.902–0.932), MACE (HR 0.900, 95% CI 0.886–0.915), and CKD progression (HR 0.803, 95% CI 0.745–0.867; all P < 0.0001).
In HFpEF, mortality did not differ significantly (HR 0.946, 95% CI 0.876–1.021; P = 0.162), while spironolactone was favored for MACE (HR 1.135, 95% CI 1.087–1.184) and hospitalization (HR 1.144, 95% CI 1.108–1.181; both P < 0.0001).

Study Design

Type

Cohort (n=77,904)

Multicenter

Yes

Structured PICO

Does eplerenone reduce all-cause mortality, heart failure hospitalization, MACE, and CKD progression compared to spironolactone in adults with heart failure?

Population

77,904 adults with heart failure receiving a first MRA prescription, matched 1:1 by propensity score, followed for 36 months.

Exposure

Eplerenone

Comparator

Spironolactone

Outcome

All-cause mortality, heart failure hospitalization, major adverse cardiovascular events (MACE), and chronic kidney disease (CKD) progression at 36 monthshard clinical

Main Result

Hazard Ratio: 0.795 (95% CI 0.765–0.827)

Absolute Event Rate: 11.75% vs 14.58%

p-value: p=< 0.0001

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.

Cite This Study

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 (11.75% vs 14.58%; HR 0.795, 95% CI 0.765-0.827; P<0.0001).

synapsesocial.com/papers/6aa25690a25963cecb139e3f https://doi.org/10.2459/jcm.0000000000001929

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July 31, 2026Journal of Cardiovascular Medicine

In adults with heart failure, eplerenone was associated with lower all-cause mortality than spironolactone at 36 months (11.75% vs 14.58%; HR 0.795, 95% CI 0.765-0.827; P<0.0001).

View Full Paper

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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?

Population

38 952 propensity score-matched pairs of adult new MRA users with heart failure

Comparison

Eplerenone vs spironolactone

Design

Retrospective, new-user propensity score-matched cohort study across 171 healthcare organizations

Follow-up

36 months

Key result

In adults with heart failure, eplerenone was associated with lower all-cause mortality than spironolactone at 36 months (11.75% vs 14.58%; HR 0.795, 95% CI 0.765-0.827; P<0.0001).

Authors

MAMustafa Abomohsen MAMohanad A. Alkuwaiti HAHamzah M. Alghzawi

Discussion

Member takes

Overview

May favor eplerenone over spironolactone for select HF outcomes; leaves open confirmation via randomized head-to-head trials.

Key Points

To compare all-cause mortality, heart failure hospitalization, major adverse cardiovascular events, and chronic kidney disease progression between new users of eplerenone and spironolactone.
Retrospective new-user cohort study utilizing the TriNetX Global Collaborative Network across 171 healthcare organizations.
Adults with heart failure receiving a first prescription for an MRA were matched 1:1 using propensity scores (N=77,904 total; 38,952 matched pairs) and followed for 36 months, with prespecified analyses in HFrEF and HFpEF.
At 36 months, eplerenone was associated with significantly lower all-cause mortality (11.75% vs. 14.58%; HR 0.795, 95% CI 0.765–0.827; P < 0.0001) compared with spironolactone.
Eplerenone was also associated with lower rates of heart failure hospitalization (HR 0.917, 95% CI 0.902–0.932), MACE (HR 0.900, 95% CI 0.886–0.915), and CKD progression (HR 0.803, 95% CI 0.745–0.867; all P < 0.0001).
In HFpEF, mortality did not differ significantly (HR 0.946, 95% CI 0.876–1.021; P = 0.162), while spironolactone was favored for MACE (HR 1.135, 95% CI 1.087–1.184) and hospitalization (HR 1.144, 95% CI 1.108–1.181; both P < 0.0001).

Study Design

Type

Cohort (n=77,904)

Multicenter

Yes

Structured PICO

Does eplerenone reduce all-cause mortality, heart failure hospitalization, MACE, and CKD progression compared to spironolactone in adults with heart failure?

Population

77,904 adults with heart failure receiving a first MRA prescription, matched 1:1 by propensity score, followed for 36 months.

Exposure

Eplerenone

Comparator

Spironolactone

Outcome

All-cause mortality, heart failure hospitalization, major adverse cardiovascular events (MACE), and chronic kidney disease (CKD) progression at 36 monthshard clinical

Main Result

Hazard Ratio: 0.795 (95% CI 0.765–0.827)

Absolute Event Rate: 11.75% vs 14.58%

p-value: p=< 0.0001

Cite This Study

synapsesocial.com/papers/6aa25690a25963cecb139e3f https://doi.org/10.2459/jcm.0000000000001929

Also Consider

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