Different diuretic regimes and long-term outcomes in heart failure with mildly reduced ejection fraction

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with mildly reduced ejection fraction (HFmrEF) (n=2109). Intervention: Thiazide-only, loop diuretic-only, or combined diuretic therapy vs. No diuretics. Primary outcome: All-cause mortality.

Q: What does this research mean for the field?

In patients with heart failure with mildly reduced ejection fraction (HFmrEF), thiazide-only diuretic therapy is associated with lower long-term mortality, whereas loop and combined diuretic therapies are associated with increased mortality and rehospitalization. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Alexander Schmitt; Michael Behnes; Marielen Reinhardt; Noah Abel; Felix Lau; K Weidner; Mohammad Abumayyaleh; Michael Hagmann; Ibrahim Akin; Tobias Schupp

doi:10.1080/03007995.2026.2730837

September 14, 2026Current Medical Research and Opinion

Different diuretic regimes and long-term outcomes in heart failure with mildly reduced ejection fraction

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Key result

Thiazide-only therapy linked to ~45% lower all-cause mortality vs no diuretics, unlike loop or combined diuretics.

n=2,109

Why the study?

Diuretics are commonly prescribed in heart failure, but prognostic data regarding their use in heart failure with mildly reduced ejection fraction remain limited.

Key Points

To investigate the prognostic impact of thiazide and loop diuretic regimens on long-term outcomes in patients with heart failure with mildly reduced ejection fraction.
Involved 2,109 consecutive hospitalized patients with heart failure with mildly reduced ejection fraction discharged alive from University Medical Centre Mannheim between 2016 and 2022 (HARMER registry, NCT05603390).
Patients were stratified at discharge by diuretic therapy: none, thiazide-only, loop diuretic-only, or combined diuretic therapy.
Tracked outcomes over a median follow-up of 30 months for primary endpoint of all-cause mortality and secondary endpoint of heart failure rehospitalization.
At discharge, 43% of patients received no diuretics, 9% received thiazides only, 40% received loop diuretics only, and 9% received combined diuretic therapy.
All-cause mortality at 30 months was lowest in the thiazide-only arm (11%) compared with no diuretics (20%), loop diuretics only (39%), and combined diuretic therapy (48%).
Loop diuretic monotherapy and combined diuretic therapy were associated with significantly increased rates of long-term mortality and heart failure-related rehospitalization.

Study Design

Type

Cohort (n=2,109)

Multicenter

No

PICO

P

Population

2,109 consecutive patients with heart failure with mildly reduced ejection fraction discharged alive, followed for a median of 30 months.

E

Exposure / Comparator

Thiazide-only, loop diuretic-only, or combined diuretic therapy vs No diuretics

O

Primary Outcome

All-cause mortality

Main Result

Absolute Event Rate: 11% vs 20%

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Implication

Diuretic use may mark higher risk in HFmrEF; leaves open causality and optimal strategies pending prospective trials.

Abstract

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Cite This Study

Schmitt et al. (2026) conducted a cohort in Heart failure with mildly reduced ejection fraction (HFmrEF) (n=2,109). Thiazide-only, loop diuretic-only, or combined diuretic therapy vs. No diuretics was evaluated on All-cause mortality. Thiazide-only therapy was associated with lower long-term all-cause mortality compared to no diuretics, whereas loop and combined diuretic therapy had higher mortality.

synapsesocial.com/papers/6aa94f569013453be30a26c2 https://doi.org/10.1080/03007995.2026.2730837

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Different diuretic regimes and long-term outcomes in heart failure with mildly reduced ejection fraction

Key Points

Study Design

PICO

Main Result

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Different diuretic regimes and long-term outcomes in heart failure with mildly reduced ejection fraction

Key Points

Study Design

PICO

Main Result

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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