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September 15, 2026Current Medical Research and Opinion

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

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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.

Population

2,109 HFmrEF patients discharged alive

Comparison

No diuretics vs thiazide-only vs loop diuretic-only vs combined diuretic therapy

Design

Retrospective registry study

Follow-up

Median 30 months

Key result

Thiazide-only therapy was associated with lower long-term all-cause mortality (11%) compared to no diuretics (20%), whereas loop (39%) and combined diuretic therapy (48%) had higher mortality.

Authors

ASAlexander SchmittMBMichael BehnesMRMarielen Reinhardt

Discussion

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Overview

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

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%

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 (11%) compared to no diuretics (20%), whereas loop (39%) and combined diuretic therapy (48%) had higher mortality.

synapsesocial.com/papers/6aa94f569013453be30a26c2https://doi.org/10.1080/03007995.2026.2730837
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Also Consider

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

  1. 1Loop and thiazide diuretics and outcomes in heart failure with preserved ejection fraction2025 · 6 citations
  2. 2Current Clinical and Pharmacological Approaches to the Prescription of Loop Diuretics in Patients with Chronic Heart Failure2020 · 1 citations
  3. 3Combination Diuretic Therapy With Thiazides: A Systematic Review on the Beneficial Approach to Overcome Refractory Fluid Overload in Heart Failure2023 · 12 citations
  4. 4A Narrative Review on the Efficacy and Safety of Loop Diuretics in Patients With Heart Failure With Reduced Ejection Fraction and Preserved Ejection Fraction2023 · 5 citations
  5. 5Loop Diuretic Prescription and 30-Day Outcomes in Older Patients With Heart Failure2020 · 79 citations