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

Diuretics are commonly prescribed for patients with heart failure (HF), yet prognostic data in HF with mildly reduced ejection fraction (HFmrEF) remain limited. This study investigates the prognostic impact of thiazide and loop diuretics in HFmrEF.

Consecutive HFmrEF patients hospitalized at the University Medical Centre Mannheim between 2016 and 2022 were retrospectively included (HARMER registry, clinicaltrials.gov identifier: NCT05603390) and stratified by diuretic therapy at discharge: none (N), thiazide-only (T), loop diuretic-only (L), or combined diuretic therapy (T + L). The primary endpoint was all-cause mortality at 30 months (median follow-up), secondary endpoint was HF-related rehospitalization.

Among 2,109 HFmrEF patients discharged alive, 43% received no diuretics, 9% thiazides only, 40% loop diuretics only, and 9% combined diuretic therapy. Thiazide-only patients had the lowest of long-term all-cause mortality (11%) compared to no diuretics (20%), while patients with loop (39%), and combined diuretic therapy (48%) had higher long-term mortality rates (log-rank p = 0.001). HF-rehospitalization rates followed a similar pattern (N: 5% and T: 7% vs. L: 21% and L + T: 31%, p = 0.001). After multivariable adjustment, thiazide-only therapy remained associated with lower mortality (HR = 0.515, p = 0.009), while loop and combined diuretic therapy were associated with increased mortality (L: HR = 1.299, p = 0.031; T + L: HR = 1.702, p = 0.001) and HF-rehospitalization (L: HR = 1.998, p = 0.001; T + L: HR = 2.535, p = 0.001).

In HFmrEF, thiazide-only therapy was associated with the lowest mortality, while loop and combined diuretic therapy were linked to increased mortality and HF-rehospitalization. Randomized trials investigating long-term diuretic therapy in HFmrEF patients are needed.