Hydralazine-isosorbide dinitrate in chronic heart failure with reduced ejection fraction: the H-HeFT trial

Why clinicians should know about it

• Picked for Cardiology and Cardiovascular Medicine (paper of the day, 6 November 2026): Hydralazine‑isosorbide dinitrate did not change composite HF endpoint

Abstract

BACKGROUND AND AIMS: Hydralazine-isosorbide dinitrate (H-ISDN) has shown benefit in earlier randomized trials of patients with reduced left ventricular ejection fraction (LVEF) and chronic heart failure. This trial tested if H-ISDN could reduce worsening heart failure or mortality in patients with chronic heart failure with reduced ejection fraction (HFrEF) receiving contemporary treatment. METHODS: The Hydralazine-Isosorbide Dinitrate in Patients With Chronic Heart Failure Trial (H-HeFT) was a multicentre, randomized (1:1), double-blind, placebo-controlled trial in patients with HFrEF at 23 Danish hospitals (New York Heart Association class II-IV, elevated N-terminal pro-B-type natriuretic peptide and LVEF ≤40%). Target treatment was hydralazine 75 mg/isosorbide dinitrate 40 mg three times a day (t.i.d). The primary endpoint was a composite of hospitalization with worsening heart failure, an urgent outpatient visit resulting in intravenous/metolazone therapy for heart failure, heart transplantation, left ventricular assist device implantation, or death. Secondary endpoints included components of the primary outcome. RESULTS: Overall, 592 predominantly White patients (median age 72 years, 18% women) were randomized with a mean follow-up of 3.7 years. The primary outcome occurred in 90 of 294 patients (30.6%) in the H-ISDN group and in 91 of 298 patients (30.5%) in the placebo group [hazard ratio (HR) 0.90; 95% confidence interval (CI) 0.67-1.21; P = .48]. There were 57 deaths in the H-ISDN group vs 72 in the placebo group (HR 0.72; 95% CI 0.51-1.02); worsening heart failure events occurred in 52 vs 47 patients (HR 1.01; 95% CI 0.68-1.50). CONCLUSIONS: Hydralazine-isosorbide dinitrate did not change the incidence of the composite endpoint of heart failure events or death in patients with heart failure and LVEF ≤40%.

Abstract as published, via PubMed.