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

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.

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.

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).

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%.