Key takeaways
- Beforehand, the mix of hydralazine with isosorbide dinitrate was related to lowered mortality in Black sufferers with coronary heart failure and lowered ejection fraction.
- Within the H-HeFT trial, no important distinction was noticed with hydralazine–isosorbide dinitrate vs. placebo for loss of life or coronary heart failure occasions.
- Therapy discontinuation charges have been excessive, emphasising the necessity for cautious consideration of the tolerability profile of hydralazine–isosorbide dinitrate in medical follow.
Munich, Germany – 30 August 2026: In sufferers with coronary heart failure, hydralazine with isosorbide dinitrate didn’t considerably enhance the incidence of loss of life or coronary heart failure occasions and therapy discontinuation charges have been excessive. These have been the principle findings of the H-HeFT trial introduced in a Sizzling Line session immediately at ESC Congress 2026.[1]
Coronary heart failure stays a typical and lethal illness. Principal Investigator, Professor Lars Køber from Rigshospitalet – Copenhagen College Hospital, Copenhagen, Denmark, defined that the H-HeFT trial was performed to evaluate whether or not an present drug may convey advantages to a wider inhabitants. “Over 20 years in the past, the A-HeFT research demonstrated a 43% discount in mortality with the mix of hydralazine with isosorbide dinitrate (H-ISDN) when given on prime of established coronary heart failure remedy at the moment,[2]” he famous. “The research inhabitants consisted of Black sufferers with coronary heart failure and lowered ejection fraction and the H-ISDN mixture has by no means been examined extra broadly. The H-HeFT trial was designed to additional consider H-ISDN in sufferers with coronary heart failure.”
The investigator-initiated, double-blind H-HeFT trial was performed in 23 centres in Denmark as a part of DANHEART. DANHEART had a factorial design, evaluating H-ISDN in sufferers with continual coronary heart failure (H-HeFT trial) and metformin in sufferers with continual coronary heart failure and diabetes or prediabetes (Met-HeFT trial; additionally introduced at ESC Congress 2026[3]).
Within the H-HeFT trial, eligible sufferers had symptomatic continual coronary heart failure, a left ventricular ejection fraction of as much as 40% and have been required to have systolic blood strain of not less than 100 mmHg and elevated ranges of a coronary heart pressure marker (NT-proBNP >350 pg/mL or BNP >80 pg/mL). A complete of 592 members have been randomised (1:1) to twice-daily hydralazine 37.5 mg plus isosorbide dinitrate 20 mg (with uptitration) or matching placebo. The imply age was round 70 years and roughly 17% have been girls. The first endpoint was a composite of loss of life, worsening coronary heart failure, an pressing outpatient go to leading to intravenous remedy or metolazone remedy for coronary heart failure, coronary heart transplantation or left ventricular help system implantation.
Over follow-up of as much as seven years, there was no important distinction between H-ISDN and placebo for the first endpoint (8.6 occasions/100 patient-years vs. 9.3 occasions/100 patient-years; hazard ratio [HR] 0.90; 95% confidence interval [CI] 0.67 to 1.21). All-cause loss of life occurred in 19.4% of sufferers within the H-ISDN group and 24.2% of sufferers within the placebo group (HR 0.72; 95% CI 0.51 to 1.02).
Professor Køber commented that the outcomes of the trial might have been impacted by the excessive variety of sufferers who discontinued H-ISDN therapy, though there didn’t seem like any security issues. “Whether or not there may very well be a discount in mortality with H-ISDN requires a brand new randomised managed trial,” he stated.
Additionally on the congress, Physician Jawad Haider Butt, from the identical establishment, introduced a meta-analysis of three trials evaluating H-ISDN therapy, together with A-HeFT and H-HeFT.4 Information from 2,101 sufferers with coronary heart failure have been analysed. H-ISDN was related to a discount in all-cause loss of life (HR 0.71; 95% CI 0.58 to 0.87) and cardiovascular loss of life (HR 0.65; 95% CI 0.47 to 0.90), however outcomes on hospitalisations for coronary heart failure have been inconsistent. Substantial variations in trial design, length of follow-up and background therapies have been famous throughout the trials. “Given the heterogeneity and the tolerability points, it’s troublesome to make agency conclusions on the impact of H-ISDN on cardiovascular outcomes,” concluded Physician Butt.
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