H-ISDN meta-analysis

H-ISDN meta-analysis

Patient / Population Intervention / Exposure Comparison Outcome

In patients with HFrEF in randomised trials of hydralazine–isosorbide dinitrate, hydralazine–isosorbide dinitrate reduced clinical outcomes compared with control.

N

2,101patients

Design

systematic review and meta-analysis of randomised trials of hydralazine–isosorbide dinitrate in heart failure with reduced ejection fraction, as listed in the programme; protocol not public

Endpoint

Pooled outcomes: all-cause death, cardiovascular death, and hospitalisation for heart failure

Relevance

2Important — one of several pillars.

ResultPooling V-HeFT I (n = 459), A-HeFT (n = 1,050) and H-HeFT (n = 592): all-cause death HR 0.71 (95% CI 0.58-0.87; P = 0.001, I2 = 0%), cardiovascular death HR 0.65 (0.47-0.90; P = 0.009). First heart failure hospitalisation HR 0.71 (0.56-0.89) in fixed-effect models but with substantial heterogeneity (I2 = 72.5%), and not significant under random effects. A Mantel-Haenszel sensitivity analysis put death at RR 0.82 (0.69-0.98).

Butt JH, et al. Presented at ESC Congress 2026, Hot Line 6, 30 August. PROSPERO CRD420261402397.

Discussion & critique

Three trials forty years apart, pooled to buy the power none of them had: the mortality signal is consistent (I2 = 0%) and survives a Mantel-Haenszel check, which is the strongest case yet for a drug pair the guidelines restrict to one group of patients. The hospitalisation result is the weak half — it holds only under fixed effects, and the heterogeneity behind it is real: A-HeFT stopped early for benefit, H-HeFT saw no effect at all. The trials also differ in what background therapy meant, from digitalis and diuretics in 1980 to four-pillar therapy in 2025, so the pooled estimate answers a question no single era asked.