H-ISDN meta-analysis

H-ISDN meta-analysis

Patient / Population Intervention / Exposition Comparaison Critère de jugement

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

N

2 101patients

Schéma

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

Critère

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

Pertinence

2Important — l’un des piliers parmi d’autres.

RésultatPooling 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 et 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.