Pulmonary hypertension · Endothelin receptor antagonists
Macitentan and morbidity and mortality in pulmonary arterial hypertension
| Design | Event-driven, randomised, double-blind, placebo-controlled trial |
|---|---|
| Treatment | Macitentan 3 mg or 10 mg once daily |
| Control | Placebo |
| Population | 742 patients with pulmonary arterial hypertension, many on background therapy |
| Follow-up | Event-driven, median approximately 2 years |
| Primary endpoint | Time to first morbidity or mortality event |
| Result | The primary endpoint occurred in 46.4% on placebo, 38.0% on macitentan 3 mg and 31.4% on 10 mg. Hazard ratio 0.70 (97.5% CI 0.52 to 0.96, p=0.01) for 3 mg and 0.55 (0.39 to 0.76, p<0.001) for 10 mg. Worsening of pulmonary arterial hypertension was the most frequent event. |
| Secondary endpoints | Six-minute walk distance, WHO functional class, death or hospitalisation for PAH |
Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study.
The trial authors, in the published abstract
The trial that moved pulmonary hypertension away from six-minute walk distance towards event-driven outcomes, which is why it remains a reference point. Combined with GRIPHON it established that long-term outcome trials in this disease are feasible, paving the way for AMBITION and later ZENITH.
Pulido T, Adzerikho I, Channick RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 2013 Aug 29;369(9):809-18.