In an event-driven trial, macitentan (an endothelin-receptor antagonist) at a dose of 3 or 10 mg was compared with placebo in patients with symptomatic pulmonary arterial hypertension. At a median of 115 weeks, both macitentan doses were associated with reduced morbidity and mortality. Pulmonary arterial hypertension, a severe disease characterized by a sustained elevation of pulmonary vascular resistance, ultimately leads to right heart failure and death. 1 Disease progression occurs despite the availability of drugs that are specific for the disorder. 2 Endothelin-receptor antagonists, phosphodiesterase type 5 inhibitors, and prostacyclin and its analogues have been approved for the treatment of pulmonary arterial hypertension and adopted clinically on the basis of short-term trials (12 to 16 weeks) that have shown improvements in exercise capacity as measured by the distance walked in 6 minutes. 3 – 10 However, current guidelines suggest that the primary end point in phase 3 . . .