Macitentan and Morbidity and Mortality in Pulmonary Arterial Hypertension

• Published in: The New England journal of medicine Vol. 369; no. 9; pp. 809 - 818
• Main Authors: Pulido, Tomás, Adzerikho, Igor, Channick, Richard N, Delcroix, Marion, Galiè, Nazzareno, Ghofrani, Hossein-Ardeschir, Jansa, Pavel, Jing, Zhi-Cheng, Le Brun, Franck-Olivier, Mehta, Sanjay, Mittelholzer, Camilla M, Perchenet, Loïc, Sastry, B.K.S, Sitbon, Olivier, Souza, Rogério, Torbicki, Adam, Zeng, Xiaofeng, Rubin, Lewis J, Simonneau, Gérald
• Format: Journal Article
• Language: English
• Published: Waltham, MA Massachusetts Medical Society 29.08.2013
• Subjects: Adult; Biological and medical sciences; Clinical outcomes; Clinical trials; Double-Blind Method; Drug dosages; Endothelin A Receptor Antagonists; Endothelin B Receptor Antagonists; Endothelins; Epidemiology; Exercise Tolerance; Familial Primary Pulmonary Hypertension; Female; General aspects; Headache; Heart failure; Hospitalization - statistics & numerical data; Humans; Hypertension; Hypertension, Pulmonary - complications; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - mortality; Intravenous administration; Intubation; Kaplan-Meier Estimate; Laboratories; Lung transplantation; Male; Medical sciences; Middle Aged; Morbidity; Mortality; Patients; Pharmaceuticals; Pneumology; Prostaglandins; Public health. Hygiene; Public health. Hygiene-occupational medicine; Pulmonary hypertension; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Pyrimidines - adverse effects; Pyrimidines - therapeutic use; Rhinopharyngitis; Substance abuse treatment; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Mexico; Medicine; Respiratory disease; Blood vessel; Mortality; Cardiovascular disease; Circulatory system; Epidemiology; Artery; Pulmonary hypertension; Morbidity
• ISSN: 0028-4793; 1533-4406; 1533-4406
• DOI: 10.1056/NEJMoa1213917

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 . . .