title: Macitentan and morbidity and mortality in pulmonary arterial hypertension.
abstract: BACKGROUND
  Current therapies for pulmonary arterial hypertension have been adopted on the basis of short-term trials with exercise capacity as the primary end point. We assessed the efficacy of macitentan, a new dual endothelin-receptor antagonist, using a primary end point of morbidity and mortality in a long-term trial.
  
  
  METHODS
  We randomly assigned patients with symptomatic pulmonary arterial hypertension to receive placebo once daily, macitentan at a once-daily dose of 3 mg, or macitentan at a once-daily dose of 10 mg. Stable use of oral or inhaled therapy for pulmonary arterial hypertension, other than endothelin-receptor antagonists, was allowed at study entry. The primary end point was the time from the initiation of treatment to the first occurrence of a composite end point of death, atrial septostomy, lung transplantation, initiation of treatment with intravenous or subcutaneous prostanoids, or worsening of pulmonary arterial hypertension.
  
  
  RESULTS
  A total of 250 patients were randomly assigned to placebo, 250 to the 3-mg macitentan dose, and 242 to the 10-mg macitentan dose. The primary end point occurred in 46.4%, 38.0%, and 31.4% of the patients in these groups, respectively. The hazard ratio for the 3-mg macitentan dose as compared with placebo was 0.70 (97.5% confidence interval [CI], 0.52 to 0.96; P=0.01), and the hazard ratio for the 10-mg macitentan dose as compared with placebo was 0.55 (97.5% CI, 0.39 to 0.76; P<0.001). Worsening of pulmonary arterial hypertension was the most frequent primary end-point event. The effect of macitentan on this end point was observed regardless of whether the patient was receiving therapy for pulmonary arterial hypertension at baseline. Adverse events more frequently associated with macitentan than with placebo were headache, nasopharyngitis, and anemia.
  
  
  CONCLUSIONS
  Macitentan significantly reduced morbidity and mortality among patients with pulmonary arterial hypertension in this event-driven study. (Funded by Actelion Pharmaceuticals; SERAPHIN ClinicalTrials.gov number, NCT00660179.).
authors.affiliation: Cardiopulmonary Department, Ignacio Chávez National Heart Institute, Mexico City, Mexico. tpulido@prodigy.net.mx
authors.forename: Tomás
authors.initials: T
authors.lastname: Pulido
authors.forename: Igor
authors.initials: I
authors.lastname: Adzerikho
authors.forename: Richard N
authors.initials: RN
authors.lastname: Channick
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Galiè
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.forename: Pavel
authors.initials: P
authors.lastname: Jansa
authors.forename: Zhi-Cheng
authors.initials: ZC
authors.lastname: Jing
authors.forename: Franck-Olivier
authors.initials: FO
authors.lastname: Le Brun
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mehta
authors.forename: Camilla M
authors.initials: CM
authors.lastname: Mittelholzer
authors.forename: Loïc
authors.initials: L
authors.lastname: Perchenet
authors.forename: B K S
authors.initials: BK
authors.lastname: Sastry
authors.forename: Olivier
authors.initials: O
authors.lastname: Sitbon
authors.forename: Rogério
authors.initials: R
authors.lastname: Souza
authors.forename: Adam
authors.initials: A
authors.lastname: Torbicki
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zeng
authors.forename: Lewis J
authors.initials: LJ
authors.lastname: Rubin
authors.forename: Gérald
authors.initials: G
authors.lastname: Simonneau
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D017079:Exercise Tolerance; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D065130:Endothelin A Receptor Antagonists; D065131:Endothelin B Receptor Antagonists; D011743:Pyrimidines; D013449:Sulfonamides; C533860:macitentan