title: Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension.
abstract: The safety and efficacy of adding bosentan to sildenafil in pulmonary arterial hypertension (PAH) patients was investigated.In this prospective, double-blind, event-driven trial, symptomatic PAH patients receiving stable sildenafil (≥20 mg three times daily) for ≥3 months were randomised (1:1) to placebo or bosentan (125 mg twice daily). The composite primary end-point was the time to the first morbidity/mortality event, defined as all-cause death, hospitalisation for PAH worsening or intravenous prostanoid initiation, atrial septostomy, lung transplant, or PAH worsening. Secondary/exploratory end-points included change in 6-min walk distance and World Health Organization functional class at 16 weeks, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) over time, and all-cause death.Overall, 334 PAH patients were randomised to placebo (n=175) or bosentan (n=159). A primary end-point event occurred in 51.4% of patients randomised to placebo and 42.8% to bosentan (hazard ratio 0.83, 97.31% CI 0.58-1.19; p=0.2508). The mean between-treatment difference in 6-min walk distance at 16 weeks was +21.8 m (95% CI +5.9-37.8 m; p=0.0106). Except for NT-proBNP, no difference was observed for any other end-point. The safety profile of bosentan added to sildenafil was consistent with the known bosentan safety profile.In COMPASS-2, adding bosentan to stable sildenafil therapy was not superior to sildenafil monotherapy in delaying the time to the first morbidity/mortality event.
authors.affiliation: Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA vmclaugh@umich.edu.
authors.forename: Vallerie
authors.initials: V
authors.lastname: McLaughlin
authors.affiliation: Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Richard N
authors.initials: RN
authors.lastname: Channick
authors.affiliation: University of Giessen and Marburg Lung Center, Giessen, Germany.
authors.forename: Hossein-Ardeschir
authors.initials: HA
authors.lastname: Ghofrani
authors.affiliation: Department of Statistics, Effi-Stat, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lemarié
authors.affiliation: Department of Cardiology, Erasme University Hospital, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Naeije
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Milton
authors.initials: M
authors.lastname: Packer
authors.affiliation: Pulmonary Department, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Rogério
authors.initials: R
authors.lastname: Souza
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: Victor F
authors.initials: VF
authors.lastname: Tapson
authors.affiliation: Global Medical Affairs, Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Tolson
authors.affiliation: Department of Cardiology, IKEM, Prague, Czech Republic.
authors.forename: Hikmet
authors.initials: H
authors.lastname: Al Hiti
authors.affiliation: Complexo Hospitalar Santa Casa De Porto Alegre, Pulmonary Vascular Research Institute, Porto Alegre, Brazil.
authors.forename: Gisela
authors.initials: G
authors.lastname: Meyer
authors.affiliation: Department of Respiratory Medicine, Hannover Medical School and German Center of Lung Research (DZL), Hannover, Germany.
authors.forename: Marius M
authors.initials: MM
authors.lastname: Hoeper
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000077300:Bosentan; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000068677:Sildenafil Citrate / Q000008:administration & dosage* / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage* / Q000627:therapeutic use; D013557:Switzerland; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D013449:Sulfonamides; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000077300:Bosentan