Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension

Eur Respir J. 2015 Aug;46(2):405-13. doi: 10.1183/13993003.02044-2014. Epub 2015 Jun 25.


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.

Trial registration: NCT00303459.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / therapeutic use
  • Bosentan
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Male
  • Middle Aged
  • Prospective Studies
  • Sildenafil Citrate / administration & dosage*
  • Sildenafil Citrate / therapeutic use
  • Sulfonamides / administration & dosage*
  • Sulfonamides / therapeutic use
  • Switzerland
  • Treatment Outcome
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / therapeutic use


  • Antihypertensive Agents
  • Sulfonamides
  • Vasodilator Agents
  • Sildenafil Citrate
  • Bosentan

Associated data