The safety and efficacy of adding Bosentan ( Tracleer ) to Sildenafil ( Revatio ) in pulmonary arterial hypertension ( PAH ) patients was investigated.
In this prospective, double-blind, event-driven trial, symptomatic PAH patients receiving stable Sildenafil ( greater than or equal to 20 mg three times daily ) for greater than or equal to 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, HR=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. ( Xagena )
McLaughlin V et al, Eur Respir J 2015;46:414-421