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.

Complexo Hospitalar Santa Casa De Porto Alegre Pulmonary Vascular Research Institute Porto Alegre Brazil

Department of Cardiology Erasme University Hospital Brussels Belgium

Department of Cardiology IKEM Prague Czech Republic

Department of Clinical Sciences University of Texas Southwestern Medical Center Dallas TX USA

Department of Internal Medicine Division of Cardiovascular Medicine University of Michigan Ann Arbor MI USA

Department of Respiratory Medicine Hannover Medical School and German Center of Lung Research Hannover Germany

Department of Statistics Effi Stat Paris France

Division of Pulmonary and Critical Care Medicine Cedars Sinai Medical Center Los Angeles CA USA

Global Medical Affairs Actelion Pharmaceuticals Ltd Allschwil Switzerland

Pulmonary and Critical Care Massachusetts General Hospital Boston MA USA

Pulmonary Department Heart Institute University of São Paulo Medical School São Paulo Brazil

University of Giessen and Marburg Lung Center Giessen Germany

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Eur Respir J. 2015 Aug;46(2):297-8. doi: 10.1183/13993003.00907-2015. PubMed

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NCT00303459