Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension

Vallerie McLaughlin, Richard N. Channick, Hossein Ardeschir Ghofrani, Jean Christophe Lemarié, Robert Naeije, Milton Packer, Rogério Souza, Victor F. Tapson, Jonathan Tolson, Hikmet Al Hiti, Gisela Meyer, Marius M. Hoeper

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122 Scopus citations

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 endpoint 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.

Original languageEnglish (US)
Pages (from-to)405-413
Number of pages9
JournalEuropean Respiratory Journal
Volume46
Issue number2
DOIs
StatePublished - Aug 1 2015

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    McLaughlin, V., Channick, R. N., Ghofrani, H. A., Lemarié, J. C., Naeije, R., Packer, M., Souza, R., Tapson, V. F., Tolson, J., Al Hiti, H., Meyer, G., & Hoeper, M. M. (2015). Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension. European Respiratory Journal, 46(2), 405-413. https://doi.org/10.1183/13993003.02044-2014