{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:57:39Z","timestamp":1790834259865,"version":"4.1.0"},"reference-count":19,"publisher":"European Respiratory Society (ERS)","issue":"2","funder":[{"DOI":"10.13039\/100005646","name":"Actelion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2015,4,30]]},"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>The safety and efficacy of adding bosentan to sildenafil in pulmonary arterial hypertension (PAH) patients was investigated.<\/jats:p><jats:p>In this prospective, double-blind, event-driven trial, symptomatic PAH patients receiving stable sildenafil (\u226520\u2005mg three times daily) for \u22653\u2005months were randomised (1:1) to placebo or bosentan (125\u2005mg 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\u2005weeks, change in N-terminal pro-brain natriuretic peptide (NT-proBNP) over time, and all-cause death.<\/jats:p><jats:p>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\u20131.19; p=0.2508). The mean between-treatment difference in 6-min walk distance at 16\u2005weeks was +21.8\u2005m (95% CI +5.9\u201337.8\u2005m; 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.<\/jats:p><jats:p>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.<\/jats:p>","DOI":"10.1183\/13993003.02044-2014","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T16:27:09Z","timestamp":1435940829000},"page":"405-413","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":189,"title":["Bosentan added to sildenafil therapy in patients with pulmonary arterial hypertension"],"prefix":"10.1183","volume":"46","author":[{"given":"Vallerie","family":"McLaughlin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard N.","family":"Channick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossein-Ardeschir","family":"Ghofrani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Lemari\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Naeije","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton","family":"Packer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rog\u00e9rio","family":"Souza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor F.","family":"Tapson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Tolson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikmet","family":"Al Hiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius M.","family":"Hoeper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2015,6,25]]},"reference":[{"key":"2024102023360428000_46.2.405.1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040291"},{"key":"2024102023360428000_46.2.405.2","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00004812"},{"key":"2024102023360428000_46.2.405.3","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00007011"},{"key":"2024102023360428000_46.2.405.4","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00007314"},{"key":"2024102023360428000_46.2.405.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1213917"},{"key":"2024102023360428000_46.2.405.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.038"},{"key":"2024102023360428000_46.2.405.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.010"},{"key":"2024102023360428000_46.2.405.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2013.12.179"},{"key":"2024102023360428000_46.2.405.9","unstructured":"Actelion Pharmaceuticals UK Ltd. Tracleer (bosentan) 62.5mg film-coated tablets. www.medicines.org.uk\/emc\/medicine\/20422\/SPC\/Tracleer+(bosentan)+62%205mg+film-coated+tablets\/ Date last accessed: September, 2014. Date last updated: January, 2015."},{"key":"2024102023360428000_46.2.405.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(01)06250-X"},{"key":"2024102023360428000_46.2.405.11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa012212"},{"key":"2024102023360428000_46.2.405.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60919-8"},{"key":"2024102023360428000_46.2.405.13","doi-asserted-by":"publisher","DOI":"10.1097\/01.smj.0000217927.81107.65"},{"key":"2024102023360428000_46.2.405.14","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.04.00051104"},{"key":"2024102023360428000_46.2.405.15","unstructured":"EU Clinical Trials Register. 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