{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:05:56Z","timestamp":1792782356742,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":518,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Actelion Pharmaceuticals Ltd, a Johnson & Johnson Company","id":[{"id":"https:\/\/ror.org\/04qkyeg11","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,11,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>According to current guidelines, initial monotherapy should be considered for pulmonary arterial hypertension (PAH) patients with cardiopulmonary comorbidities. This analysis of combined data from the TRITON and REPAIR clinical trials, assesses efficacy and safety of initial double combination therapy in patients without vs. with 1\u20132 cardiac comorbidities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Data were combined for patients from TRITON (NCT02558231) and REPAIR (NCT02310672) on initial macitentan and tadalafil double combination therapy (overall set, n\u2009=\u2009148) and two subgroups defined as patients without cardiac comorbidities (n\u2009=\u200962) and those with 1\u20132 cardiac comorbidities (n\u2009=\u200978). Patients with \u22653 comorbidities were excluded from these studies. For the overall set, the median (Q1\u2013Q3) duration of combined macitentan and tadalafil exposure was 513.0 (364.0\u2013778.0) days, and was similar between subgroups. Change from baseline to Week 26 for pulmonary vascular resistance was \u221255% and \u221250% for patients without and with 1\u20132 cardiac comorbidities, respectively; marked improvements in other hemodynamic and functional parameters were also observed, although functional parameters improved to a lesser extent in patients with comorbidities. At Week 26, the majority of patients had improved PAH risk status, according to the non-invasive four-strata and REVEAL Lite 2.0 methods. The safety profile of initial macitentan plus tadalafil combination therapy was consistent with the known profiles of the two drugs, and similar between the subgroups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Initial double combination therapy with macitentan plus tadalafil is efficacious in patients with PAH with 1\u20132 cardiac comorbidities and those without, with similar safety and tolerability profiles between the two groups.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3319","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T04:59:27Z","timestamp":1720155567000},"page":"2379-2391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Initial Combination Therapy with Macitentan and Tadalafil in Patients with Pulmonary Arterial Hypertension, with and without Cardiac Comorbidities"],"prefix":"10.1093","volume":"26","author":[{"given":"Vallerie V.","family":"McLaughlin","sequence":"first","affiliation":[{"name":"University of Michigan , Ann Arbor, MI ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Sitbon","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, H\u00f4pital Bic\u00eatre , Le Kremlin Bic\u00eatre ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Chin","sequence":"additional","affiliation":[{"name":"UT Southwestern Medical Center , Dallas, TX ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazzareno","family":"Gali\u00e8","sequence":"additional","affiliation":[{"name":"Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna , Bologna ,","place":["Italy"]},{"name":"Dipartimento DIMEC, Universit\u00e0 di Bologna , Bologna ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius M.","family":"Hoeper","sequence":"additional","affiliation":[{"name":"Hannover Medical School and German Centre for Lung Research , Hannover ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Kiely","sequence":"additional","affiliation":[{"name":"Sheffield Pulmonary Vascular Disease Unit, NIHR Biomedical Research Centre Sheffield and University of Sheffield , Sheffield ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwen","family":"MacDonald","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd, a Johnson & Johnson Company, Global Medical Affairs , Allschwil ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Martin","sequence":"additional","affiliation":[{"name":"Actelion Pharmaceuticals Ltd, a Johnson & Johnson Company, Statistical Decision Science , Allschwil ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Mathai","sequence":"additional","affiliation":[{"name":"Johns Hopkins University School of Medicine , Baltimore, MD ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Peacock","sequence":"additional","affiliation":[{"name":"Scottish Pulmonary Vascular Unit , Glasgow ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Tawakol","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School , Boston, MA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Torbicki","sequence":"additional","affiliation":[{"name":"Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre of Postgraduate Medical Education, ECZ-Otwock, ERN-LUNG 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