{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:56:50Z","timestamp":1790834210124,"version":"4.1.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T00:00:00Z","timestamp":1568246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Glaxo Smith Kline"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Initial combination therapy with ambrisentan and tadalafil reduced the risk of clinical failure events for treatment-na\u00efve participants with pulmonary arterial hypertension (PAH) as compared to monotherapy. Previous studies in PAH have demonstrated greater treatment benefits in more symptomatic participants.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>AMBITION was an event-driven, double-blind study in which participants were randomized 2:1:1 to once-daily initial combination therapy with ambrisentan 10\u2009mg plus tadalafil 40\u2009mg, ambrisentan 10\u2009mg plus placebo, or tadalafil 40\u2009mg plus placebo. In this pre-specified subgroup analysis, we compared the efficacy data between those with functional class (FC) II vs. FC III symptoms at baseline.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>This analysis included 500 participants in the previously defined primary analysis set (<jats:italic>n<\/jats:italic>\u2009=\u2009155 FC II, <jats:italic>n<\/jats:italic>\u2009=\u2009345 FC III). Comparing combination therapy to pooled monotherapy, the risk of clinical failure events was reduced by 79% (hazard ratio, 0.21 [95% confidence interval: 0.071, 0.63]) for FC II patients and 42% (hazard ratio, 0.58 [95% confidence interval: 0.39, 0.86]) for FC III patients. In a post-hoc analysis, the risk of first hospitalization for worsening PAH was also reduced by combination therapy, particularly for FC II patients (0 combination vs. 11 [14%] pooled monotherapy). Adverse events were frequent but comparable between the subgroups.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Treatment benefit from initial combination therapy appeared at least as great for FC II as for FC III participants. Hospitalizations for worsening PAH were not observed in FC II participants assigned to combination. The present data support an initial combination strategy for newly diagnosed patients even when symptoms are less severe.<\/jats:p>\n                <jats:p>Funded by Gilead Sciences, Inc. and GlaxoSmithKline; AMBITION <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> number, NCT01178073.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-019-1180-1","type":"journal-article","created":{"date-parts":[[2019,9,12]],"date-time":"2019-09-12T04:27:04Z","timestamp":1568262424000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Clinical outcomes stratified by baseline functional class after initial combination therapy for pulmonary arterial hypertension"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1399-5206","authenticated-orcid":false,"given":"R. 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SR received remunerations for lectures and\/or consultancy from Abbott, Actelion, Arena, Bayer, BMS, MSD, Novartis, Pfizer, and United Therapeutics; his institution received research grants from Actelion, Bayer, Novartis, and United Therapeutics. AEF received remunerations for lectures and\/or consultancy from United Therapeutics, Actelion, Gilead Sciences, for participation as study Endpoint Adjudication or Safety Committees from United Therapeutics, & Complexa. EG received speaker honoraria\/consultancy fees from Actelion, Bayer\/MSD, Orpha Swiss GmbH, Medscape, his institution received research grants from Actelion, Bayer\/MSD, GSK, Bial, United Therapeutics, Novartis, Bellerophon, OMT, Pfizer, Reata. MMC received remunerations for lectures and\/or consultancy totaling < $10,000 annually from Actelion, Bayer, Gilead, United Therapeutics, Reata, Arena, Medscape, Express Scripts, and Phase Bio; his institution received research grants from Actelion, Bayer, Gilead, Medtronic, Eiger, Liquidia, Arena, and Phase Bio. RJO has received speaker\/consulting honoraria from Actelion, Arena, Gilead, Medscape, Medtronic, Reata, and United Therapeutics; his institution received research grants from AAdi, Actelion, Arena, Gilead, GSK, Liquidia, Reata, and United Therapeutics. JL was an employee of GSK during the conduct of the study and the preparation of the manuscript. CB is an employee of Gilead with equity interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"208"}}