{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:28:13Z","timestamp":1793831293740,"version":"4.6.1"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100011891","name":"Cardiovascular Medical Research and Education Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011891","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K24 HL103844"],"award-info":[{"award-number":["K24 HL103844"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["; K23 HL141584"],"award-info":[{"award-number":["; K23 HL141584"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 HL007891"],"award-info":[{"award-number":["T32 HL007891"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>Effective therapies that target three main signalling pathways are approved to treat pulmonary arterial hypertension (PAH). However, there are few large patient-level studies that compare the effectiveness of these pathways. The aim of this analysis was to compare the effectiveness of the treatment pathways in PAH and to assess treatment heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A network meta-analysis was performed using individual participant data of 6811 PAH patients from 20 Phase III randomized clinical trials of therapy for PAH that were submitted to the US Food and Drug Administration. Individual drugs were grouped by the following treatment pathways: endothelin, nitric oxide, and prostacyclin pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The mean (\u00b1standard deviation) age of the sample was 49.2 (\u00b115.4) years; 78.4% were female, 59.7% had idiopathic PAH, and 36.5% were on background PAH therapy. After covariate adjustment, targeting the endothelin + nitric oxide pathway {\u03b2: 43.7\u2005m [95% confidence interval (CI): 32.9, 54.4]}, nitric oxide pathway [\u03b2: 29.4\u2005m (95% CI: 22.6, 36.3)], endothelin pathway [\u03b2: 25.3\u2005m (95% CI: 19.8, 30.8)], and prostacyclin pathway [oral\/inhaled \u03b2: 19.1\u2005m (95% CI: 14.2, 24.0), intravenous\/subcutaneous \u03b2: 24.4\u2005m (95% CI: 15.1, 33.7)] significantly increased 6\u2005min walk distance at 12 or 16 weeks compared with placebo. Treatments also significantly reduced the likelihood of having clinical worsening events. There was significant heterogeneity of treatment effects by age, body mass index, hypertension, diabetes, and coronary artery disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Drugs targeting the three traditional treatment pathways significantly improve outcomes in PAH, with significant treatment heterogeneity in patients with some comorbidities. Randomized clinical trials are warranted to identify the most effective treatment strategies in a personalized approach.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehae049","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T00:10:50Z","timestamp":1707264650000},"page":"1937-1952","source":"Crossref","is-referenced-by-count":33,"title":["Pulmonary arterial hypertension treatment: an individual participant data network meta-analysis"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4892-9471","authenticated-orcid":false,"given":"Jude","family":"Moutchia","sequence":"first","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn L","family":"McClelland","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health, University of Washington , Seattle, WA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Al-Naamani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina H","family":"Appleby","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H","family":"Holmes","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasleen","family":"Minhas","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold I","family":"Palevsky","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey E","family":"Ventetuolo","sequence":"additional","affiliation":[{"name":"Department of Medicine and Health Services, Policy and Practice, Brown University , Providence, RI , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M","family":"Kawut","sequence":"additional","affiliation":[{"name":"Department of Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"2024060106515841300_ehae049-B1","doi-asserted-by":"crossref","first-page":"1801887","DOI":"10.1183\/13993003.01887-2018","article-title":"Pathology and pathobiology of pulmonary hypertension: state of the art and research perspectives","volume":"53","author":"Humbert","year":"2019","journal-title":"Eur Respir J"},{"key":"2024060106515841300_ehae049-B2","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1056\/NEJMra2000348","article-title":"Pulmonary arterial hypertension","volume":"385","author":"Hassoun","year":"2021","journal-title":"N Engl J Med"},{"key":"2024060106515841300_ehae049-B3","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension: developed by the task force for the diagnosis and treatment of pulmonary hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS). 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