{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:43:11Z","timestamp":1790703791663,"version":"4.1.0"},"reference-count":24,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Respir Dis"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Pulmonary arterial hypertension (PAH) remains progressive despite contemporary background therapy. Sotatercept is a novel activin signaling inhibitor that targets pulmonary vascular remodeling and may improve clinical and hemodynamic outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To evaluate the efficacy, hemodynamic effects, and safety of sotatercept in patients with PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>Systematic review and meta-analysis of randomized controlled trials (RCTs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources and methods:<\/jats:title>\n                    <jats:p>Five electronic databases were searched through October 2, 2025, for eligible RCTs. Time-to-event outcomes were analyzed using pooled individual patient data with hazard ratios (HRs), while secondary outcomes were assessed using random-effects risk ratios (RRs) and mean differences (MDs), with 95% confidence intervals (CI). Trial-sequential analysis (TSA) evaluated the conclusiveness of results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In four RCTs (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u2009889), sotatercept reduced clinical worsening or death by 77% (HR 0.23, 95% CI 0.16\u20130.32,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and prolonged event-free survival by ~40\u2009weeks. World Health Organization (WHO) functional class improved in 40.3% vs 24.3% (RR 1.71, 95% CI 1.32\u20132.21), and 6-minute walk distance increased by MD 30.27\u2009m (95% CI 13.45\u201347.08), while pulmonary vascular resistance (PVR) declined significantly (MD \u2212247\u2009dyn\u00b7s\u00b7cm\u2013\n                      <jats:sup>5<\/jats:sup>\n                      , 95% CI \u2212301.7; \u2212192.2). Serious adverse events were slightly less frequent with sotatercept (26.2% vs 31.7%, RR 0.83); however, total bleeding (37.9% vs 18.7%, RR 2.00), epistaxis (26.7% vs 5.4%, RR 4.89), and telangiectasia (19.8% vs 6.4%, RR 3.24) were more common. TSA revealed conclusiveness in clinical worsening, WHO functional class, and PVR, as well as increases in bleeding events and epistaxis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Sotatercept significantly improves clinical outcomes and extends event-free survival in PAH, with an acceptable safety profile; however, caution is warranted regarding bleeding events. These results support its role as an add-on therapy in PAH management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>PROSPERO ID: CRD420251166414.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17534666261459209","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:25:46Z","timestamp":1781785546000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical, hemodynamic, and safety outcomes of sotatercept in pulmonary arterial hypertension: a meta-analysis of randomized trials with time-to-event data"],"prefix":"10.1177","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3518-9703","authenticated-orcid":false,"given":"Mohamed","family":"R. Murad","sequence":"first","affiliation":[{"name":"Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA"},{"name":"Faculty of Medicine, Al-Azhar University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5122-8200","authenticated-orcid":false,"given":"Ameer","family":"Awashra","sequence":"additional","affiliation":[{"name":"Department of Medicine, An-Najah National University, Rafidia Street, P.O. Box 7, Nablus, West Bank P4110257, Palestine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"S. Elgendy","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Tanta University, Tanta, Gharbia, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Wahdan","family":"Kasem","sequence":"additional","affiliation":[{"name":"Medical Research Group of Egypt (MRGE), Negida Academy, Arlington, MA, USA"},{"name":"Faculty of Medicine, Al-Azhar University, Cairo, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8300-0262","authenticated-orcid":false,"given":"Abdalhakim","family":"Shubietah","sequence":"additional","affiliation":[{"name":"Department of Medicine, Advocate Illinois Masonic Medical Center, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Safi","sequence":"additional","affiliation":[{"name":"Department of Pulmonary and Critical Care Medicine, University of Toledo, Toledo, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00879-2022"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01323-2024"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024277"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2213558"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2415160"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2508170"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-024-02058-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/eci.14386"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26104851"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-024-00694-w"},{"key":"e_1_3_4_12_2","unstructured":"Higgins JPT Thomas J Chandler J et al. 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