{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T02:17:22Z","timestamp":1781921842950,"version":"3.54.5"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      Endothelin A (ET\n                      <jats:sub>A<\/jats:sub>\n                      ) receptor antagonists may reduce cirrhosis\u2010associated portal hypertension (PH). They are associated with fluid retention, which might be mitigated by sodium\u2013glucose co\u2010transporter 2 inhibitors (SGLT2is). Efficacy, safety and tolerability of combining the selective ET\n                      <jats:sub>A<\/jats:sub>\n                      receptor antagonist zibotentan and the selective SGLT2i dapagliflozin were investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients with compensated cirrhosis (Child\u2010Pugh A) were randomized 1:1 to zibotentan 2.5\u00a0mg plus dapagliflozin 10\u00a0mg (zibo\/dapa) or placebo in a 6\u2010week parallel, double\u2010blind Phase II study. The absolute change in hepatic venous pressure gradient (HVPG) from baseline to week 6 was evaluated in the full analysis set using analysis of covariance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 28 participants (n\u2009=\u200914 per group), median age was 64\u2009years (range: 37\u201378), common causes of cirrhosis were metabolic dysfunction\u2010associated steatotic (46%) or alcohol\u2010associated liver disease (39%), and 46% were receiving stable doses of non\u2010selective beta\u2010blockers. Baseline HVPG was 6.5\u201319\u2009mmHg, and 16\/28 had clinically significant portal hypertension. Absolute change in HVPG at week 6 was not different between groups (1.02\u2009mmHg [90% CI\u2009\u22120.31, 2.35]). There was a trend towards decreased HVPG in patients with baseline HVPG \u226512\u2009mmHg receiving zibo\/dapa. Systolic and diastolic blood pressure were also reduced by zibo\/dapa\n                      <jats:italic>vs<\/jats:italic>\n                      . placebo. Three mild adverse events (peripheral oedema) were reported (zibotentan\/dapagliflozin, n\u2009=\u20092; placebo, n\u2009=\u20091). No serious adverse events or drug\u2010induced liver injuries were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combined zibo\/dapa was well tolerated and had a good safety profile in patients with compensated cirrhosis, but had no conclusive effect on HVPG.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/bcp.70332","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T06:29:51Z","timestamp":1765261791000},"page":"1326-1338","source":"Crossref","is-referenced-by-count":1,"title":["Effects of zibotentan and dapagliflozin combined in patients with compensated cirrhosis: A randomized placebo\u2010controlled exploratory study"],"prefix":"10.1002","volume":"92","author":[{"given":"Juan Carlos","family":"Garcia\u2010Pagan","sequence":"first","affiliation":[{"name":"Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Cl\u00ednic, Institut de Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS). CIBEREHD (Centro de Investigaci\u00f3n Biom\u00e9dica en Red Enfermedades Hep\u00e1ticas y Digestivas). Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN RARE\u2010Liver). Departament de Medicina i Ci\u00e8ncies de la Salut. Universitat de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise Lotte","family":"Gluud","sequence":"additional","affiliation":[{"name":"Gastro Unit Copenhagen University Hospital Hvidovre and Department of Clinical Medicine, University of Copenhagen  Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias","family":"Mandorfer","sequence":"additional","affiliation":[{"name":"Vienna Hepatic Hemodynamic Lab, Division of Gastroenterology and Hepatology, Department of Medicine III Medical University of Vienna  Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f6rn M.","family":"Schattenberg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II Saarland University Medical Center  Homburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"De Gottardi","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology, Luzerner Kantonsspital, Luzern  Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Berzigotti","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital University of Bern  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Ignacio","family":"Fortea","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Clinical and Translational Research in Digestive Diseases, Valdecilla Research Institute (IDIVAL) Marqu\u00e9s de Valdecilla University Hospital  Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agustin Albillos","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Dept of Gastroenterology, Hospital Universitario Ramon y Cajal, IRYCIS, CIBEREHD University of Alcala  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edilmar","family":"Alvarado\u2010Tapias","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Hospital Santa Creu i Sant Pau, Barcelona, Spain. Centre for Biomedical Research in Liver and Digestive Diseases Network (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain. Universitat Aut\u00f2noma de Barcelona (UAB), Departament de Medicina UAB  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Berning","sequence":"additional","affiliation":[{"name":"Department of Medicine I University Hospital Dresden, Technische Universit\u00e4t Dresden (TU Dresden)  Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Petryszyn","sequence":"additional","affiliation":[{"name":"Late\u2010stage Clinical Development, Cardiovascular, Renal and Metabolic, AstraZeneca  Warsaw Poland"},{"name":"Department of Clinical Pharmacology Wroclaw Medical University  Wroclaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia","family":"Henricson","sequence":"additional","affiliation":[{"name":"Biopharmaceutical Clinical Operations, Cardiovascular, Renal and Metabolic, AstraZeneca  Gothenburg 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