{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:33:37Z","timestamp":1771047217760,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014468","name":"Mallinckrodt Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014468","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Terlipressin is the FDA\u2010approved systemic vasoconstrictor therapy for hepatorenal syndrome\u2010acute kidney injury (HRS\u2010AKI)\u2014a rapidly progressive renal failure occurring in patients with decompensated cirrhosis and ascites. Bradycardia, a known effect of terlipressin, as well as other arrhythmias, has previously been reported in terlipressin\u2010treated patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To assess terlipressin\u2010related cardiac adverse events (AEs) in patients with HRS\u2010AKI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Three North American\u2010centric Phase III, randomised, placebo\u2010controlled studies (OT\u20100401, REVERSE, CONFIRM) were pooled in the largest\u2010to\u2010date prospective database. Cardiac AEs were reported by the investigators for each trial and retrospectively analysed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bradycardia was the only cardiac AE reported more frequently in terlipressin\u2010treated patients compared with placebo (6.3% [22\/349] vs. 0.8% [2\/249]). In the terlipressin group, no bradycardia AEs were serious, 4.5% (1\/22) of patients required a dose interruption, 9.1% (2\/22) required a dose reduction, and none discontinued treatment due to bradycardia. The incidences of other arrhythmia AEs were similar in both treatment groups (terlipressin: 7.4% [26\/349]; placebo 8.8% [22\/249]). The incidence of atrial fibrillation serious AEs (SAEs) was low (terlipressin: 0.9% [3\/349]; placebo: 1.6% [4\/249]). There were no AE reports of torsades de pointes, while a QT interval prolongation was reported in two patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In a pooled analysis, bradycardia was observed in 6% of terlipressin\u2010treated patients but rarely required a dose interruption or reduction. Arrhythmia SAE incidences were low and similar in both treatment groups. Routine intensive cardiac monitoring for the detection of arrhythmias may not be necessary during terlipressin administration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>OT\u20100401: NCT00089570, REVERSE: NCT01143246 and CONFIRM: NCT02770716<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apt.70297","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T09:48:31Z","timestamp":1753350511000},"page":"1192-1201","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bradycardia and Other Arrhythmias in Patients With Hepatorenal Syndrome\u2010Acute Kidney Injury Following Terlipressin Treatment: A Pooled Analysis of Three North American Phase\n                    <scp>III<\/scp>\n                    Clinical Studies"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4928-3681","authenticated-orcid":false,"given":"Jasmohan S.","family":"Bajaj","sequence":"first","affiliation":[{"name":"School of Internal Medicine Virginia Commonwealth University  Richmond Virginia USA"},{"name":"Richmond VA Medical Center  Richmond Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8234-4485","authenticated-orcid":false,"given":"Paul","family":"Kwo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine Stanford University  Palo Alto California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7677-6628","authenticated-orcid":false,"given":"Stephen Chris","family":"Pappas","sequence":"additional","affiliation":[{"name":"Orphan Therapeutics, LLC  Longboat Key Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3640-4851","authenticated-orcid":false,"given":"Jacqueline G.","family":"O'Leary","sequence":"additional","affiliation":[{"name":"Dallas VA Medical Center  Dallas Texas USA"},{"name":"Baylor University Medical Center  Dallas Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9155-3513","authenticated-orcid":false,"given":"Khurram","family":"Jamil","sequence":"additional","affiliation":[{"name":"Mallinckrodt Pharmaceuticals  Bridgewater New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanaz","family":"Cardoza","sequence":"additional","affiliation":[{"name":"Mallinckrodt Pharmaceuticals  Bridgewater New Jersey 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