Bradycardia and Other Arrhythmias in Patients With Hepatorenal Syndrome‐Acute Kidney Injury Following Terlipressin Treatment: A Pooled Analysis of Three North American Phase III Clinical Studies

作者：Jasmohan S. Bajaj, Paul Y. Kwo, S. Chris Pappas, Jacqueline O'leary, Khurram Jamil, Sanaz Cardoza, Florence Wong · 发表于：Alimentary Pharmacology & Therapeutics · 年份：2025 · DOI：10.1111/apt.70297 · 被引用次数：3 · 研究领域：Liver Disease and Transplantation、Drug-Induced Hepatotoxicity and Protection、Electrolyte and hormonal disorders

BACKGROUND: Terlipressin is the FDA-approved systemic vasoconstrictor therapy for hepatorenal syndrome-acute kidney injury (HRS-AKI)-a 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-treated patients. AIM: To assess terlipressin-related cardiac adverse events (AEs) in patients with HRS-AKI. METHODS: Three North American-centric Phase III, randomised, placebo-controlled studies (OT-0401, REVERSE, CONFIRM) were pooled in the largest-to-date prospective database. Cardiac AEs were reported by the investigators for each trial and retrospectively analysed. RESULTS: Bradycardia was the only cardiac AE reported more frequently in terlipressin-treated 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. CONCLUSIONS: In a pooled analysis, bradycardia wa...