Non‐Selective Beta‐Blocker Use Is Associated With Lower Mortality After Decompensation in Cirrhosis: A Nationwide Target Trial Emulation

BACKGROUND AND AIMS: Non-selective beta blockers (NSBBs) are well established for the prevention of variceal bleeding; however, their potential roles beyond this indication remain a matter of debate. We investigated the clinical outcomes of beta-blocker use in patients with cirrhosis after hospitalisation for cirrhotic complications, excluding variceal bleeding. METHODS: Using the Korean National Health Insurance Service database, we conducted an emulated target trial among 7725 patients with viral hepatitis-related cirrhosis hospitalised for hepatic encephalopathy, hepatorenal syndrome, ascites, and/or spontaneous bacterial peritonitis (2013-2023), comparing beta-blocker users (n = 2455) and non-users (n = 5270). The primary outcome was all-cause death within 6 months; the secondary outcome was rehospitalisation within 3 months. RESULTS: Compared to beta-blocker non-users, those receiving beta-blocker therapy had a lower risk of all-cause death within 6 months [cumulative incidence of mortality 7.8% in beta-blocker users vs. 11.0% in non-users; adjusted hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.68-0.97]. A lower risk of all-cause death associated with beta-blocker use was observed across complication types and patient subgroups. When analysed by dose and agent, each compared with non-use, an association with lower mortality was observed for low-dose beta blockers (HR 0.75, 95% CI 0.59-0.94) and for carvedilol (HR 0.55, 95% CI 0.32-0.94), whereas associations for moderate-to-high-dose therapy (HR 0.90, 95% CI 0.71-1.15) and propranolol (HR 0.87, 95% CI 0.72-1.04) were not statistically significant. CONCLUSIONS: Non-selective beta blockers were associated with reduced mortality and a modest reduction in all-cause readmission among patients with viral hepatitis-related cirrhosis after non-bleeding decompensating events (ClinicalTrials.gov: NCT06977685).