Carvedilol versus Propranolol in Patients with Hepatocellular Carcinoma: A Nationwide Cohort Study

Introduction: Beta-blockers reduce portal hypertension, however, evidence comparing carvedilol and propranolol in patients with hepatocellular carcinoma (HCC) is lacking. We aimed to compare the clinical outcomes of carvedilol versus propranolol in patients with HCC. Methods: Using the Korean National Health Insurance Service database (2009-2023), we identified 11,124 patients with newly diagnosed HCC who were prescribed either carvedilol (n=2,457) or propranolol (n=8,667) within 180 days of diagnosis. The primary outcome was all-cause mortality, and the secondary outcome was hepatic decompensation. Multivariable Cox regression and 1:2 PS matching were used as primary analytical approaches, with sensitivity analyses restricted to 6-month survivors and a new-user design. Results: During a median follow-up of 1.5 years, carvedilol use was associated with a significantly lower risk of hepatic decompensation (adjusted hazard ratio (aHR) 0.67; 95% confidence interval (CI) 0.62–0.72) and all-cause mortality (aHR 0.84; 95% CI 0.79–0.90) compared to propranolol. In the 1:2 PS-matched cohort (n=5,922), these associations remained consistent for both decompensation (HR 0.68; 95% CI 0.63–0.74) and mortality (HR 0.84; 95% CI 0.78–0.90). These benefits were consistent across various subgroups, and in sensitivity analysis excluding early death within 6 months from diagnosis and using a new-user design. Conclusion: In patients with HCC, carvedilol was associated with better survival and lower risk of hepatic decompensation than propranolol. Carvedilol may be the preferred beta-blocker over propranolol in the setting of HCC.