The Comparative Effectiveness of Carvedilol Versus Other Nonselective β-Blockers in Cirrhosis

BACKGROUND: In cirrhosis, nonselective β-blockers (NSBBs; carvedilol, nadolol, and propranolol) reduce hepatic portal pressure and have demonstrated benefit versus placebo for preventing decompensation. Although carvedilol has emerged as the preferred NSBB, direct evidence remains limited about its effectiveness for preventing decompensation and death versus other NSBBs. OBJECTIVE: To compare the effectiveness of carvedilol versus nadolol versus propranolol in cirrhosis. DESIGN: Database cohort study. SETTING: A U.S. administrative claims database, Optum Clinformatics Data Mart (2013 to 2025). PARTICIPANTS: Adults with cirrhosis initiating carvedilol, nadolol, or propranolol. MEASUREMENTS: The primary outcome was a composite of hospitalization for major decompensation (ascites, spontaneous bacterial peritonitis SBP, hepatorenal syndrome HRS, hepatic encephalopathy, or variceal hemorrhage). Absolute risk differences (RDs) and risk ratios (RRs) at 6 months of follow-up were estimated using inverse probability of treatment weighting accounting for 129 preexposure covariates. RESULTS: Carvedilol initiators had meaningfully lower 6-month risk for major decompensation events compared with nadolol (RD, -3.69 percentage points 95% CI, -5.33 to -2.09 percentage points; RR, 0.80 CI, 0.72 to 0.88) or propranolol (RD, -2.88 percentage points CI, -4.29 to -1.49 percentage points; RR, 0.83 CI, 0.76 to 0.90). This included substantially lower 6-month risk for specific decompensation events with carvedilol compared with nadolol or propranolol, including reduced risk for variceal hemorrhage (RDs, -3.51 percentage points CI, -4.79 to -2.20 percentage points and -1.65 percentage points CI, -2.71 to -0.59 percentage points, respectively) and ascites, SBP, or HRS (RDs, -3.05 percentage points CI, -4.52 to -1.75 percentage points and -1.58 percentage points CI, -2.77 to -0.44 percentage points, respectively). LIMITATION: Nonrandomized treatment selection. CONCLUSION: Among U.S. patients with cirrhosis, carvedilol initiation-as opposed to nadolol or propranolol-was associated with meaningfully lower rates of major decompensation events. PRIMARY FUNDING SOURCE: National Institutes of Health.