Carvedilol and nonselective-beta-blockers vs endoscopic ligation for prophylaxis of esophageal variceal hemorrhage in cirrhosis: Systematic review and meta-analysis

Abstract

BACKGROUND Variceal hemorrhage remains a major contributor to morbidity and mortality among patients with liver cirrhosis. Although primary prophylaxis is strongly recommended, uncertainty persists regarding the relative efficacy of carvedilol and other nonselective beta-blockers (NSBBs) vs endoscopic variceal ligation (EVL). AIM To compare the efficacy of carvedilol and other NSBBs with EVL for the primary prophylaxis of variceal bleeding in patients with cirrhosis. METHODS A systematic search of PubMed, Cochrane Library, EMBASE, and ScienceDirect (August 2025) was conducted to identify randomized controlled trials and prospective cohorts comparing carvedilol or other NSBBs with EVL. Data were pooled using a random-effects meta-analysis, and relative risk (RR) was used as the summary measure. The primary outcome was first variceal bleeding, while the secondary outcome was bleeding-related mortality. RESULTS Five studies (n = 752) were included, involving 380 patients receiving carvedilol/NSBBs and 372 patients undergoing EVL. Carvedilol significantly reduced the risk of first variceal bleeding compared with EVL (RR = 0.64, 95% confidence interval [CI]: 0.44-0.94; P = 0.02, I 2 = 11%). The absolute bleeding rates were 9.7% with carvedilol vs 15.1% with EVL. Bleed-related mortality did not differ significantly (RR = 0.76, 95%CI: 0.37-1.58; P = 0.47, I 2 = 4%), although the event numbers were low. Adverse events differed by modality, with carvedilol predominantly associated with systemic intolerance, whereas EVL caused procedure-related complications. CONCLUSION Carvedilol and other NSBBs were associated with a lower risk of first variceal bleeding compared with EVL when used as primary prophylaxis in patients with cirrhosis.

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