Carvedilol vs endoscopic variceal ligation for primary and secondary prevention of variceal bleeding: Systematic review and metaanalysis

BACKGROUND Variceal hemorrhage is associated with high mortality and is the cause of death for 20-30% of patients with cirrhosis. Nonselective β blockers (NSBBs) or endoscopic variceal ligation (EVL) are recommended for primary prevention of variceal bleeding in patients with medium to large esophageal varices. Meanwhile, combination of EVL and NSBBs is the recommended approach for the secondary prevention. Carvedilol has greater efficacy than other NSBBs as it decreases intrahepatic resistance. We hypothesized that there was no difference between carvedilol and EVL intervention for primary and secondary prevention of variceal bleeding in cirrhosis patients. AIM To evaluate the efficacy of carvedilol compared to EVL for primary and secondary prevention of variceal bleeding in cirrhotic patients METHODS We searched relevant literatures in major journal databases (CENTRAL, MEDLINE, and EMBASE) from March to August 2018. Patients with cirrhosis and portal hypertension, regardless of aetiology and severity, with or without a history of variceal bleeding, and aged ≥ 18 years old were included in this review. Only randomized controlled trials (RCTs) that compared the efficacy of carvedilol and that of EVL for primary and secondary prevention of variceal bleeding and mortality in patients with cirrhosis and portal hypertension were considered, irrespective of publication status, year of publication, and language. RESULTS Seven RCTs were included. In four trials assessing the primary prevention, no significant difference was found on the events of variceal bleeding (RR: 0.74, 95%CI: 0.37-1.49), all-cause mortality (RR: 1.10, 95%CI: 0.76-1.58), and bleedingrelated mortality (RR: 1.02, 95%CI: 0.34-3.10) in patients who were treated with carvedilol compared to EVL. In three trials assessing secondary prevention, there was no difference between two interventions for the incidence of rebleeding (RR: 1.10, 95%CI: 0.75-1.61). The fixed-effect model showed that, compared to EVL, carvedilol decreased all-cause mortality by 49% (RR: 0.51, 95%CI: 0.33-0.79), with little or no evidence of heterogeneity. CONCLUSION Carvedilol had similar efficacy to EVL in preventing the first variceal bleeding in cirrhosis patients with esophageal varices. It was superior to EVL alone for secondary prevention of variceal bleeding in regard to all-cause mortality reduction.