Carvedilol Versus Other Nonselective Beta Blockers for Variceal Bleeding Prophylaxis and Death: A Network Meta-analysis

BACKGROUND AND AIMS: We aimed to perform a network meta-analysis (NWM) to examine comparative effectiveness of non-selective beta blockers (NSBBs) on prophylaxis of gastroesophageal variceal bleeding (GVB) and mortality benefit. METHODS: MEDLINE (OVID) and EMBASE databases were searched for eligible randomized clinical trials (RCTs) from inception to July 3, 2021. Outcomes of interest included primary/secondary prophylaxis of GVB, failure to achieve hepatic venous pressure gradient (HVPG) decremental response, liver-related and all-cause mortality. A Bayesian NWM was performed to derive relative risk (RR) with 95% credible intervals (CrIs). The ranking probability of each NSBB was assessed by surface under cumulative ranking curve (SUCRA). RESULTS: Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were included. Compared with placebo, nadolol ranked first for reducing variceal bleeding [RR:0.25, (95% CrI:0.11–0.51); SUCRA:0.898], followed by carvedilol [RR:0.33, (95% CrI: 0.11–0.88); SUCRA:0.692] and propranolol [RR:0.52, (95% CrI:0.37–0.75); SUCRA:0.405]. Carvedilol was more effective than propranolol in achieving HVPG decremental response [RR:0.43, (95% CrI: 0.26–0.69)]. Carvedilol ranked first for reducing all-cause mortality [RR: 0.32, (95% CrI:0.17–0.57); SUCRA:0.963), followed by nadolol [RR:0.48, (95% CI:0.29–0.77); SUCRA:0.688], and propranolol [RR:0.77, (95% CI:0.58–1.02); SUCRA: 0.337]. Similar findings were observed for liver-related mortality. Carvedilol ranked the safest. The RR of adverse events was 4.38, (95% CrI:0.33–161.4); SUCRA:0.530, followed by propranolol [RR: 7.54, (95% CrI:1.90–47.89); SUCRA:0.360], and nadolol [RR: 18.24, (95% CrI:91.51–390.90); SUCRA:0.158]. CONCLUSIONS: Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices.