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 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]. Conclu-sions: Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among pa-tients with gastroesophageal varices.

Automated summary

This study conducted a network meta-analysis to compare the effectiveness of non-selective beta blockers (NSBBs) in the prophylaxis of gastroesophageal variceal bleeding (GVB) and mortality benefit. The results showed that compared to placebo, nadolol ranked first in reducing variceal bleeding, followed by carvedilol and propranolol. Carvedilol was more effective in achieving HVPG decremental response and had the highest safety.