627 Carvedilol vs. Endoscopic Variceal Ligation in Primary Prevention of First Variceal Hemorrhage Episode: A Systematic Review and Meta-Analysis

Abstract

INTRODUCTION: Either a non-selective beta blocker or endoscopic variceal ligation (EVL) is recommended for the primary prevention of a first variceal hemorrhage episode in patients with medium or large sized varices. Carvedilol has been used for this purpose because of its additional alpha-1 antagonist effect and fewer hemodynamic complications. However, data supporting this recommendation are based on two previous randomized controlled trials. More studies have been published since these trials to investigate the benefit of carvedilol. We wanted to compare carvedilol with EVL in patients with esophageal varices to prevent the first variceal hemorrhage episode and to reduce mortality. METHODS: We comprehensively searched the databases of MEDLINE and EMBASE from inception to May 2019. Included studies were randomized controlled trials that investigated the efficacy of carvedilol compared to EVL to prevent the first variceal bleeding and to reduce mortality. The first variceal bleeding episode was defined as melena and/or hematemesis with endoscopic evidence of bleeding stigmata or recent variceal hemorrhage. Data from each study were combined using the random-effects, generic inverse variance method of DerSimonian and Laird to calculate pooled risk ratio (RR) and 95% confidence intervals. RESULTS: Four randomized controlled trials from 2009 to 2018 involving 556 patients (276 patients in the carvedilol group and 280 patients in the EVL group) were included in this meta-analysis. The mean age was 50 years. Compared to EVL, carvedilol did not significantly decrease the first variceal bleeding incidence or 1-year mortality (pooled RR 1.11 (0.56-2.19), P = 0.767, I2 = 53% and 1.22 (0.78-1.91), P = 0.38, I2 = 0%, respectively) (Figures 1 and 2). Serious adverse events that were intolerable and required specific therapy leading to discontinuation of the treatment arm was reported in 4 studies and did not show any significant difference between the carvedilol group and the EVL group (pooled RR 1.14 (0.78-1.68), P = 0.49, I2 = 6.8%) (Figure 3). CONCLUSION: Our study demonstrated a non-significant difference between carvedilol and EVL to prevent first variceal bleeding or decrease mortality. There was no difference in serious side effects. More randomized controlled trials with larger sample sizes and long term follow up are required to better understand the potential benefit of carvedilol. Our analysis supports the benefit of carvedilol as primary prophylaxis of variceal hemorrhage in cirrhotic patients.