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. 2019 May 27;11(5):464-476.
doi: 10.4254/wjh.v11.i5.464.

Carvedilol vs endoscopic variceal ligation for primary and secondary prevention of variceal bleeding: Systematic review and meta-analysis

Michael Dwinata  1 , David Dwi Putera  2 , Muhamad Fajri Adda'i  3 , Putra Nur Hidayat  4 , Irsan Hasan  4
Affiliations

Carvedilol vs endoscopic variceal ligation for primary and secondary prevention of variceal bleeding: Systematic review and meta-analysis

Michael Dwinata et al. World J Hepatol. .

Abstract

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 bleeding-related 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.

Keywords: Carvedilol; Liver cirrhosis; Portal hypertension; Prophylaxis; Variceal hemorrhage.

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Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest.

Figures

Figure 1
Figure 1
The results of the literature search process used in the current study, depicted using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram.
Figure 2
Figure 2
A risk of bias graph showing the researchers’ opinions on each risk of bias item (presented as percentages across all the seven included studies).
Figure 3
Figure 3
A risk of bias summary showing the researchers’ opinions on each risk of bias item for each of the seven included studies.
Figure 4
Figure 4
Meta-analysis forest plot of primary outcomes in primary prevention studies. A: Variceal bleeding; B: All-cause mortality; C: Bleeding-related mortality.
Figure 5
Figure 5
Meta-analysis forest plot of secondary outcomes in primary prevention studies. A: Side-effects of treatment; B: Compliance.
Figure 6
Figure 6
Meta-analysis forest plot of primary outcomes in secondary prevention studies. A: Variceal rebleeding; B: All-cause mortality.
See this image and copyright information in PMC

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