Meta-Analysis
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 27, 2019; 11(5): 464-476
Published online May 27, 2019. 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, David Dwi Putera, Muhamad Fajri Adda’i, Putra Nur Hidayat, Irsan Hasan
Michael Dwinata, Department of Internal Medicine, Depati Hamzah General Hospital, Pangkalpinang 33684, Indonesia
David Dwi Putera, School of Medicine and Public Health, University of Sydney, Sydney 2006, Australia
Muhamad Fajri Adda’i, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
Putra Nur Hidayat, Irsan Hasan, Hepatobiliary Division, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Cipto Mangunkusumo National General Hospital, Jakarta 10430, Indonesia
Author contributions: Dwinata M proposed the study; Dwinata M and Putera DD performed the literature search and wrote the research draft; Dwinata M and Putera DD collected and synthesized the data; Dwinata M, Putera DD, Hidayat PN, and Adda’i MF performed the data interpretation; Hasan I reviewed the manuscript and acted as an advisor.
Conflict-of-interest statement: No potential conflicts of interest.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Michael Dwinata, MD, Staff Physician, Department of Internal Medicine, Depati Hamzah General Hospital, Soekarno Hatta Street, Pangkalpinang 33684, Indonesia. mdwinata@gmail.com
Telephone: +62-822-99066500
Received: March 4, 2019
Peer-review started: March 5, 2019
First decision: March 25, 2019
Revised: April 8, 2019
Accepted: April 26, 2019
Article in press: April 28, 2019
Published online: May 27, 2019
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, Variceal hemorrhage, Portal hypertension, Prophylaxis

Core tip: This study was an updated meta-analysis of primary prevention and the first meta-analysis of secondary prevention of variceal bleeding in cirrhotic patients. Seven relevant randomized controlled trials were included. Based on the pooled analysis, carvedilol had similar efficacy to endoscopic variceal ligation (EVL) in preventing the first variceal hemorrhage in cirrhosis patients with esophageal varices. Carvedilol was superior to EVL for secondary prevention of variceal bleeding in regard to all-cause mortality reduction by 49% (RR: 0.51, 95%CI: 0.33–0.79).