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:
Corresponding author: Michael Dwinata, MD, Staff Physician, Department of Internal Medicine, Depati Hamzah General Hospital, Soekarno Hatta Street, Pangkalpinang 33684, Indonesia.
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
Research background

Variceal hemorrhage is associated with high mortality and is the cause of death for 20%–30% of patients with cirrhosis. Either traditional nonselective β blockers (NSBBs) (i.e. propranolol or nadolol), carvedilol, or endoscopic variceal ligation (EVL) is 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.

Research motivation

Some of the major drawbacks of EVL are invasive, costly, and unavailable in many areas, especially in developing countries. A better understanding of the efficacy of carvedilol compared to EVL might provide less invasive and more accessible prevention strategy for variceal bleeding in cirrhosis patients.

Research objectives

We conducted this meta-analysis to evaluate the efficacy of carvedilol compared to EVL for primary and secondary prevention of variceal bleeding in cirrhotic patients with esophageal varices

Research methods

We searched relevant literatures in major journal databases (CENTRAL, MEDLINE, and EMBASE) from March to August 2018. 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.

Research results

Seven RCTs were included in this meta-analysis. For primary prevention strategy, we found no significant difference between carvedilol and EVL on the events of variceal bleeding, all-cause mortality, and bleeding-related mortality. For secondary prevention strategy, we found no difference between two interventions for the incidence of rebleeding. Interestingly, 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.

Research conclusions

Carvedilol had similar efficacy to EVL in preventing the first variceal bleeding in cirrhosis patients with esophageal varices. In clinical practice, the use of carvedilol or EVL for prevention of first variceal bleeding may depends on physicians’ and patients’ preference. For prevention of rebleeding, we considered that carvedilol was superior to EVL alone in regard to all-cause mortality reduction.

Research perspectives

This study demonstrated significant benefit of using carvedilol for secondary prevention of variceal bleeding in cirrhosis patients. We highly suggest that future clinical trials should compare between carvedilol and combination of EVL and traditional NSBBs (i.e., propranolol or nadolol) or carvedilol to enrich our understanding about efficacy of carvedilol for the prevention of esophageal varices rebleeding.