Published online May 27, 2019. doi: 10.4254/wjh.v11.i5.464
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
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.
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.
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
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.
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.
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.
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.