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Combination Endoscopic and Drug Therapy to Prevent Variceal Rebleeding in Cirrhosis


Background: Combining endoscopic therapy and β-blockers may improve outcomes in patients with cirrhosis and bleeding esophageal varices.

Purpose: To assess whether a combination of endoscopic and drug therapy prevents overall and variceal rebleeding and improves survival better than either therapy alone.

Data Sources: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and conference proceedings through 30 December 2007.

Study Selection: Randomized trials comparing endoscopic plus β-blocker therapy with either therapy alone, without language restrictions.

Data Extraction: Two reviewers independently extracted data on interventions and the primary study outcomes of overall rebleeding and mortality. Metaregression and stratified analysis were used to explore heterogeneity.

Data Synthesis: 23 trials (1860 patients) met inclusion criteria. Combination therapy reduced overall rebleeding more than endoscopic therapy alone (pooled relative risk, 0.68 [95% CI, 0.52 to 0.89]; I2 = 61%) or β-blocker therapy alone (pooled relative risk, 0.71 [CI, 0.59 to 0.86]; I2 = 0%). Combination therapy also reduced variceal rebleeding and variceal recurrence. Reduction in mortality from combination therapy did not statistically significantly differ from that from endoscopic (Peto odds ratio, 0.78 [CI, 0.58 to 1.07) or drug therapy (Peto odds ratio, 0.70 [CI, 0.46 to 1.06]). Effects were independent of the endoscopic procedure (injection sclerotherapy or banding). No trial-level variable associated with the effect was identified through metaregression or stratified analysis.

Limitation: Statistically significant heterogeneity in trial quality and evidence for selective reporting and publication bias were found.

Conclusion: A combination of endoscopic and drug therapy reduces overall and variceal rebleeding in cirrhosis more than either therapy alone

Annals of Internal Medicine, 15 July 2008 | Volume 149 Issue 2 | Pages 109-122