Meta-analysis: Combination endoscopic and drug therapy to prevent variceal rebleeding in cirrhosis

Ann Intern Med. 2008 Jul 15;149(2):109-22. doi: 10.7326/0003-4819-149-2-200807150-00007.


Background: Combining endoscopic therapy and beta-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 beta-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]; I(2) = 61%) or beta-blocker therapy alone (pooled relative risk, 0.71 [CI, 0.59 to 0.86]; I(2) = 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use*
  • Combined Modality Therapy
  • Endoscopy, Digestive System / adverse effects
  • Endoscopy, Digestive System / methods*
  • Esophageal and Gastric Varices / complications*
  • Esophageal and Gastric Varices / mortality
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Hemorrhage / prevention & control*
  • Humans
  • Ligation / adverse effects
  • Liver Cirrhosis / complications*
  • Publication Bias
  • Randomized Controlled Trials as Topic / standards
  • Sclerotherapy / adverse effects
  • Secondary Prevention


  • Adrenergic beta-Antagonists