Drugs plus ligation to prevent rebleeding in cirrhosis: an updated systematic review

Liver Int. 2014 Jul;34(6):823-33. doi: 10.1111/liv.12452. Epub 2014 Jan 24.


Background & aims: Combined therapy with endoscopic variceal ligation (EVL) and β-blockers ± isosorbide mononitrate (ISMN) is currently recommended to prevent variceal rebleeding. However, the role of this combined therapy has been challenged by some studies. We performed a systematic review to assess the value of combined therapy with EVL and β-blockers ± ISMN as compared with each treatment alone to prevent rebleeding.

Methods: Databases, references and meeting abstracts were searched to retrieve randomized trials comparing combined therapy with EVL and β-blockers ± ISMN vs either treatment alone, to prevent variceal rebleeding in cirrhosis. Random-effects model was used for meta-analysis.

Results: We identified five studies comparing EVL alone or combined with drugs, including a total of 476 patients. Combination therapy reduced overall rebleeding [risk ratios (RR) = 0.44, 95% confidence interval (CI) = 0.28-0.69], and showed a trend towards lower mortality (RR = 0.58, 95% CI = 0.33-1.03), without increasing complications. We identified four trials comparing drugs alone or associated with EVL, including 409 patients. All used β-blockers plus ISMN. Variceal rebleeding decreased with combined therapy (P < 0.01) but rebleeding from oesophageal ulcers increased (P = 0.01). Overall, there was a trend towards lower rebleeding (RR = 0.76, 95% CI = 0.58-1.00) without effect on mortality (RR = 1.24, 95% CI = 0.90-1.70).

Conclusions: The addition of drug therapy to EVL improves the efficacy of EVL alone. However, the addition of EVL to β-blockers and ISMN achieves a non-significant decrease of rebleeding with no effect on mortality. Although combination therapy with EVL plus β-blockers ± ISMN is adequate to prevent rebleeding, β-blockers + ISMN alone may be a valid alternative.

Keywords: combined therapy; meta-analysis; variceal ligation; variceal rebleeding; β-blockers.

Publication types

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

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Animals
  • Chi-Square Distribution
  • Combined Modality Therapy
  • Drug Therapy, Combination
  • Endoscopy, Gastrointestinal
  • Esophageal and Gastric Varices / diagnosis
  • Esophageal and Gastric Varices / etiology
  • Esophageal and Gastric Varices / mortality
  • Esophageal and Gastric Varices / therapy*
  • Gastrointestinal Hemorrhage / diagnosis
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Hemorrhage / mortality
  • Gastrointestinal Hemorrhage / prevention & control*
  • Hemostatic Techniques* / adverse effects
  • Hemostatic Techniques* / mortality
  • Hemostatics / adverse effects
  • Hemostatics / therapeutic use*
  • Humans
  • Isosorbide Dinitrate / analogs & derivatives
  • Isosorbide Dinitrate / therapeutic use
  • Ligation
  • Liver Cirrhosis / complications*
  • Liver Cirrhosis / mortality
  • Odds Ratio
  • Recurrence
  • Risk Factors
  • Treatment Outcome


  • Adrenergic beta-Antagonists
  • Hemostatics
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate