title: Drugs plus ligation to prevent rebleeding in cirrhosis: an updated systematic review.
abstract: OBJECTIVE
  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.
authors.affiliation: Gastrointestinal Bleeding Unit, Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Autonomous University, Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Puente
authors.forename: Virginia
authors.initials: V
authors.lastname: Hernández-Gea
authors.forename: Isabel
authors.initials: I
authors.lastname: Graupera
authors.forename: Marta
authors.initials: M
authors.lastname: Roque
authors.forename: Alan
authors.initials: A
authors.lastname: Colomo
authors.forename: Maria
authors.initials: M
authors.lastname: Poca
authors.forename: Carles
authors.initials: C
authors.lastname: Aracil
authors.forename: Ignasi
authors.initials: I
authors.lastname: Gich
authors.forename: Carlos
authors.initials: C
authors.lastname: Guarner
authors.forename: Càndid
authors.initials: C
authors.lastname: Villanueva
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000818:Animals; D016009:Chi-Square Distribution; D003131:Combined Modality Therapy; D004359:Drug Therapy, Combination; D016099:Endoscopy, Gastrointestinal; D004932:Esophageal and Gastric Varices / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D006471:Gastrointestinal Hemorrhage / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006489:Hemostatic Techniques / Q000009:adverse effects / Q000401:mortality; D006490:Hemostatics / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives / Q000627:therapeutic use; D008026:Ligation; D008103:Liver Cirrhosis / Q000150:complications* / Q000401:mortality; D016017:Odds Ratio; D012008:Recurrence; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D006490:Hemostatics; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate
keywords: combined therapy; meta-analysis; variceal ligation; variceal rebleeding; β-blockers