title: Meta-analysis: isosorbide-mononitrate alone or with either beta-blockers or endoscopic therapy for the management of oesophageal varices.
abstract: BACKGROUND
  The evidence concerning the use of isosorbide-mononitrate (IsMn) for oesophageal varices is equivocal.
  
  
  OBJECTIVE
  To assess the effects of IsMn for patients with oesophageal varices and no previous bleeding (primary prevention) or previous variceal bleeding (secondary prevention).
  
  
  METHODS
  Systematic review with meta-analyses of randomized trials on IsMn alone or with beta-blockers or endoscopic therapy for oesophageal varices. Electronic and manual searches were combined. Randomized trials on primary and secondary prevention were included. The primary outcome measure was mortality. Intention-to-treat random effects meta-analyses were performed. The robustness of the results was assessed in trial sequential analyses.
  
  
  RESULTS
  Ten randomized trials on primary and 17 on secondary prevention were included. Evidence of bias was identified. No apparent effect of IsMn on mortality compared with placebo or beta-blockers or IsMn plus beta-blockers vs. beta-blockers was identified. Compared with endoscopic therapy, IsMn plus beta-blockers had no apparent effect on bleeding, but did seem to reduce mortality in secondary prevention (RR 0.73, 95% CI 0.59-0.89), but not in primary prevention. The effect of IsMn plus beta-blockers on mortality in secondary prevention was not confirmed in trial sequential analysis.
  
  
  CONCLUSIONS
  Isosorbide-mononitrate used alone or in combination with beta blockers does not seem to offer any reduction in bleeding in the primary or secondary prevention of oesophageal varices. Compared with endoscopic therapy, there may be a survival advantage in using IsMn and beta-blockers, but additional large multicentre trials are needed to verify this finding.
authors.affiliation: Department of Internal Medicine, Copenhagen University Hospital, Gentofte, Denmark. liselottegluud@yahoo.dk
authors.forename: L L
authors.initials: LL
authors.lastname: Gluud
authors.forename: E
authors.initials: E
authors.lastname: Langholz
authors.forename: A
authors.initials: A
authors.lastname: Krag
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D004932:Esophageal and Gastric Varices / Q000188:drug therapy* / Q000601:surgery; D004945:Esophagoscopy / Q000379:methods*; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D013223:Statistics as Topic; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000627:therapeutic use*
chemical_list: D000319:Adrenergic beta-Antagonists; D014665:Vasodilator Agents; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate