title: Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.
abstract: BACKGROUND
  Nonselective beta-adrenergic blockers decrease portal pressure and prevent variceal hemorrhage. Their effectiveness in preventing varices is unknown.
  
  
  METHODS
  We randomly assigned 213 patients with cirrhosis and portal hypertension (minimal hepatic venous pressure gradient [HVPG] of 6 mm Hg) to receive timolol, a nonselective beta-blocker (108 patients), or placebo (105 patients). The primary end point was the development of gastroesophageal varices or variceal hemorrhage. Endoscopy and HVPG measurements were repeated yearly.
  
  
  RESULTS
  During a median follow-up of 54.9 months, the rate of the primary end point did not differ significantly between the timolol group and the placebo group (39 percent and 40 percent, respectively; P=0.89), nor were there significant differences in the rates of ascites, encephalopathy, liver transplantation, or death. Serious adverse events were more common among patients in the timolol group than among those in the placebo group (18 percent vs. 6 percent, P=0.006). Varices developed less frequently among patients with a baseline HVPG of less than 10 mm Hg and among those in whom the HVPG decreased by more than 10 percent at one year and more frequently among those in whom the HVPG increased by more than 10 percent at one year.
  
  
  CONCLUSIONS
  Nonselective beta-blockers are ineffective in preventing varices in unselected patients with cirrhosis and portal hypertension and are associated with an increased number of adverse events. (ClinicalTrials.gov number, NCT00006398.)
authors.affiliation: Yale University School of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA.
authors.forename: Roberto J
authors.initials: RJ
authors.lastname: Groszmann
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Garcia-Tsao
authors.forename: Jaime
authors.initials: J
authors.lastname: Bosch
authors.forename: Norman D
authors.initials: ND
authors.lastname: Grace
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Burroughs
authors.forename: Ramon
authors.initials: R
authors.lastname: Planas
authors.forename: Angels
authors.initials: A
authors.lastname: Escorsell
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Garcia-Pagan
authors.forename: David
authors.initials: D
authors.lastname: Patch
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Matloff
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Robert
authors.initials: R
authors.lastname: Makuch
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D004311:Double-Blind Method; D004932:Esophageal and Gastric Varices / Q000209:etiology / Q000517:prevention & control*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D013999:Timolol / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure
chemical_list: D000319:Adrenergic beta-Antagonists; D013999:Timolol