Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis.
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.)
Groszmann
Roberto J
RJ
Yale University School of Medicine, Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516, USA.
Garcia-Tsao
Guadalupe
G
Bosch
Jaime
J
Grace
Norman D
ND
Burroughs
Andrew K
AK
Planas
Ramon
R
Escorsell
Angels
A
Garcia-Pagan
Juan Carlos
JC
Patch
David
D
Matloff
Daniel S
DS
Gao
Hong
H
Makuch
Robert
R
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
D000319:Adrenergic beta-Antagonists; D013999:Timolol