Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial. The Boston-New Haven-Barcelona Portal Hypertension Study Group.
To assess the effectiveness of propranolol in the prevention of initial variceal hemorrhage, a double-blind, randomized trial was carried out in three centers. Patients with cirrhosis (78% alcoholic), hepatic venous pressure gradients greater than 12 mm Hg and endoscopically proven esophageal varices were randomly assigned to propranolol (51 patients) or placebo (51 patients). Of the 102 patients, 58% were Child's class A, 34% were Child's class B and 8% were Child's class C. Daily dosage was determined by the administration of progressively increasing doses of propranolol with the hepatic vein catheter in place to achieve a 25% decrease in hepatic venous pressure gradient, a decrease in hepatic venous pressure gradient to less than 12 mm Hg or a decrease in resting heart rate to less than 55 beats/min. During a mean follow-up period of 16.3 mo, 11 patients in the placebo group (22%) bled from esophageal varices compared with 2 in the propranolol group (4%) during a mean period of 17.1 mo (p less than 0.01). Three additional patients (6%) in the placebo group bled from portal hypertensive gastropathy compared with none in the propranolol group. Propranolol appeared effective in preventing bleeding from large varices. Eleven deaths (22%) occurred in the placebo group compared with eight deaths (16%) in the propranolol group (NS). The mean dose of propranolol was 132 mg/day, and the median dose was 80 mg/day. Using a compliance index (pill count, clinic attendance, alcohol and propranolol levels and alcohol history), 81% of the propranolol patients and 77% of the placebo patients were considered compliant. Complications severe enough to require cessation of therapy occurred in eight patients (16%) in the propranolol group and four in the placebo group (8%) (NS). We conclude that propranolol effectively prevents the first variceal hemorrhage in patients with alcoholic cirrhosis and large esophageal varices but does not improve survival.
Conn
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Medical Service, West Haven Veterans Administration Medical Center, Yale University School of Medicine, Connecticut 06516.
Grace
N D
ND
Bosch
J
J
Groszmann
R J
RJ
Rodés
J
J
Wright
S C
SC
Matloff
D S
DS
Garcia-Tsao
G
G
Fisher
R L
RL
Navasa
M
M
D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004932:Esophageal and Gastric Varices / Q000150:complications*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006975:Hypertension, Portal / Q000150:complications; D008104:Liver Cirrhosis, Alcoholic / Q000150:complications; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*
D011433:Propranolol