Propranolol in the prevention of the first hemorrhage from esophagogastric varices: A multicenter, randomized clinical trial

Abstract

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.

Transjugular Intrahepatic Portal-systemic Shunts: The State of the Art

“…Using 8-mm and 10-mm stents, which creates shunts with diameters of approximately 7 mm and 9 mm, respectively, it has been possible to maintain a mild degree of portal hypertension without HE. We, too, have noted that partial reduction of elevated portal venous pressure induced by propranolol is sufficient to prevent variceal bleeding (34).…”

Current use of transjugular intrahepatic portosystemic shunts

“…Predictors of hemorrhage include persistent use of alcohol, poor liver function, large varices, endoscopic red signs, and high hepatic venous pressure gradient [7,9]. Therapy with beta-blockers is the standard prophylaxis for bleeding [10,11]. Once acute bleeding commences, endoscopic ligation of the esophageal varices, in combination with medications that reduce splanchnic blood flow, is successful in up to 90% of patients [12,13].…”

Preventing First Variceal Hemorrhage in Cirrhosis

“…8 Table 1 shows the cumulative analysis of those trials reporting the effect of BB in preventing the growth of esophageal varices and decreasing the bleeding risk. [29][30][31][32] When the results of the 4 trials addressing this issue were pooled, the bleeding rate was 25 out of 228 patients treated with placebo (10.9%) and 15 out of 226 patients treated with BB (6.6%) (absolute risk difference 4.6%; 95% CI, À 9.7% to À 0.5%). These data suggest a trend in favor of BB to reduce the risk of bleeding in patients with small varices.…”