title: Propranolol for prophylaxis of bleeding in cirrhotic patients with large varices: a multicenter, randomized clinical trial. The Italian Multicenter Project for Propranolol in Prevention of Bleeding.
abstract: To assess if propranolol prevents the first bleeding in cirrhosis, we randomly assigned 174 patients with large varices to either propranolol in doses reducing the resting heart rate by 25% (85 patients) or to a placebo (oral vitamin K, 89 patients). Sixty-nine patients had alcoholic cirrhosis, 24 posthepatitis cirrhosis and 81 cryptogenic cirrhosis. At the time of inclusion, 75 patients (43%) had ascites and according to the Child-Pugh classification, 103 (59%) had Class A disease, 60 (34%) Class B and 11 (7%) Class C. We report here an interim analysis of the study when all patients had been followed for at least 1 year (mean follow-up = 22 months). At this time, the cumulative proportion of patients free of bleeding was 74% (both differences not significant), respectively. A retrospective analysis showed that the cumulative percentage of patients free of bleeding was significantly higher in the propranolol- than in the control-group in the subsets of patients without ascites or in Child-Pugh Class A: respectively, 87 vs. 64% (p = 0.023) and 88 vs. 64% (p = 0.01). No differences in bleeding incidence were found in patients with ascites or in Child-Pugh Class B or C. Propranolol treatment did not affect survival in any subgroup. Twenty-five patients had to be withdrawn from propranolol because of side effects (n = 23) or low compliance (n = 2). If confirmed on a longer follow-up, these results suggest that propranolol could prevent the first bleeding in patients with well-compensated cirrhosis.
mesh_terms: D002986:Clinical Trials as Topic; D004932:Esophageal and Gastric Varices / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use*; D011897:Random Allocation; D012189:Retrospective Studies; D013997:Time Factors; D014812:Vitamin K / Q000627:therapeutic use
chemical_list: D014812:Vitamin K; D011433:Propranolol