A Randomized Controlled Study of Propranolol for Prevention of Recurrent Gastrointestinal Bleeding in Patients with Cirrhosis: A Final Report

TLDR

Previous trials demonstrated that continuous propranolol reduces recurrent gastrointestinal bleeding in cirrhosis patients, but follow‑up was limited to one year. This study evaluates whether extending propranolol therapy further improves its efficacy. Seventy‑four cirrhotic patients admitted for gastrointestinal bleeding were randomized to propranolol, titrated to a 25% resting heart‑rate reduction, or placebo and followed for at least two years. After two years, propranolol markedly lowered recurrent bleeding (87 % vs 42 % at 1 year, 79 % vs 32 % at 2 years) and improved survival (90 % vs 57 % at 2 years), confirming its benefit in this population.

Abstract

We have previously reported the results of a controlled trial showing that continuous oral administration of propranolol reduced the risk of recurrent gastrointestinal bleeding in patients with cirrhosis; only part of our patients had been followed for 1 year. This controlled trial was continued for an additional year; accordingly, all of our patients have now been followed for at least 2 years. The purpose of the present study is to determine whether prolonged administration enhances the efficacy of this therapy. Seventy-four patients with cirrhosis, admitted for an episode of gastrointestinal bleeding, were included in this study; ascites, jaundice and encephalopathy were absent or mild and transient. The patients were randomly assigned to two groups; one group of 38 patients received propranolol twice daily at doses that reduced the resting heart rate by 25%, the other group of 36 patients received a placebo twice daily. The cumulative percentages of patients free of recurrent gastrointestinal bleeding 1 and 2 years after inclusion were 87 and 79% in the propranolol group, and 42 and 32% in the placebo group; both differences were highly significant (p < 0.0001). Furthermore, the cumulative percentages of surviving patients 1 and 2 years after inclusion were 94 and 90% in the propranolol group, and 84 and 57% in the placebo group; the difference between the two groups was not significant at 1 year, but was statistically significant at 2 years (p < 0.02). We conclude that, in patients with cirrhosis in good condition, propranolol reduced the risk of recurrent gastrointestinal bleeding and the mortality rate during the 2-year period of continuous oral administration of the drug.