A controlled clinical trial of cimetidine in the recurrence of variceal hemorrhage: implications about the pathogenesis of hemorrhage.

In a prospective randomized double-blind controlled trial, 51 patients, 16 with cirrhosis and 35 with extrahepatic portal hypertension all of whom presented with variceal bleeding, were given either long-term cimetidine in a dosage of 1.6 gm daily (24 patients) or placebo tablets (27 patients). Thirty-eight patients completed 2 years of treatment. For 16 patients with cirrhosis, there was no significant difference in the frequency of rebleeding between the cimetidine (62.5%) and placebo (75.0%) groups. Similarly, in 35 patients with extrahepatic portal hypertension, the frequency with which bleeding recurred in the cimetidine (37.5%) and placebo groups (36.8%) was not significantly different. Gastric acid and esophageal function studies, including basal acid output, lower esophageal sphincter pressure, esophageal acid reflux, and clearance measurements, showed no significant differences between patients with cirrhosis or extrahepatic portal hypertension both before and after variceal bleeding and in healthy control subjects. These results suggest that it is unlikely that gastric acid reflux is a significant factor in the pathogenesis of variceal hemorrhage, and cimetidine does not prevent recurrent episodes of bleeding.