Merkel et al. (2004) A placebo-controlled clinical trial of nadolol in the prophylaxis of growth of small esophageal varices in cirrhosis. Gastroenterology 127: 476–484

Esophageal varices, resulting from portal hypertension, are a significant complication of liver cirrhosis. As varices become larger, there is increased risk of rupture with upper gastrointestinal bleeding. Since this risk is reduced by treatment with [beta]-blockers, Merkel et al. have evaluated nadolol in the prophylaxis of growth of small varices.

Patients with cirrhosis and small esophageal varices were randomized to nadolol (n = 83) or placebo (n = 78) in a multicenter, single-blind study. Mean follow-up was 36 months and the primary endpoint was the occurrence of large esophageal varices.

Growth of esophageal varices to F2 or F3 was observed in 9 patients in the nadolol group compared with 29 in the placebo group (P < 0.001; absolute risk difference 31%; 95% confidence interval [CI] 17%–45%). Taking into account possible confounding factors (such as age and center), treatment was a significant predictor of growth of varices. Variceal bleeding, a secondary endpoint, was significantly less frequent in the nadolol group than in the placebo group (P = 0.02; absolute risk difference 10%; 95% CI 4.3%–15.7%). Once large varices had developed, however, the risk of bleeding was similar irrespective of treatment, suggesting that the observed benefit of nadolol treatment was related to the delay in progression to large varices.

Merkel et al. conclude by suggesting that [beta]-blocker prophylaxis of esophageal variceal bleeding should be started at the stage of small varices