Isosorbide mononitrate with nadolol compared to nadolol alone for prevention of the first bleeding in cirrhosis. A double-blind placebo-controlled randomised trial

β-blockers are recommended for prevention of first variceal bleeding in cirrhosis. Isosorbide mononitrate enhances portal pressure lowering effect of propranolol and causes a significant portal pressure reduction even in non responders to propranolol. In a double-blind placebo-controlled trial, we compared isosorbide mononitrate and nadolol with placebo and nadolol to prevent the first bleeding in cirrhotic patients at high risk. A total of 57 cirrhotic patients with large esophageal varices and red color signs who had never bled, were randomly assigned to isosorbide mononitrate (40 mg twice a day) and nadolol (maximum tolerated dose with heart rate >55) (n=30) or to placebo and nadolol (n=27). Any episode of hematemesis or melena, after randomisation, was considered as treatment failure. After a mean follow-up of 31±14 months, 22 patients bled: 13 in the placebo group (48%) and 9 in the mononitrate group (30%) (p=0.16). Deaths were 9 (33%) and 10 (33%), respectively (p=1.00). The incidence of ascites showed no difference in the two groups. Side effects were significantly more frequent in the mononitrate group. Six patients in the placebo and 15 in the mononitrate group were withdrawn from treatment mainly on account of side effects or poor compliance. During the per protocol treatment period (20±15 and 18±15 months, respectively) 12 (44%) patients in the placebo and 4 (13%) in the mononitrate group bled (p=0.009). In conclusion, results suggest that the association of isosorbide 5-mononitrate and nadolol, at the doses used in this study, might reduce the risk of portal hypertensive bleeding compared with nadolol alone, in patients who tolerate treatment.