Isosorbide mononitrate and propranolol compared with propranolol alone forthe prevention of variceal rebleeding

The aim of this study was to test the effectiveness of isosorbide-S-mononit rate (IM) as an adjunct to propranolol (PR) in the prevention of variceal r ebleeding. Ninety-five cirrhotic patients with variceal bleeding were rando mly assigned to treatment with PR + IM (46 patients) or PR alone (49 patien ts). Eighteen patients in the PR + IM group and 28 in the PR group had rebl eeding during the 2 years after randomization. The actuarial probability of rebleeding 2 years after randomization was lower in the PR + IM group (40. 4% vs. 57.4%) but the difference was not significant (P = .09). However, th e decrease in the risk of rebleeding reached statistical significance after stratification according to age, i.e. less than 50 versus greater than or equal to 50 years old, (P = .03) or by adding an additional pear of follow- up (P = .05). No significant difference was found in rebleeding index and s urvival. The multivariate Cox analysis indicated first, that both treatment (P = .03) and age (P = .001) were factors predictive of rebleeding and sec ond, that PR + MI reduced the risk of rebleeding by half (relative risk: 0. 51, 95% confidence interval: 0.28-0.95). Seven patients in the PR + MI grou p and 1 patient in the PR group had to discontinue one of the drugs because of adverse events (P = .03). These results suggest that the addition of IM improves the efficacy of PR alone in the prevention of variceal rebleeding in cirrhotic patients. However no beneficial effects were observed on othe r parameters reflecting the efficacy of treatment.