Endoscopic ligation compared with combined treatment with nadolol and isosorbide mononitrate to prevent recurrent variceal bleeding

Background: After an episode of acute bleeding from esophageal varices, patients are at high risk for recurrent bleeding and death. We compared two treatments to prevent recurrent bleeding -- endoscopic ligation and combined medical therapy with nadolol and isosorbide mononitrate. Methods: We randomly assigned 144 patients with cirrhosis who were hospitalized with esophageal variceal bleeding to receive treatment with endoscopic ligation (72 patients) or the combined medical therapy (72 patients). Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The mean (+/-SD) dose of nadolol was 96+/-56 mg per day, and the mean dose of isosorbide was 66+/-22 mg per day. The primary end points were recurrent bleeding, complications, and death. Results: The median follow-up period was 21 months. A total of 35 patients in the ligation group and 24 in the medication group had recurrent bleeding. The probability of recurrence was lower in the medication group, both for all episodes related to portal hypertension (P=0.04) and for recurrent variceal bleeding (P=0.04). There were major complications in nine patients treated with ligation (seven had bleeding esophageal ulcers and two had aspiration pneumonia) and two treated with medication (both had bradycardia and dyspnea) (P=0.05). Thirty patients in the ligation group died, as did 23 patients in the medication group (P=0.52). The probability of recurrent bleeding was lower for patients with a hemodynamic response to therapy, defined as a decrease in the hepatic venous pressure gradient of more than 20 percent from the base-line value or to less than 12 mm Hg (18 percent, vs. 54 percent in patients with no hemodynamic response at one year; P<0.001), and the probability of survival was higher (94 percent vs. 78 percent at one year, P=0.02). Conclusions: Combined therapy with nadolol and isosorbide mononitrate is more effective than endoscopic ligation for the prevention of recurrent bleeding and is associated with a lower rate of major complications. (N Engl J Med 2001;345:647-55.) Copyright (C) 2001 Massachusetts Medical Society.