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, pat ients are at high risk for recurrent bleeding and death. We compared two tr eatments 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 hospital ized with esophageal variceal bleeding to receive treatment with endoscopic ligation (72 patients) or the combined medical therapy (72 patients). Sess ions of ligation were repeated every two to three weeks until the varices w ere eradicated. The mean (+/-SD) dose of nadolol was 96+/-56 mg per day, an d the mean dose of isosorbide was 66+/-22 mg per day. The primary end point s 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 var iceal bleeding (P=0.04). There were major complications in nine patients tr eated with ligation (seven had bleeding esophageal ulcers and two had aspir ation pneumonia) and two treated with medication (both had bradycardia and dyspnea) (P=0.05). Thirty patients in the ligation group died, as did 23 pa tients in the medication group (P=0.52). The probability of recurrent bleed ing was lower for patients with a hemodynamic response to therapy, defined as a decrease in the hepatic venous pressure gradient of more than 20 perce nt from the base-line value or to less than 12 mm Hg (18 percent, vs. 54 pe rcent in patients with no hemodynamic response at one year; P<0.001), and t he probability of survival was higher (94 percent vs. 78 percent at one yea r, P=0.02). Conclusions: Combined therapy with nadolol and isosorbide mononitrate is mo re effective than endoscopic ligation for the prevention of recurrent bleed ing and is associated with a lower rate of major complications. (N Engl J M ed 2001;345:647-55.) Copyright (C) 2001 Massachusetts Medical Society.