Addition of propranolol and isosorbide mononitrate to endoscopic variceal ligation does not reduce variceal rebleeding incidence

Background & Aims: Endoscopic variceal ligation (EVL) and propranolol are standard secondary prophylaxis therapies for variceal bleeding. Addition of isosorbide mononitrate (ISMN) to propranolol improves its hemodynamic efficacy; we investigated whether a combination of EVL and propranolol/ISMN was more effective than EVL alone for secondary prophylaxis. Methods: Patients with a prior variceal bleed were randomly assigned to groups given a combination (n = 88) of EVL, propranolol (dose titrated to reduce heart rate to 55 beats per minute), and ISMN (40 mg/day) or EVL alone (n = 89). Primary end points were rebleeding or death; secondary end points were new complications of portal hypertension or serious adverse effects. Results: The actuarial probabilities of rebleeding 2 years after therapy were 27% in the combination group and 31% in the EVL alone group (P = .822). Two patients in the combination group and 3 patients in the EVL alone group died during the study period (P = .682); no deaths were caused by variceal hemorrhage. In cirrhotic patients, the actuarial probabilities of rebleeding were 24% and 30%, respectively (P = .720). Secondary end points were comparable between groups. In multivariate analyses, presence of ascites (P = .003), serum albumin < 3.3 g/dL (P = .008), and hepatic venous pressure gradients > or = 18 mm Hg (P = .009) were independent risk factors for variceal rebleeding. Conclusions: EVL alone is sufficient to prevent variceal rebleeding in cirrhotic and noncirrhotic patients with history of variceal bleeding. Addition of propranolol and ISMN to EVL does not reduce the incidence of variceal rebleeding but increases severe adverse effects. Risk factors for rebleeding include ascites, low serum albumin, and high hepatic venous pressure gradients