Randomized, controlled trial of carvedilol versus nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding

J Gastroenterol Hepatol. 2012 Nov;27(11):1681-7. doi: 10.1111/j.1440-1746.2012.07244.x.

Abstract

Background and aim: Carvedilol has been shown to be more effective than propranolol in decreasing portal pressure. Sufficient data from controlled trials remains limited. This trial compared the relative safety and efficacy between carvedilol and nadolol plus isosorbide mononitrate in preventing variceal rebleeding.

Methods: After successful control of acute esophageal variceal bleeding, eligible patients were randomized to the carvedilol group, 61 patients, using carvedilol 6.25-12.5 mg daily or the N + I group, 60 patients, using nadolol 40-80 mg plus isorsorbide-5-mononitrate 20 mg daily. The end points were rebleeding from varices, adverse events or death.

Results: After a median follow up of 30 months, recurrent upper gastrointestinal bleeding developed in 37 patients (61%) in the carvedilol group and 37 patients (62%) in the N + I group (P = 0.90). Recurrent bleeding from esophageal varices occurred in 31 patients (51%) in the carvedilol group and in 26 patients (43%) in the N + I group (P = 0.46). Recurrent bleeding from gastric varices occurred in two patients (3%) in the carvedilol group and in eight patients (13%) in the N + I group (P = 0.05). Severe adverse events occurred in one patient in the carvedilol group and 17 patients in the N + I group (P < 0.0001). Fifteen patients of the carvedilol group and 17 patients in the N + I group died (P = 0.83). Two patients in the carvedilol group and three patients in the N + I group died of variceal bleeding.

Conclusions: Carvedilol was as effective as nadolol plus isorsorbide-5 -mononitrate mononitrate in the prevention of gastroesophageal variceal rebleeding with fewer severe adverse events and similar survival.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure
  • Carbazoles / adverse effects
  • Carbazoles / therapeutic use*
  • Carvedilol
  • Chi-Square Distribution
  • Drug Therapy, Combination / adverse effects
  • Esophageal and Gastric Varices / complications*
  • Esophageal and Gastric Varices / surgery
  • Female
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Hemorrhage / prevention & control*
  • Gastrointestinal Hemorrhage / surgery
  • Hemostasis, Endoscopic
  • Humans
  • Hypertension, Portal / complications
  • Hypertension, Portal / drug therapy*
  • Isosorbide Dinitrate / adverse effects
  • Isosorbide Dinitrate / analogs & derivatives*
  • Isosorbide Dinitrate / therapeutic use
  • Kaplan-Meier Estimate
  • Ligation
  • Male
  • Middle Aged
  • Nadolol / adverse effects
  • Nadolol / therapeutic use*
  • Propanolamines / adverse effects
  • Propanolamines / therapeutic use*
  • Proportional Hazards Models
  • Secondary Prevention
  • Vasodilator Agents / therapeutic use

Substances

  • Antihypertensive Agents
  • Carbazoles
  • Propanolamines
  • Vasodilator Agents
  • Carvedilol
  • Nadolol
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate