Clinical trial: a randomized controlled study on prevention of variceal rebleeding comparing nadolol + ligation vs. hepatic venous pressure gradient-guided pharmacological therapy

Aliment Pharmacol Ther. 2009 Feb 15;29(4):397-408. doi: 10.1111/j.1365-2036.2008.03880.x. Epub 2008 Nov 1.

Abstract

Background: Hepatic venous pressure gradient (HVPG) monitoring of therapy to prevent variceal rebleeding provides strong prognostic information. Treatment of nonresponders to beta-blockers +/- nitrates has not been clarified.

Aim: To assess the value of HVPG-guided therapy using nadolol + prazosin in nonresponders to nadolol + isosorbide-5-mononitrate (ISMN) compared with a control group treated with nadolol + ligation.

Methods: Cirrhotic patients with variceal bleeding were randomized to HVPG-guided therapy (n = 30) or nadolol + ligation (n = 29). A Baseline haemodynamic study was performed and repeated within 1 month. In the guided-therapy group, nonresponders to nadolol + ISMN received nadolol and carefully titrated prazosin and had a third haemodynamic study.

Results: Nadolol + prazosin decreased HVPG in nonresponders to nadolol + ISMN (P < 0.001). Finally, 74% of patients were responders in the guided-therapy group vs. 32% in the nadolol + ligation group (P < 0.01). The probability of rebleeding was lower in responders than in nonresponders in the guided therapy group (P < 0.01), but not in the nadolol + ligation group (P = 0.41). In all, 57% of nonresponders rebled in the guided-therapy group and 20% in the nadolol + ligation group (P = 0.05). The incidence of complications was similar.

Conclusions: In patients treated to prevent variceal rebleeding, the association of nadolol and prazosin effectively rescued nonresponders to nadolol and ISMN, improving the haemodynamic response observed in controls receiving nadolol and endoscopic variceal ligation. Our results also suggest that ligation may rescue nonresponders.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects*
  • Drug Therapy, Combination
  • Esophageal and Gastric Varices / complications
  • Esophageal and Gastric Varices / drug therapy*
  • Female
  • Follow-Up Studies
  • Gastrointestinal Hemorrhage / etiology
  • Gastrointestinal Hemorrhage / prevention & control*
  • Hemodynamics / drug effects
  • Humans
  • Isosorbide Dinitrate / administration & dosage
  • Isosorbide Dinitrate / adverse effects
  • Isosorbide Dinitrate / analogs & derivatives*
  • Ligation / methods*
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy*
  • Male
  • Middle Aged
  • Nadolol / administration & dosage*
  • Nadolol / adverse effects
  • Secondary Prevention
  • Venous Pressure / drug effects

Substances

  • Antihypertensive Agents
  • Nadolol
  • Isosorbide Dinitrate
  • isosorbide-5-mononitrate