Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating beta-blocker, in patients with cirrhosis and portal hypertension

Aliment Pharmacol Ther. 2002 Mar;16(3):373-80. doi: 10.1046/j.1365-2036.2002.01190.x.

Abstract

Background: Carvedilol is a non-selective vasodilating beta-blocker with weak alpha1 receptor antagonism. Recent studies have demonstrated its potential as a portal hypotensive agent.

Aim: To assess the haemodynamic effects and patient tolerability of the acute and chronic administration of low-dose carvedilol.

Methods: Haemodynamic measurements were performed in ten cirrhotic patients before and 1 h after the administration of 12.5 mg oral carvedilol. The study was repeated 4 weeks after daily administration of 12.5 mg carvedilol.

Results: After acute administration of carvedilol, there was a 23% reduction in the hepatic venous pressure gradient from 16.37 +/- 2.14 to 12.56 +/- 3.91 mmHg (P < 0.05), with significant falls in the heart rate, mean arterial pressure and cardiac output. Chronic administration resulted in a further fall in the hepatic venous pressure gradient from a baseline of 16.37 +/- 0.71 to 9.27 +/- 1.40 mmHg (P < 0.001) with the mean arterial pressure being unaffected. The drug was well tolerated with only one patient experiencing asymptomatic hypotension.

Conclusions: The results show that low-dose carvedilol is an extremely potent portal hypotensive pharmacological agent, and is worthy of further investigation in large randomized trials to assess its effect in preventing variceal haemorrhage.

Publication types

  • Clinical Trial

MeSH terms

  • Carbazoles / administration & dosage*
  • Carbazoles / adverse effects
  • Carbazoles / pharmacology*
  • Carbazoles / therapeutic use
  • Carvedilol
  • Drug Administration Schedule
  • Female
  • Hemodynamics / drug effects*
  • Humans
  • Hypertension, Portal / complications
  • Hypertension, Portal / drug therapy
  • Hypertension, Portal / physiopathology*
  • Kidney Function Tests
  • Liver / blood supply
  • Liver / drug effects
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / physiopathology*
  • Liver Function Tests
  • Male
  • Propanolamines / administration & dosage*
  • Propanolamines / adverse effects
  • Propanolamines / pharmacology*
  • Propanolamines / therapeutic use
  • Regional Blood Flow / drug effects
  • Vasodilator Agents / administration & dosage*
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / pharmacology*
  • Vasodilator Agents / therapeutic use

Substances

  • Carbazoles
  • Propanolamines
  • Vasodilator Agents
  • Carvedilol