Haemodynamic effects of acute and chronic administration of low-dose carvedilol, a vasodilating b-blocker, in patients with cirrhosis and portal hypertension D. TRIPATHI, G. THERAPONDOS, H. F. LUI, A. J. STANLEY & P. C. HAYES Liver Unit, Department of Medicine, Royal In®rmary of Edinburgh, Edinburgh, UK Accepted for publication 15 October 2001 INTRODUCTION The haemodynamic effects of propranolol have been well studied. Lebrec et al. demonstrated a greater than 20% reduction in the hepatic venous pressure gradient (HVPG) following the acute administration of propran- olol, 1 but up to one-third of patients do not exhibit a portal hypotensive response. 2 This may be explained by a portal hypertensive model demonstrating that a rise in the portocollateral resistance accompanies the reduc- tion in portal blood ¯ow, thus reducing the overall portal hypotensive response to propranolol. 3 Current evidence suggests that the goal of pharmacotherapy in reducing the risk of variceal haemorrhage is to achieve a fall in the HVPG to £ 12 mmHg 4 or a 20% 5 reduction from baseline values. The role of non-selective b-blockers in the primary prevention of variceal haemorrhage has been exten- sively studied. 6±14 Meta-analysis of these trials has clearly shown the bene®t of these drugs when compared with placebo. 15 However, many patients are intolerant to drug side-effects. 10, 13 a 1 antagonism has been investigated in three haemo- dynamic studies. 16±18 Impressive reductions in the HVPG were achieved and these were comparable with SUMMARY Background: Carvedilol is a non-selective vasodilating b-blocker with weak a 1 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 per- formed 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 signi®cant 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 pharmacolo- gical agent, and is worthy of further investigation in large randomized trials to assess its effect in preventing variceal haemorrhage. Correspondence to: Dr D. Tripathi, Department of Medicine, Royal In®rmary of Edinburgh, Lauriston Place, Edinburgh, EH3 9YW, UK. E-mail: d.tripathi@ed.ac.uk Aliment Pharmacol Ther 2002; 16: 373±380. Ó 2002 Blackwell Science Ltd 373