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

Back,ground: Carvedilol is a non-selective vasodilating beta-blocker with weak it 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&PLUSMN;0.71 to 9.27&PLUSMN;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.