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

Background: Carvedilol is a non‐selective vasodilating β‐blocker with weak α1 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

Randomised controlled trial of long term portographic follow up versus variceal band ligation following transjugular intrahepatic portosystemic stent shunt for preventing oesophageal variceal rebleeding

Background/aims: Transjugular intrahepatic portosystemic stent shunt (TIPSS) is effective in the prevention of variceal rebleeding but requires invasive portographic follow up. This randomised controlled trial aims to test the hypothesis that combining variceal band ligation (VBL) with TIPSS can obviate the need for long term TIPSS surveillance without compromising clinical efficacy, and can reduce the incidence of hepatic encephalopathy. Patients/methods: Patients who required TIPSS for the prevention of oesophageal variceal rebleeding were randomised to either TIPSS alone (n = 39, group 1) or TIPSS plus VBL (n = 40, group 2). In group 1, patients underwent long term TIPSS angiographic surveillance. In group 2, patients entered a banding programme with TIPSS surveillance only continued for up to one year. Results: There was a tendency to higher variceal rebleeding in group 2 although this did not reach statistical significance (8% v 15%; relative hazard 0.58; 95% confidence interval (CI) 0.15–2.33; p = 0.440). Mortality (47% v 40%; relative hazard 1.31; 95% CI 0.66–2.61; p = 0.434) was similar in the two groups. Hepatic encephalopathy was significantly less in group 2 (20% v 39%; relative hazard 2.63; 95% CI 1.11–6.25; p = 0.023). Hepatic encephalopathy was not statistically different after correcting for sex and portal pressure gradient (p = 0.136). Conclusions: TIPSS plus VBL without long term surveillance is effective in preventing oesophageal variceal rebleeding, and has the potential for low rates of encephalopathy. Therefore, VBL with short term TIPSS surveillance is a suitable alternative to long term TIPSS surveillance in the prevention of oesophageal variceal rebleeding