Carvedilol delays progression of small esophageal varices

Last Updated: 2016-07-04

By Megan Brooks

NEW YORK (Reuters Health) - Treatment with carvedilol helps delay progression of small esophageal varices in patients with cirrhosis, suggest a trial conducted in India.

"The clinical applications of the study are immense," Dr. Shiv Kumar Sarin from the Institute of Liver and Biliary Sciences in New Delhi told Reuters Health by email, "as it shows that the use of the potent non-selective beta blocker, carvedilol, in a defined group of cirrhotics with small varices, achieves a reduction in portal pressure by 8-10% and is adequate to delay progression of varices."

"This would be applicable to thousands of patients and is desirable to be used in all patients with early cirrhosis with small varices," Dr. Sarin added.

The size of varices is an important predictor of variceal hemorrhage, with the highest risk of first hemorrhage seen in patients with large varices with red color signs (15%-30% at two years), the researchers point out in their report online June 13 in Gut.

"It seems, therefore, quite logical," they say, to prevent or delay the growth of small esophageal varices to large size by reducing hepatic venous pressure gradient (HVPG).

Use of non-selective beta-blockers is the recommended therapy for reducing portal pressure and for primary prophylaxis against variceal hemorrhage in cirrhotic patients with large varices, they note.

A recent meta-analysis, however, showed that non-selective beta-blockers like propranolol are ineffective in preventing the progression of small to large varices. But the beta-blocker carvedilol has been shown to produce a greater reduction in HVPG than propranolol and to be as effective as endoscopic variceal ligation in primary prophylaxis of variceal bleeding in large esophageal varices.

Dr. Sarin and colleagues designed their study specifically to see if carvedilol helps prevent progression of small to large esophageal varices. They randomly allocated 140 consecutive patients with cirrhosis and small esophageal varices to either carvedilol or placebo. In both groups, the predominant etiology of cirrhosis was non-alcoholic fatty liver disease. The average dose of carvedilol was 12 mg per day and the target heart rate achieved was 58 beats per minute.

The researchers performed endoscopy at baseline and at six-month intervals for the next two years; they also measured HVPG at baseline and 12 months. The primary endpoint was development of large varices.

Over a treatment and follow-up period of 14 months, more patients in the carvedilol group than the placebo group were free from progression to large varices (79% vs. 61%; p=0.04), the researchers report.

Treatment with carvedilol also slowed the time to progression of small to large varices from 18.7 months in placebo group to 20.8 months in the carvedilol group (p=0.04).

Carvedilol led to a modest absolute reduction in the HVPG at one year (-8.64%), compared with 0.33% absolute increase in the HVPG with placebo, although this difference was not statistically significant.

"Only modest reduction in portal pressure achievable by carvedilol, the most promising available drug, emphasizes the need for search for newer treatment options to reduce portal pressure and hepatic fibrosis," the team says.

There were no deaths due to variceal bleeding or liver-related causes and there were no major adverse events in either group.

"Carvedilol is used in patients with large varices who have not bled from varices, and is the standard of care. This study shows that patients with small varices, in addition, would be benefitted, though the reduction in portal pressure is modest. The use of this drug is desirable to prevent growth of varices," Dr. Sarin told Reuters Health.

SOURCE: http://bit.ly/29hBRAr

Gut 2016.