Clinical

Beta blockade fails to prevent gastroesophageal varices

Last Updated: 2005-11-23 17:00:13 -0400 (Reuters Health)

NEW YORK (Reuters Health) - The beta-blocker timolol does not prevent gastroesophageal varices from forming in patients with cirrhosis, a multinational team of investigators reports.

Beta blockers are used to prevent variceal hemorrhage in patients who already have gastroesophageal varices, Dr. Roberto J. Groszmann, from Yale University School of Medicine in New Haven, Connecticut, and colleagues note in their report, published in the New England Journal of Medicine for November 24.

They theorized that early use of timolol would prevent varices from forming in the first place, and studied 213 patients with cirrhosis and a hepatic venous pressure gradient (HVPG) of at least 6 mm Hg. A total of 108 patients were randomly assigned to timolol, titrated up to a maximum dose of 80 mg/day (median 10.8 mg), and 105 were assigned to placebo.

During median follow-up of 54.9 months, there was no significant difference between groups in the primary end point of variceal formation or hemorrhage (39% versus 40%, p = 0.89).

There was also no significant difference in the secondary endpoints of ascites, encephalopathy, liver transplantation or death.

However, the authors did find that a baseline HVPG of 10 mm Hg or more was independently predictive of reaching the primary end point, and an HVPG reduction of 10% or more from baseline was associated with a significant decrease in variceal formation and hemorrhage.

"An important finding was that more patients in the timolol group than in the placebo group had these favorable HVPG responses," Dr. Groszmann and his team note, "indicating that timolol had a beneficial effect, but one that was not sufficient to tip the balance in favor of beta-blockers," since timolol was associated with an increased risk of adverse events.

"A reduction in the HVPG by more than 10 percent... should be the goal in the pharmacologic prevention of gastroesophageal varices," they conclude.

In an accompanying editorial, Dr. Sandeep Mukherjee and Dr. Michael F. Sorrell, both from the University of Nebraska Medical Center in Omaha, encourage physicians to monitor HVPG in patients with cirrhosis.

Moreover, they advise that the findings by Dr. Groszmann's team "should not affect current recommendations to use beta-blockers, alone or in conjunction with endoscopic banding, to prevent bleeding in patients with established esophageal varices."

N Engl J Med 2005;353:2254-2261,2288-2290.