Nonselective beta blockers are standard therapy in lowering portal venous pressure to prevent variceal bleeding in patients with cirrhosis and esophageal varices. However, it is not known if the same treatment will prevent varices from forming. Groszmann and colleagues conducted a randomized, double-blind, placebo-controlled trial of timolol (Betimol) in patients with cirrhosis and portal hypertension.
They authors enrolled 213 patients with cirrhosis and elevated portal pressures, which are defined by a hepatic venous pressure gradient of 6 mm Hg or greater. Most patients were white men. The absence of varices was proven endoscopically. In the study, there was an initial dose titration phase during which all patients received timolol, followed by a trial phase in which the patients were randomized to timolol or placebo. Patients were analyzed every three months through physical examination and laboratory assessment and underwent annual endoscopy and measurement of hepatic venous pressure gradient. Median follow-up duration was 55 months. The primary end point was the development of esophageal varices or variceal bleeding. Secondary end points included ascites, encephalopathy, liver transplant, or death.
There was no significant difference in the number of patients reaching the primary end point (42 in the timolol group [39 percent] and 42 in the placebo group [40 percent]). The two groups also were equal in reaching the secondary end points. Adverse events were more common in the group treated with timolol. The authors conclude that these findings do not support the use of nonselective beta blockers for preventing esophageal variceal formation in patients with cirrhosis and portal hypertension.