A nonselective beta-blocker did not prevent gastroesophageal varices in cirrhosis and portal hypertension.

M e t h o d s Design: Randomized placebo-controlled trial. Allocation: {Concealed}†.* Blinding: Blinded {clinicians, patients, data collectors, outcome assessors, and data analysts}†.* Follow-up period: Median 55 months (range 0 to 99 mo). Setting: 4 centers in Barcelona, Spain; West Haven, Connecticut, and Boston, Massachusetts, USA; and London, United Kingdom. Patients: 213 patients 18 to 74 years of age (mean 45 y, 59% men) with cirrhosis and portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) and without gastroesophageal varices. Exclusion criteria included ascites, hepatocellular carcinoma, splenic or portal vein thrombosis, life-threatening concurrent illness, and primary biliary cirrhosis or sclerosing cholangitis. Intervention: Oral timolol, median 11 mg (n = 108), or placebo, median 13 mg (n = 105) daily. The dose (range 1.25 to 80 mg) was based on prerandomization titration with timolol. Outcomes: A composite endpoint of development of varices or variceal hemorrhage. Secondary outcomes were a composite of ascites, hepatic encephalopathy, liver transplantation, or death; treatment failure (primary endpoint, transplantation, or death); and adverse events. Patient follow-up: 100% (intention-to-treat analysis).