β‐blocker therapy for prophylaxis of initial variceal hemorrhage: Has its time come?

In a double‐blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol‐treated patients (from 18.1 ± 4.2 to 15.7 ± 3.4 mm Hg; P < 0.05) but not in patients receiving the placebo (19.6 ± 6.8 to 17.5 ± 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol‐treated group at all times (P < 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo‐, 2 propranolol‐treated; P < 0.01), all of whom had a hepatic venous pressure gradient > 12 mm Hg. In 21 patients (14 propranolol‐, 7 placebo‐treated) the hepatic venous pressure gradient decreased to ⩽12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo‐, 1 propranololtreated; P < 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to < 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.