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 less than 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 less than 0.001). Variceal
hemorrhage occurred in 13 patients (11 placebo-, 2
propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14
propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal 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
propranolol-treated; P less than 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 less than 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.