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Propranolol Compared with Propranolol plus Isosorbide-5-Mononitrate for Portal Hypertension in Cirrhosis: A Randomized Controlled Study

Joan Carles GarcÍa-Pagán, MD; Faust Feu, MD; Jaume Bosch, MD; and Joan Rodés, MD
[+] Article, Author, and Disclosure Information

Grant Support: In part by the Fundacio Catalana per a L'Estudi de les Malalties del Fetge and Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS-91/0734). Dr. GarcÍa-Pagán held a research fellowship from the FISS (89/1516).

Requests for Reprints: Jaume Bosch, MD, Hepatic Hemodynamics Laboratory, Liver Unit, Hospital Clinic i Provincial, C/. Villaroel 170, 08036 Barcelona, Spain.

Current Author Addresses: Drs. GarcÍa-Pagán, Feu, Bosch, and Rodés: Hepatic Hemodynamics Laboratory, Liver Unit, Hospital Clinic i Provincial, C/. Villaroel 170, 08036 Barcelona, Spain.

© 1991 American College of PhysiciansAmerican College of Physicians

Ann Intern Med. 1991;114(10):869-873. doi:10.7326/0003-4819-114-10-869
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Objective: To investigate whether isosorbide-5-mononitrate (Is5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis.

Design: A randomized controlled trial.

Patients: Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study.

Intervention: Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day.

Measurements: Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy.

Main Results: At 3 months, the hepatic venous pressure gradient decreased more (P < 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 ± 3.9 to 14.9 ± 3.8 mm Hg; 95% CI, - 2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 ±3.5 to 16.3 ±3.1 mm Hg; CI, - 1.1 to - 2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P < 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output.

Conclusions: The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.


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