PROPRANOLOL PLUS MOLSIDOMINE VS PROPRANOLOL ALONE IN THE TREATMENT OFPORTAL-HYPERTENSION IN PATIENTS WITH CIRRHOSIS

Background/aims: Effective protection from the risk of variceal bleedi ng is achieved when the hepatic venous pressure gradient is reduced to 12 mmHg or at least by 20% of baseline values, Such a marked decrease is rarely achieved with propranolol, and new agents or combinations o f them are now being explored, The present randomized study investigat ed whether chronic treatment with the combination of propranolol plus molsidomine, a preferential venous dilator that reduces hepatic venous pressure gradient and does not cause pharmacological tolerance, achie ves greater reduction in hepatic venous pressure gradient than propran olol alone. Methods: A hemodynamic study was performed in 34 patients with cirrhosis with portal hypertension in baseline conditions and aft er 3 months of chronic oral treatment with propranolol alone (n=19) or propranolol plus molsidomine (n=15). Results: Propranolol produced a significant reduction in hepatic venous pressure gradient (-16%, p<0.0 1), Propranolol plus molsidomine also caused a slight but significant decrease in hepatic venous pressure gradient (-9%, p<0.05).Hepatic blo od flow and the hepatic and intrinsic clearance of indocyanine green w ere significantly reduced by propranolol, The combined administration of propranolol + molsidomine significantly reduced hepatic blood flow but not hepatic and intrinsic clearance of indocyanine green, Both tre atment groups produced similar reduction in azygos blood how heart rat e and cardiac output, However, contrary to propranolol alone, proprano lol plus molsidomine did not increase cardiopulmonary pressures. Concl usions: The current study shows that although the combined administrat ion of propranolol plus molsidomine prevents some of the adverse effec ts of propranolol on liver function and cardiopulmonary pressures, it does not achieve a greater reduction in hepatic venous pressure gradie nt than propranolol alone and therefore, does not support the use of t his combined therapy for the pharmacological treatment of portai hyper tension.