Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial.
OBJECTIVE
Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis, so it could be an effective therapy for portal hypertension. This randomized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient (HVPG) and its safety in patients with cirrhosis and portal hypertension.


METHODS
Fifty-nine patients with cirrhosis and portal hypertension (HVPG > or =12 mm Hg) were randomized to groups that were given simvastatin 20 mg/day for 1 month (increased to 40 mg/day at day 15) or placebo in a double-blind clinical trial. Randomization was stratified according to whether the patient was being treated with beta-adrenergic blockers. We studied splanchnic and systemic hemodynamics and variables of liver function and safety before and after 1 month of treatment.


RESULTS
Simvastatin significantly decreased HVPG (-8.3%) without deleterious effects in systemic hemodynamics. HVPG decreases were observed in patients who were receiving beta-adrenergic blockers (-11.0%; P = .033) and in those who were not (-5.9%; P = .013). Simvastatin improved hepatic, fractional, and intrinsic clearance of indocyanine green, showing an improvement in effective liver perfusion and function. No significant changes in HVPG and liver function were observed in patients receiving placebo. The number of patients with adverse events did not differ significantly between groups. No patient was withdrawn from the study based on adverse events.


CONCLUSIONS
Simvastatin decreased HVPG and improved liver perfusion in patients with cirrhosis. These effects were additive with those of beta-adrenergic blockers. The beneficial effects of simvastatin should be confirmed in long-term clinical trials for portal hypertension.
Abraldes
Juan G
JG
Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Spain.
Albillos
Agustin
A
Bañares
Rafael
R
Turnes
Juan
J
González
Rosario
R
García-Pagán
Juan Carlos
JC
Bosch
Jaime
J
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006439:Hemodynamics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017082:Portal Pressure / Q000187:drug effects*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D019821:Simvastatin