Simvastatin Lowers Portal Pressure in Patients With Cirrhosis and Portal Hypertension: A Randomized Controlled Trial
Background & Aims
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 ≥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 β-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 β-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 No patient was withdrawn from the study based on adverse events.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 β-adrenergic blockers. The beneficial effects of simvastatin should be confirmed in long-term clinical trials for portal hypertension.
Abbreviations used in this paper: CK, creatin phosphokinase, HVPG, hepatic venous pressure gradient
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J.G.A. and A.A. contributed equally to this work and share first authorship.
Conflicts of interest The authors disclose no conflicts. The statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically serious adverse events as defined in federal guidelines) have been confirmed independently by a biostatistician (Juan G. Abraldes, MD) who is not employed by the corporate entity. The corresponding author had full access to all of the data and takes full responsibility for the veracity of the data and analysis.
Funding Supported by Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, and the Spanish Ministry of Science and Innovation (grants CM0300123, 05/1285, 05/0519, and 06/0623). The Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas is funded by the Instituto de Salud Carlos III. The trial sponsor had no involvement in the design of the trial, collection and analysis of the data, or writing of the report.
Trial registration number: NCT00594191.
PII: S0016-5085(09)00144-9
doi:10.1053/j.gastro.2009.01.043
© 2009 AGA Institute. Published by Elsevier Inc. All rights reserved.
