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Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial.
Gastroenterology. 2009 May; 136(5):1651-8.G

Abstract

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 > 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 No patient was withdrawn from the study based on adverse events.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.

Authors+Show Affiliations

Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19208350

Citation

Abraldes, Juan G., et al. "Simvastatin Lowers Portal Pressure in Patients With Cirrhosis and Portal Hypertension: a Randomized Controlled Trial." Gastroenterology, vol. 136, no. 5, 2009, pp. 1651-8.
Abraldes JG, Albillos A, Bañares R, et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology. 2009;136(5):1651-8.
Abraldes, J. G., Albillos, A., Bañares, R., Turnes, J., González, R., García-Pagán, J. C., & Bosch, J. (2009). Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology, 136(5), 1651-8. https://doi.org/10.1053/j.gastro.2009.01.043
Abraldes JG, et al. Simvastatin Lowers Portal Pressure in Patients With Cirrhosis and Portal Hypertension: a Randomized Controlled Trial. Gastroenterology. 2009;136(5):1651-8. PubMed PMID: 19208350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. AU - Abraldes,Juan G, AU - Albillos,Agustin, AU - Bañares,Rafael, AU - Turnes,Juan, AU - González,Rosario, AU - García-Pagán,Juan Carlos, AU - Bosch,Jaime, Y1 - 2009/01/24/ PY - 2008/08/13/received PY - 2009/01/13/revised PY - 2009/01/22/accepted PY - 2009/2/12/entrez PY - 2009/2/12/pubmed PY - 2009/5/16/medline SP - 1651 EP - 8 JF - Gastroenterology JO - Gastroenterology VL - 136 IS - 5 N2 - 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 > 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. SN - 1528-0012 UR - https://www.unboundmedicine.com/medline/citation/19208350/Simvastatin_lowers_portal_pressure_in_patients_with_cirrhosis_and_portal_hypertension:_a_randomized_controlled_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(09)00144-9 DB - PRIME DP - Unbound Medicine ER -