Multi-Center Study of the Effects of Simvastatin on Hepatic Decompensation and Death in Subjects Presenting With High-Risk Compensated Cirrhosis

Prior treatment

• Prior exposure to any statin within 6 months
• Prior allergy or sensitivity to simvastatin
• History of variceal hemorrhage confirmed endoscopically within the previous 3 years
• Presence of overt ascites or treatment with diuretics for ascites with 6 months
• Prior receipt of organ transplant
• Independent indication for initiation of statin therapy
• Need for concomitant administration of potent inhibitors of CYP34A4 enzymes (medications or other supplements that should not be taken with simvastatin, including cyclosporine, danazol, gemfibrozil, fenofibrate, extended release niacin, itraconazole, ketoconazole, voriconazole, HIV protease inhibitors, boceprevir, telaprevir, macrolide antibiotics - erythromycin, clarithromycin, telithromycin, nefazadone, amlodipine, verapamil, diltiazem, dronedarone, amiodarone, renolazine, lomitapide, and cobicistat)
• Prior TIPSS shunt

Other illness

• History of chronic, recurrent or episodic overt hepatic encephalopathy with asterixis within 6 months
• History of hepatocellular carcinoma
• Patients with any form of clinical atherosclerotic cardiovascular disease (ASCVD)

Lab values

• Patients with primary LDL-C \< 190 mg/dl
• Patients with diabetes mellitus, age 40-75 years, with LDL-C levels \>=130 mg/dl

Age

• Patients with life expectancy \< 3 years due to comorbid conditions

Other

• Child-Turcotte-Pugh C Stage (CTP Score \> 9)
• Participation in another pharmacological clinical trial within 3 months of the current study
• Pregnancy or anticipated pregnancy within 2 years
• Breast Feeding
• Hemodialysis

• U.S. Veteran
• Cirrhosis due to chronic viral hepatitis, or alcohol or non-alcoholic fatty liver
• Compensated cirrhosis (history of endoscopically-confirmed variceal hemorrhage, absence of overt ascites, history of overt non-precipitated encephalopathy)
• Age \> 18 and \<= 80
• High risk of cirrhosis decompensation as defined by any of the following:
  • Presence of esophageal varices on endoscopy
  • Presence of portosystemic collaterals on imaging as determined by a body radiologist
  • Fibroscan VCTE \>= 20kPa
  • Platelet count \<= 125 K/mm
  • 44 total points (\~50% of clinically significant portal hypertension using the ANTICIPATE Nomogram)
• Competent to provide informed consent