Autoimmune, Cholestatic and Biliary Disease
Article first published online: 1 AUG 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 5, pages 1453–1463, November 2007
How to Cite
Lewis, J. H., Mortensen, M. E., Zweig, S., Fusco, M. J., Medoff, J. R. and Belder, R. (2007), Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology, 46: 1453–1463. doi: 10.1002/hep.21848
This article was presented in part at the 57th annual meeting of the American Association for the Study of Liver Diseases, October 31, 2006, Boston, MA. Clinical trial registration number NCT00529178, available at: http://clinicaltrials.gov
Potential conflict of interest: Dr. Lewis is a consultant for Bristol-Myers Smith. Dr. Mortenson owns stock in and is an employee of Bristol-Myers Smith. Dr. Fusco owns stock in Astra and Bristol-Myers Smith. He is an employee of Johnson and Johnson. Dr. Belder owns stock in Bristol-Myers Squibb.
The names and locations of the investigators are provided in the appendix.
- Issue published online: 29 OCT 2007
- Article first published online: 1 AUG 2007
- Manuscript Accepted: 1 JUN 2007
- Manuscript Received: 23 FEB 2007
The hepatotoxic potential of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors in patients with underlying chronic liver disease remains controversial. We performed a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial that compared pravastatin (80 mg) to a placebo administered once daily to hypercholesterolemic subjects greater than 18 years of age with at least a 6-month history of compensated chronic liver disease and with a low-density lipoprotein cholesterol (LDL-C) level greater than or equal to 100 mg/dL and a triglyceride (TG) level lower than 400 mg/dL. The efficacy was determined by the percentage change in LDL-C [along with the total cholesterol (TC), high-density lipoprotein cholesterol, and TG] from the baseline to week 12. The safety was analyzed by the proportion of subjects who developed at least 1 alanine aminotransferase (ALT) value greater than or equal to 2 times the upper limit of normal for those with normal ALT at the baseline or a doubling of the baseline ALT for those with elevated ALT at the baseline during 36 weeks of treatment. A total of 630 subjects were screened, and 326 subjects were randomized; nonalcoholic fatty liver disease was present in 64%, and chronic hepatitis C was present in 23%. In the intent-to-treat population, pravastatin (80 mg/day) significantly lowered the mean LDL-C, TC, and TG values at week 12 and at other times (weeks 4, 8, 24, and 36) in comparison with the placebo. The incidence of subjects who met the primary prespecified ALT event definition was lower in the pravastatin group at all times over the 36 weeks of therapy in comparison with the placebo group, although the difference was not statistically significant. No differences were seen on the basis of the baseline ALT values or among the different liver disease groups. Conclusion: High-dose pravastatin (80 mg/day) administered to hypercholesterolemic subjects with chronic liver disease significantly lowered LDL-C, TC, and TGs in comparison with the placebo and was safe and well tolerated. The concern over an increased potential for statin-induced hepatotoxicity in patients with chronic liver disease appears to be lessened on the basis of these results. (HEPATOLOGY 2007.)