Hepatic effects of lovastatin exposure in patients with liver disease: a retrospective cohort study.
BACKGROUND
Little is known about the potential adverse hepatic effects of HMG-CoA reductase inhibitors ('statins') in patients with existing liver disease; therefore, we examined the risk of liver toxicity with lovastatin exposure in these patients.


METHODS
A retrospective cohort study was performed using data from a large integrated health plan in Northern California, USA. Patients with laboratory or clinical evidence of liver disease were identified and their exposure to lovastatin was determined. The primary outcome was a pattern of liver-test abnormalities associated with a poor prognosis among patients with drug-induced liver disease, based on Hy's Rule. Secondary outcomes included liver injury (defined as moderate or severe, depending on the degree of ALT level elevations) or the development of either clinical cirrhosis or liver failure. Incidence rate ratios (IRRs) were calculated and multivariate analyses conducted using extended Cox models.


RESULTS
A total of 93 106 patients met the entry criteria. Lovastatin exposure was associated with a lower incidence of all endpoints, including the primary outcome (IRR = 0.28, 95% CI 0.12, 0.55), moderate liver injury (IRR = 0.56, 95% CI 0.47, 0.65), severe liver injury (IRR = 0.50, 95% CI 0.29, 0.81) and the occurrence of either cirrhosis or liver failure (IRR = 0.29, 95% CI 0.21, 0.38); adjustment for age and sex resulted in some attenuation of this reduction in incidence. The observed effects were generally consistent across a range of baseline liver-disease diagnoses and greater cumulative lovastatin exposure was associated with fewer outcome events for some endpoints.


CONCLUSIONS
In this retrospective analysis, exposure to lovastatin was not associated with an increased risk of adverse hepatic outcomes. These results do not support concern regarding lovastatin-related hepatotoxicity in patients with existing liver disease.
Avins
Andrew L
AL
Kaiser Permanente Division of Research, Oakland, CA 94612, USA. andrew.avins@ucsf.edu
Manos
Michele M
MM
Ackerson
Lynn
L
Zhao
Wei
W
Murphy
Rosemary
R
Levin
Theodore R
TR
Watson
Douglas J
DJ
Hwang
Peggy M T
PM
Replogle
Amy
A
Levine
Jeffrey G
JG
D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D015331:Cohort Studies; D003327:Coronary Disease / Q000517:prevention & control; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008107:Liver Diseases / Q000503:physiopathology; D008111:Liver Function Tests; D008148:Lovastatin / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D018570:Risk Assessment
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase