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Drug Safety

, Volume 31, Issue 4, pp 325–334 | Cite as

Hepatic Effects of Lovastatin Exposure in Patients with Liver Disease

A Retrospective Cohort Study
  • Andrew L. Avins
  • Michele M. Manos
  • Lynn Ackerson
  • Wei Zhao
  • Rosemary Murphy
  • Theodore R. Levin
  • Douglas J. Watson
  • Peggy M. T. Hwang
  • Amy Replogle
  • Jeffrey G. Levine
Original Research Article

Abstract

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.

Keywords

Lovastatin Incidence Rate Ratio Telithromycin Adverse Hepatic Effect Lovastatin Exposure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Funding for this study was provided by Merck & Co., West Point, Pennsylvania, USA.

Drs Avins, Manos, Ackerson, Murphy and Levin have received research support and Dr Zhao has received salary support for this study from Merck & Co. Dr Watson, Dr Hwang, Ms Replogle and Dr Levine are employees of Merck & Co.

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Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Andrew L. Avins
    • 1
    • 2
    • 3
    • 4
  • Michele M. Manos
    • 1
    • 3
  • Lynn Ackerson
    • 1
  • Wei Zhao
    • 1
  • Rosemary Murphy
    • 1
  • Theodore R. Levin
    • 1
  • Douglas J. Watson
    • 5
  • Peggy M. T. Hwang
    • 5
  • Amy Replogle
    • 5
  • Jeffrey G. Levine
    • 5
  1. 1.Kaiser Permanente Division of ResearchOaklandUSA
  2. 2.Department of MedicineUniversity of CaliforniaSan FranciscoUSA
  3. 3.Department of Epidemiology & BiostatisticsUniversity of CaliforniaSan FranciscoUSA
  4. 4.Veterans Affairs Medical CenterSan FranciscoUSA
  5. 5.Merck & Co.West PointUSA

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