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Statin-Associated Myopathy with Normal Creatine Kinase Levels

Paul S. Phillips, MD; Richard H. Haas, MD; Sergei Bannykh, MD, PhD; Stephanie Hathaway, RN; Nancy L. Gray, RN; Bruce J. Kimura, MD; Georgirene D. Vladutiu, PhD; John D.F. England, MD, the Scripps Mercy Clinical Research Center*

1 October 2002 | Volume 137 Issue 7 | Pages 581-585

Background: Muscle symptoms in patients who are treated with statins and have normal creatine kinase levels are not well understood.

Objective: To report biopsy-confirmed myopathy and normal creatine kinase levels associated with statin use.

Design: Case reports from preliminary analysis of an ongoing clinical trial.

Setting: Clinical research center in a community hospital.

Patients: Four patients with muscle symptoms that developed during statin therapy and reversed during placebo use.

Measurements: 1] Patients' ability to identify blinded statin therapy and 2) standard measures of functional capacity and muscle strength.

Results: All four patients repeatedly distinguished blinded statin therapy from placebo. Strength testing confirmed weakness during statin therapy that reversed during placebo use. Muscle biopsies showed evidence of mitochondrial dysfunction, including abnormally increased lipid stores, fibers that did not stain for cytochrome oxidase activity, and ragged red fibers. These findings reversed in the three patients who had repeated biopsy when they were not receiving statins. Creatine kinase levels were normal in all four patients despite the presence of significant myopathy.

Conclusion: Some patients who develop muscle symptoms while receiving statin therapy have demonstrable weakness and histopathologic findings of myopathy despite normal serum creatine kinase levels.

*For members of the Scripps Mercy Clinical Research Center, see the Appendix.

Editors' Notes Context Although severe myopathy can occur with statin therapy, some patients receiving statins develop muscle symptoms but have normal serum creatine kinase levels. Contribution This report documents biopsy-confirmed myopathy in four statin-treated patients with normal creatine kinase levels. When patients were challenged with placebo or statin, symptoms and histologic changes occurred only during statin use. Implications Normal creatine kinase levels do not rule out statin-associated myopathy in patients with muscle symptoms. The frequency of this disorder is unknown. –The Editors

 

Author and Article Information

From Scripps Mercy Hospital and University of California, San Diego, Medical Center, San Diego, California; and State University of New York at Buffalo, Buffalo, New York.

Acknowledgments: The authors thank Mr. David Cloutier for assistance with randomization sequencing and statistical analyses and Dr. Beatrice Golomb, Assistant Professor of Medicine, University of California, San Diego, for assistance with the analysis and development of epidemiologic evidence.

Potential Financial Conflicts of Interest:Grants pending: P.S. Phillips, R.H. Haas, S. Bannykh, S. Hathaway, N.L. Gray, B.J. Kimura.

Requests for Single Reprints: Paul S. Phillips, MD, Interventional Cardiology, Scripps Mercy Hospital (MER 74), 4077 Fifth Avenue, San Diego, CA 92103; Web site, impostertrial.com; e-mail, inquire{at}impostertrial.com.

Current Author Addresses: Dr. Phillips: 4060 Fourth Avenue, Suite 205, San Diego, CA 92103.

Dr. Haas: University of California San Diego Medical Center, 9500 Gilman Drive, La Jolla, CA 92093-0935.

Dr. Bannykh: Division of Neuropathology, University of California San Diego Medical Center, 225 West Dickenson Avenue, San Diego, CA 92103.

Ms. Hathaway and Ms. Gray: Cardiology Research, Scripps Mercy Hospital (MER 74), 4077 Fifth Avenue, San Diego, CA 92103.

Dr. Kimura: 230 Prospect Place, Suite 250, Coronado, CA 92118.

Dr. Vladutiu: University at Buffalo, 936 Delaware Avenue, Buffalo, NY 14209.

Dr. England: Blue Mountains Hospital, Great Western Highway, Katoomba, NSW 2780, Australia.

Author Contributions: Conception and design: P.S. Phillips, R.H. Haas, S. Hathaway, N.L. Gray, B.J. Kimura, J.D.F. England.

Analysis and interpretation of the data: P.S. Phillips, R.H. Haas, S. Bannykh, B.J. Kimura, G.D. Vladutiu, J.D.F. England.

Drafting of the article: P.S. Phillips, R.H. Haas, S. Bannykh, J.D.F. England.

Critical revision of the article for important intellectual content: P.S. Phillips, R.H. Haas, S. Bannykh, S. Hathaway, N.L. Gray, B.J. Kimura, G.D. Vladutiu.

Final approval of the article: P.S. Phillips, R.H. Haas, S. Bannykh.

Provision of study materials or patients: R.H. Haas, B.J. Kimura, J.D.F. England.

Obtaining of funding: S. Hathaway, N.L. Gray.

Administrative, technical, or logistic support: S. Hathaway, N.L. Gray.

Collection and assembly of data: P.S. Phillips, R.H. Haas, S. Hathaway, N.L. Gray, G.D. Vladutiu.

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