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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*
[+] Article, Author, and Disclosure 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@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.

Ann Intern Med. 2002;137(7):581-585. doi:10.7326/0003-4819-137-7-200210010-00009
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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.


Grahic Jump Location
Muscle biopsy specimens obtained while patients were receiving and not receiving statin therapy.parts A, C, and Eparts B, D, and F

These oil red O stains show lipid as red-staining bodies. All specimens obtained from trial patients 1, 2, and 3 during statin therapy ( , respectively) showed an unusual accumulation of lipid in type 1 fibers. These lipid accumulations had resolved upon repeated biopsy done when the patients were no longer receiving statins ( , respectively). (Oil red O stains; original magnification, ×20).

Grahic Jump Location




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Summary for Patients

Muscle Abnormalities in Four Patients Taking Statins To Treat Unfavorable Cholesterol Levels

The summary below is from the full report titled “Statin-Associated Myopathy with Normal Creatine Kinase Levels.” It is in the 1 October 2002 issue of Annals of Internal Medicine (volume 137, pages 581-585). The authors are PS Phillips, RH Haas, S Bannykh, S Hathaway, NL Gray, BJ Kimura, GD Vladutiu, JDF England, and the Scripps Mercy Clinical Research Center.


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