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David J. Graham, MD, MPH; Judy A. Staffa, PhD; Deborah Shatin, PhD; Susan E. Andrade, ScD; Stephanie D. Schech, MPH; Lois La Grenade, MD, MPH; Jerry H. Gurwitz, MD; K. Arnold Chan, MD, ScD; Michael J. Goodman, PhD; Richard Platt, MD, MSc

JAMA. 2004;292:(doi:10.1001/jama.292.21.2585).

Context  Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available.

Objective  To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting.

Design, Setting, and Patients  Drug-specific inception cohorts of statin and fibrate users were established using claims data from 11 managed care health plans across the United States. Patients with at least 180 days of prior health plan enrollment were entered into the cohorts between January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or combined statin-fibrate therapy.

Main Outcome Measure  Incidence rates of rhabdomyolysis per 10 000 person-years of treatment, number needed to treat, and relative risk of rhabdomyolysis.

Results  In 252 460 patients treated with lipid-lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during treatment. Average incidence per 10 000 person-years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI], 0.20-0.84); for cerivastatin, 5.34 (95% CI, 1.46-13.68); and for fibrate, 2.82 (95% CI, 0.58-8.24). By comparison, the incidence during unexposed person-time was 0 (95% CI, 0-0.48; P = .056). The incidence increased to 5.98 (95% CI, 0.72-216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a fibrate, and to 1035 (95% CI, 389-2117) for combined cerivastatin-fibrate use. Per year of therapy, the number needed to treat to observe 1 case of rhabdomyolysis was 22 727 for statin monotherapy, 484 for older patients with diabetes mellitus who were treated with both a statin and fibrate, and ranged from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate.

Conclusions  Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus. Cerivastatin combined with fibrate conferred a risk of approximately 1 in 10 treated patients per year.

Author Affiliations: Office of Drug Safety, Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Md (Drs Graham, Staffa, and La Grenade); Center for Health Care Policy and Evaluation, Eden Prairie, Minn (Dr Shatin and Ms Schech); Meyers Primary Care Institute, Fallon Foundation and the University of Massachusetts Medical School, Worcester (Drs Andrade and Gurwitz); Channing Laboratory, Brigham and Women’s Hospital and Harvard Medical School (Drs Chan and Platt), Department of Ambulatory Care and Prevention, Harvard Pilgrim Health Care and Harvard Medical School (Dr Platt), and Department of Epidemiology, Harvard School of Public Health (Dr Chan), Boston, Mass; and HealthPartners Research Foundation, Minneapolis, Minn (Dr Goodman).

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RELATED LETTERS

Rhabdomyolysis and Lipid-Lowering Drugs
Alexander Tenenbaum, Enrique Z. Fisman, and Michael Motro
JAMA. 2005;293(12):1448.
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JAMA. 2005;293(12):1448-1449.
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