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CARDIOLOGY

Differential Association Between Statin Exposure and Elevated Levels of Creatine Kinase

¹ Pharmacy Outcomes and Quality Coordinator, Pharmacy Outcomes Research Group, Pharmacy Operations, Kaiser Permanente Medical Care Program, Oakland, CA
² Pharmacoeconomic Pharmacist, Pharmacy Outcomes Research Group, Pharmacy Operations, Kaiser Permanente Medical Care Program, Oakland
³ Chairperson, Chief of Cardiology, Department of Medicine, Division of Cardiology, Kaiser Permanente Medical Center, Santa Clara, CA

Reprints: Dr. Chan, Pharmacy Outcomes Research Group, Pharmacy Operations, Kaiser Permanente Medical Care Program, 1800 Harrison, 13th Fl., Oakland, CA 94612-3429, fax 510/625-3307, jim.chan{at}kp.org

BACKGROUND: Although hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are generally well tolerated, myopathy can be a serious adverse event. The association among different statins, doses, and related risk factors is not well understood.

OBJECTIVE: To determine the prevalence of elevated creatine kinase (CK) levels in patients taking statins, specific doses of these drugs, and other factors. Simvastatin and lovastatin were the drugs of primary interest.

METHODS: In a modified prevalence (cross-sectional) study, prescriptions and laboratory data for 215 191 patients exposed to a statin in 2002 were reviewed. A log-linear Poisson regression model was used to determine the statistical relationship of an elevated CK level to other independent variables.

RESULTS: Prevalence of high elevation of CK levels (ie, n of cases/1000 pts. exposed to statins) was 1.6; prevalence of mild to moderate elevation of CK levels was 6.4. For high elevations, the prevalence ratios were lower for low doses of lovastatin than for high doses of simvastatin. A higher prevalence ratio was associated with elevated serum creatinine (SCr) levels (2.44), exposure to interacting drugs (1.62), male gender (1.48), and evidence of diabetes (1.34). For mild to moderate elevation, a higher prevalence ratio was associated with elevated SCr (1.45), exposure to interacting drugs (1.21), male gender (3.19), age 65 years (1.35), and evidence of diabetes (1.34). Lower prevalence ratios were associated with all doses of lovastatin compared with those of high doses of simvastatin.

CONCLUSIONS: Compared with simvastatin, lovastatin was generally associated with a lower prevalence of high elevation and mild to moderate elevation of CK levels. An elevated SCr level, exposure to interacting drugs, male gender, evidence of diabetes, and age 65 years were associated with higher prevalence ratios.

Key Words: creatine kinase, hydroxymethylglutaryl-coenzyme A reductase inhibitors, myopathy

Published Online, September 13, 2005. www.theannals.com, DOI 10.1345/aph.1G035