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Letter in Pharmacoepidemiology and Drug Safety: Statin-Associated Rhabdomyolysis

This Letter to the Editor appeared in the April 2005 issue of Pharmacoepidemiology and Drug Safety.

Full Citation
Ardati A, Stolley P, Knapp DE, Wolfe SM, Lurie P. Statin-associated rhabdomyolyis (letter). Pharmacoepidemiology and Drug Safety 2005;14:287.

We read with great interest the study of Chang et al. on rhabdomyolysis and statins.1 When our group studied the Food and Drug Administration’s Adverse Event Reporting System database for statin-associated rhabdomyolysis, we did not use a strict CPK cut-off to identify rhabdomyolysis cases the way Chang did. Twenty-eight percent of cases did not include CPK data. Thus, by using clinician-defined cases of rhabdomyolysis as our entry criterion, our study likely includes cases that more closely resemble those encountered by primary practitioners who prescribe the majority of statin medications.

We identified 936 cases of rhabdomyolysis between October 1997 and December 2000, of which noncerivastatin-related cases accounted for 456 (47%). Non-cerivastatin cases had a median peak CPK value of 15 080 IU/L with 38% of cases having peak CPK values ≤10 000 IU/L (the cut-off used by Chang), while the median peak CPK for cerivastatin cases was 35 000 (13%≤10 000 IU/L). Using this larger data set, we also found that the noncerivastatin associated cases had much longer median times to disease onset than the cerivastatin cases (208 vs. 31 days). Like Chang, we found that mortality was higher in the non-cerivastatin group, occurring in 12% of rhabdomyolysis cases compared to 4% of cerivastatin cases.

We also found that 54% of cerivastatin associated cases occurred in the context of concomitant fibrate use. However, when comparing fibrate- and non-fibrate associated cerivastatin cases, we found no difference in time to disease onset, median peak CPK levels, or the rates of hospitalization, death, acute renal failure or dialysis. The clinical picture of toxicity with cerivastatin appears to be largely due to cerivastatin itself.

We conclude that, compared to other statin drugs, cerivastatin-associated rhabdomyolysis is notable for a shorter time to onset, higher median peak CPK levels, more concomitant fibrate use and lower case-fatality percentages. Statin-induced rhabdomyolysis with the currently available statins typically occurs after long periods of event-free use, underscoring the need for active vigilance by clinicians.

Amer Ardati, M.D.
Public Citizen’s Health Research Group

Paul Stolley, M.D.
Public Citizen’s Health Research Group

Deanne E. Knapp, Ph.D.
Public Citizen’s Health Research Group

Sidney M. Wolfe, M.D.
Public Citizen’s Health Research Group

Peter Lurie, M.D., M.P.H.
Public Citizen’s Health Research Group

1. Chang JT, Staffa JA, Parks M, Green L. Rhabdomyolysis with HMG-CoA reductase inhibitors and gemfibrozil combination therapy. Pharmacoepidemiol Drug Safe 2004; 13: 417–426.