According to results of a population-based epidemiological study that evaluated the use of the diagnostic code for the statin-complication rhabdomyolysis as a method of estimating the incidence of statin-related rhabdomyolysis and myopathy, the ICD-9 code for rhabdomyolysis is nonspecific for this adverse drug reaction.
The resulting misclassification markedly attenuated the estimated RR for high- vs. low-dose, James S. Floyd, MD, MS, and colleagues wrote in a research letter published in The Journal of the American Medical Association. The diagnostic code for statin-complication rhabdomyolysis was introduced in 2006, according to the authors.
“Studies of rare adverse drug reactions are difficult because they require large numbers of exposed persons to identify an adequate number of cases. Spontaneous adverse event reports have been used to identify cases of rhabdomyolysis, a rare but serious complication of statin use. A complex algorithm based on administrative data also has been used to identify cases of rhabdomyolysis and myopathy among enrollees of several large health plans,” Floyd, of the University of Washington, Seattle, and colleagues wrote.
The study used computerized pharmacy data from all enrollees of Group Health Cooperative from 2006 to 2010. Statin-related rhabdomyolysis was defined as muscle symptoms with a peak creatine kinase level 10 or more times the upper limit of normal, and statin-related myopathy was defined as symptoms with a peak creatine kinase level five to 10 times the upper limit of normal, in the absence of another etiology, according to the research letter.
Of 292 statin users who had an ICD-9 code for rhabdomyolysis, the researchers validated 22 cases of statin-related rhabdomyolysis. They calculated a positive predictive value of 7.5%. Through other methods, seven additional cases of rhabdomyolysis were identified (sensitivity of 76%). Other than statin use, common etiologies for rhabdomyolysis included prolonged immobility, arterial ischemia, recent surgery and severe infection.
Overall, 90% of the 29 validated cases of statin-related rhabdomyolysis were hospitalized, and 29% had at least a doubling of serum creatinine level. None of the patients died.
The median peak creatine kinase level of the patients studied was 7,450 U/L (range, 1,477 U/L to 150,510 U/L).
Compared with other statins
, the incidence rate ratio (IRR) for simvastatin was 2.61 (95% CI, 1.03-7.84) using validated cases compared with 1.03 (95% CI, 0.8-1.34) using the ICD-9 code for rhabdomyolysis, according to the letter. When the researchers examined dose, the IRR for simvastatin >80 mg per day was 12.2 (95% CI, 3.6-52.3) compared with lower doses of 20 mg to 39 mg per day using validated cases vs. 1.77 (95% CI, 1.05-2.88) using the ICD-9 code for rhabdomyolysis.
The researchers said these results confirm that data from the SEARCH trial, conducted by Armitage and colleagues, revealed an increased risk for rhabdomyolysis and myopathy in patients prescribed to high-dose simvastatin and, subsequently, prompted the FDA to issue a warning about the use of high-dose simvastatin.
For more information:
Disclosure: Dr. Floyd reports no relevant financial disclosures. Bruce M. Psaty, MD, PhD, reports serving on a data and safety monitoring board for the clinical trial of a device funded by Zoll and was on a steering committee for the Yale Open Data Access Project funded by Medtronic.