Original ArticleHealth plan administrative databases can efficiently identify serious myopathy and rhabdomyolysis
Introduction
Serious myopathy and rhabdomyolysis are muscle-related adverse events that have been reported for a number of drugs, most notably lipid-lowering drugs, including statins and fibrates [1], [2], [3], [4]. Clinically important myopathy and rhabdomyolysis are generally defined by muscle symptoms (e.g., pain, fatigue, or weakness) with creatine kinase (CK) elevations greater than 10 times the upper limit of normal (ULN) [1], [2], [3]. Rhabdomyolysis is often associated with myoglobinuria, myoglobinemia, and end organ damage (e.g., acute renal failure) and may be fatal.
Data on the incidence of rhabdomyolysis among users of lipid-lowering drugs are limited and are based largely on data from spontaneous reporting systems and clinical trials [1], [4], [5]. Administrative databases may be useful to identify potential adverse events, such as serious myopathy or rhabdomyolysis, for assessment of the incidence and risk factors for the disease. However, the International Classification of Diseases, 9th revision (ICD-9-CM) code for rhabdomyolysis is nonspecific, and a number of different muscle-related diagnoses, in addition to diagnoses related to end organ damage, may be suggestive of serious myopathy and rhabdomyolysis. Thus, assessment of the validity of diagnostic criteria for identification of rhabdomyolysis is warranted. We evaluated the positive predictive values (PPVs) of specific criteria based upon ICD-9-CM codes to assess the utility of using automated administrative databases to identify cases of serious myopathy and rhabdomyolysis.
Section snippets
Methods
We conducted a retrospective study among patients enrolled in 11 geographically dispersed managed care organizations (five in the Midwest, three in the Northeast, two in the Southeast, and one in the West) that included independent practice associations and staff and group practice models. Each of the organizations maintains computerized databases of pharmacy dispensings, inpatient and outpatient diagnoses and procedures, and enrollment and demographic data.
Institutional Review Board (IRB)
Results
Among 206,732 new statin users and 15,485 new fibrate users, 194 hospitalizations met the criteria for chart review. Of these hospitalizations, 174 charts (90%) were reviewed and abstracted. The mean age of patients at hospitalization was 64 years (range 32–86), and 56% were female. The gender and age distributions of the 20 patients whose records could not be reviewed were similar to those of patients whose records were reviewed.
Thirty-one cases of clinically important myopathy or
Discussion
Our results suggest that administrative databases may be useful for signal detection of drug exposures potentially associated with rhabdomyolysis. Given that the large majority of cases were identified with criteria that included a discharge diagnosis of myoglobinuria (criterion 1) or other disorder of the muscle (using criteria 2, 3, and 4) and that the overall PPV using only these criteria was 74%, investigators with limited resources might choose to restrict case identification using these
Acknowledgments
This work was supported by grants FD-U-001641, FD-U-001643, and FD-U-002067 from the US Food and Drug Administration. We are grateful to Rachel Kasper, Nicole Boudreau, Claire Canning, Kristi Paulsen, and Margaret Burgess for their technical support. The views expressed herein are those of the authors and not necessarily those of the Food and Drug Administration.
References (7)
- et al.
Statin-associated myopathy
JAMA
(2003) Lipid-lowering agents and myopathy
Curr Opin Rheumatol
(2002)- et al.
Risk for myopathy with statin therapy in high-risk patients
Arch Intern Med
(2003)
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