title: Myopathy Associated With HMG-CoA Reductase Inhibitors (Statins): A Series of 10 Patients and Review of the Literature.
abstract: OBJECTIVE
  To examine the clinical profile of patients with myotoxicity due to HMG-CoA reductase inhibitors and the pathological features in the biopsies.
  
  
  METHODS
  All patients receiving HMG-CoA reductase inhibitors who underwent muscle biopsy at the State Neuropathology Service, Melbourne, from October 2000 to September 2001 were identified, and clinical questionnaires were completed by the referring doctor.
  
  
  RESULTS
  Ten patients, including 4 males and 6 females, aged 50 to 76 years (median, 69.5 y), were identified. Six patients were diabetic and one was severely hypothyroid. Statins included simvastatin in 5, atorvastatin in 4, and cerivastatin in 1. Six patients had either a recent doubling in dosage of statin or change to another statin. Six patients were also taking one or more drugs with known interaction with HMG-CoA reductase inhibitors (gemfibrozil, ketoconazole, calcium channel antagonists, dothiepin, celecoxib, amiodarone). All patients had weakness, 8 had myalgias, and 3 had myoglobinuria. Peak creatine kinase (CK) elevation ranged from 1100 to 160,000 U/L (median, 16,000 U/L). Following cessation of statins, resolution of symptoms and normalization of CK levels were noted in all within a few months. All muscle biopsies showed necrotizing myopathy with minimal inflammation in 4 (40%). Histochemical studies did not suggest mitochondrial cytopathy.
  
  
  CONCLUSIONS
  Myotoxicity due to HMG-CoA reductase inhibitors commonly occurs in patients taking concomitant medication known to interact with metabolism of these agents, such as gemfibrozil or ketoconazole, or with an increase in dose. In addition, elderly patients with obesity, diabetes mellitus, and hypothyroidism appear to be at increased risk of developing myotoxicity.
authors.affiliation: From the *Department of Anatomical Pathology, St. Vincent's Hospital, Melbourne, Victoria, Australia; and the daggerState Neuropathology Service, Department of Pathology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: McKelvie
authors.forename: Xenia
authors.initials: X
authors.lastname: Dennett