title: Statin-associated rhabdomyolysis: is there a dose-response relationship?
abstract: BACKGROUND
  Statins have a well-established role in prevention of vascular events but are associated with muscle-related adverse events. The dose relationship with these adverse events is unclear. We present an original analysis of Canadian and US case reports of statin-associated rhabdomyolysis with a focus on dose response. A typical clinical case is also summarized.
  
  
  METHODS
  All cases of statin-associated rhabdomyolysis reported to Health Canada's Canadian Vigilance Program and to the US Food and Drug Administration's Adverse Event Reporting System from 2004-2008 were analyzed by severity and dose equivalence. Canadian national statin utilization data from 2002-2007 were used to estimate the dose-related incidence of rhabdomyolysis corrected for levels of utilization.
  
  
  RESULTS
  The clinical case illustrates well the potential severity of statin-induced rhabdomyolysis. Combined Canadian/US data revealed an average of 812 cases of statin-induced rhabdomyolysis reported annually with a mean patient age of 64.4 years (35.5% female). The worst outcomes reported were renal dysfunction in 17.0%, acute renal failure in 19.8%, dialysis in 5.2%, and death in 7.6%. Using 10 mg atorvastatin per day as the reference dose, the odds ratios of rhabdomyolysis were 3.8 (95% CI 2.3-6.6) for 40 mg/day atorvastatin dose equivalent and 11.3 (95% CI 6.4-20.4) for 80 mg/day atorvastatin dose equivalent.
  
  
  CONCLUSIONS
  The results of our adverse drug analysis suggest a dose-response relationship. Given the widespread use of statins, the ability to predict which patients will experience serious muscle-related harm is a research priority.
authors: Division of Clinical Pharmacology and Therapeutics, McMaster University, Hamilton, Ontario, Canada. holbrook@mcmaster.ca
authors: Anne
authors: A
authors: Holbrook
authors: Mitchell
authors: M
authors: Wright
authors: Melani
authors: M
authors: Sung
authors: Christine
authors: C
authors: Ribic
authors: Steven
authors: S
authors: Baker
mesh_terms: D000069059:Atorvastatin; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy*; D005500:Follow-Up Studies; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D012206:Rhabdomyolysis / Q000139:chemically induced*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin