title: Simvastatin dose and risk of rhabdomyolysis: nested case-control study based on national health and drug dispensing data.
abstract: BACKGROUND
  Two randomised controlled trials have found a higher risk of rhabdomyolysis in users of 80 mg versus 20 mg simvastatin, but there is very limited information about the risk associated with other doses. We undertook a nested case-control study, using routinely collected national health and drug dispensing data, to estimate the relative and absolute risks of rhabdomyolysis resulting in hospital admission or death according to simvastatin dose.
  
  
  RESULTS
  The underlying study cohort comprised all patients (n=313,552) who initiated a new episode of simvastatin use in New Zealand between 1 May 2005 and 31 December 2009. Cases (n=29) were patients with a diagnosis of rhabdomyolysis after cohort entry, confirmed by hospital discharge letter or death records. Ten controls, matched by year of birth and sex, were randomly selected from the study cohort using risk set sampling. Current users of 40 mg simvastatin daily were about five times as likely to develop rhabdomyolysis as those taking 20mg; the adjusted odds ratio was 5.3 (95% CI 1.9-15.0). The absolute excess risk of rhabdomyolysis associated with the use of 40 mg versus 20mg was about 10 per 100,000 person-years; the crude incidence rates were 11.5 (95% CI 7.1-17.5) and 2.1 (95% CI 0.7-4.8) per 100,000 person-years respectively.
  
  
  CONCLUSIONS
  These findings provide reassurance that the absolute risk of rhabdomyolysis in a general population of simvastatin users is very low. Nonetheless, they also raise questions about the optimal simvastatin regimen to maximise cardiovascular benefits and minimise the risk of serious muscle injury.
authors.affiliation: Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand. Electronic address: lianne.parkin@otago.ac.nz.
authors.forename: Lianne
authors.initials: L
authors.lastname: Parkin
authors.affiliation: Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Paul
authors.affiliation: Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand.
authors.forename: G Peter
authors.initials: GP
authors.lastname: Herbison
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000453:epidemiology*; D018570:Risk Assessment; D019821:Simvastatin / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: Case–control studies; Nested; Odds ratio; Rhabdomyolysis; Risk; Statins