title: Comparison of two methodologies to analyze exposure to statins in an observational study on effectiveness.
abstract: OBJECTIVE
  Estimates of efficacy of drugs from clinical trials may differ from estimates in observational studies. To obtain valid results, the definition of exposure in an observational study is critical. The objective of our study was to compare different exposure definitions for assessing the effectiveness of statins.
  
  
  METHODS
  The study was performed in the Rotterdam Study, a population-based cohort study that included 7983 subjects of > or =55 years of age. We selected 3806 subjects who received antihyperlipidemic drug treatment (n=179) or had a total cholesterol > or =6.5 mmol/L at baseline. We conducted analyses with two different exposure definitions.
  
  
  RESULTS
  Treatment with statins was assessed at baseline. The adjusted relative risk (RR) of myocardial infarction (MI) and stroke was 0.75 (95% confidence interval [CI] 0.41-1.37) and of total mortality was 1.34 (95% CI 0.66-2.74) in subjects treated with statins. We used pharmacy data, which give insight into drug use on a continuous basis. The adjusted RR of MI and stroke after 2 years of cumulative treatment was 0.63 (95% CI 0.34-1.15) and of total mortality was 0.91 (95% CI 0.59-1.39).
  
  
  CONCLUSIONS
  Our results suggest that use of a time-dependent exposure definition is more accurate because estimates of effectiveness were more in agreement with results from randomized controlled trials of statin treatment.
authors.affiliation: Department of Pharmacoepidemiology & Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Sorbonnelaan 16, P.O. Box 80082, 3508 TB, The Netherlands.
authors.forename: Anke Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
authors.forename: W M Monique
authors.initials: WM
authors.lastname: Verschuren
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Theo
authors.initials: T
authors.lastname: Stijnen
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Monique M B
authors.initials: MM
authors.lastname: Breteler
authors.forename: Hubertus G M
authors.initials: HG
authors.lastname: Leufkens
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
mesh_terms: D000368:Aged; D004334:Drug Administration Schedule; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000517:prevention & control*; D009426:Netherlands / Q000453:epidemiology; D020521:Stroke / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors