Comparison of two methodologies to analyze exposure to statins in an observational study on effectiveness.
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.
Maitland-van der Zee
Anke Hilse
AH
Department of Pharmacoepidemiology & Pharmacotherapy, Utrecht Institute of Pharmaceutical Sciences (UIPS), Utrecht University, Sorbonnelaan 16, P.O. Box 80082, 3508 TB, The Netherlands.
Klungel
Olaf H
OH
Stricker
Bruno H Ch
BH
Verschuren
W M Monique
WM
Witteman
Jacqueline C M
JC
Stijnen
Theo
T
Hofman
Albert
A
Breteler
Monique M B
MM
Leufkens
Hubertus G M
HG
de Boer
Anthonius
A
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
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors