title: Adherence to statin therapy and the incidence of ischemic stroke in patients with diabetes.
abstract: OBJECTIVE
  We aimed to quantify for the first time the relationship between statin adherence and ischemic stroke (IS) in patients with diabetes.
  
  
  METHODS
  Using Finnish health registers, we assembled a cohort of 52 868 statin initiators with diabetes in 1995-2006. We conducted a nested case-control analysis matching cases with IS with up to four controls for age, sex, date of statin initiation and follow-up duration. Adjusted rate ratios for IS were estimated with conditional logistic regression. Additional potential confounders were considered with inverse probability weighting and the role of unmeasured confounding using external adjustment. Statin adherence was measured as the proportion of days covered (PDC).
  
  
  RESULTS
  Among 1703 cases and 6799 controls, good adherence to statins (PDC ≥ 80%) was associated with a 23% decreased incidence of IS (95%CI 14-32%) compared with poor adherence (PDC < 80%). This association remained broadly unchanged when stratified by sex, age, history of atherosclerotic cardiovascular disease or IS. There was a dose-response relationship between adherence level and the risk of IS (RR 0.63 [0.53-0.75] for PDC ≥ 80% versus PDC < 20%, P for trend <0.0001). Among patients with good adherence, those initiating with low intensity statin therapy had a 15% lower incidence (95%CI 2-27%) and those initiating with moderate intensity therapy a 29% lower incidence (16-41%) of IS compared with those with poor adherence who initiated with low intensity therapy. Our sensitivity analyses supported the robustness of the results.
  
  
  CONCLUSIONS
  In diabetes, poor statin adherence may considerably increase the risk of IS both in primary and secondary prevention of IS.
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Division of Pharmaceutical Outcomes and Policy, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Public Health, University of Turku, Turku, Finland.
authors.forename: Maarit Jaana
authors.initials: MJ
authors.lastname: Korhonen
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Päivi
authors.initials: P
authors.lastname: Ruokoniemi
authors.affiliation: Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Melbourne, Victoria, Australia.
authors.forename: Jenni
authors.initials: J
authors.lastname: Ilomäki
authors.affiliation: Departments of Medicine and the Florey, University of Melbourne, Melbourne, Victoria, Australia.|Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.
authors.forename: Atte
authors.initials: A
authors.lastname: Meretoja
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Unit of Primary Health Care, Hospital District of Helsinki and Uusimaa, Helsinki, Finland.
authors.forename: Arja
authors.initials: A
authors.lastname: Helin-Salmivaara
authors.affiliation: Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.|Unit of Clinical Pharmacology, Turku University Hospital, Turku, Finland.
authors.forename: Risto
authors.initials: R
authors.lastname: Huupponen
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*; D016022:Case-Control Studies; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000453:epidemiology*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D015994:Incidence; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
keywords: adherence; ischemic stroke; pharmacoepidemiology; statins