title: Impact of a restrictive drug access program on the risk of cardiovascular encounters in children exposed to ADHD medications.
abstract: BACKGROUND
  ADHD medications increase clinical encounters for cardiovascular symptoms. Uncertain are the roles of differences in ADHD medications and restrictive practices by drug programs.
  
  
  METHODS
  We conducted two nested case-control studies. The first was nested within a cohort of children de novo users of methylphenidate, amphetamines or atomoxetine and the second case-control study was nested within a subcohort of de novo amphetamine or atomoxetine users with no cardiovascular events prior to the first dispensing of either drug. The outcome for both studies was the composite of physician visits, emergency room visits or hospitalizations for cardiovascular reasons. Cases were matched on sex, age and date of entry within the cohorts, with up to 10 controls. Patients with an active dispensation of ADHD medications at the index date (and up to 90 days previously) were considered exposed. Conditional logistic regression was used to calculate odd ratios (OR).
  
  
  RESULTS
  The full cohort comprised 38,495 patients. Among these patients, 3595 (9.3%) had no prior cardiovascular events (the subcohort). In the full cohort, an association was demonstrated with exposure to amphetamine and atomoxetine (but not methylphenidate) and the cardiovascular encounter outcomes. When the sub-cohort was analyzed the associations with amphetamine or atomoxetine were no longer evident.
  
  
  CONCLUSIONS
  Reimbursement policies need to be considered when conducting observational studies. Had the analysis been conducted without consideration of these policies the results would have incorrectly identified amphetamine and atomoxetine as important risk factors for cardiovascular encounters.
authors.forename: Jason
authors.initials: J
authors.lastname: Guertin
authors.forename: Jacques
authors.initials: J
authors.lastname: LeLorier
authors.forename: Madeleine
authors.initials: M
authors.lastname: Durand
authors.forename: Robert
authors.initials: R
authors.lastname: Gow
authors.forename: Anne
authors.initials: A
authors.lastname: Holbrook
authors.forename: Mitchell
authors.initials: M
authors.lastname: Levine
mesh_terms: D000293:Adolescent; D000662:Amphetamines / Q000009:adverse effects; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis / Q000188:drug therapy* / Q000191:economics / Q000523:psychology; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000175:diagnosis / Q000191:economics / Q000628:therapy; D016022:Case-Control Studies; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000191:economics; D002648:Child; D016527:Drug Costs; D004636:Emergency Service, Hospital; D005260:Female; D006297:Health Services Accessibility / Q000191:economics; D006760:Hospitalization; D006801:Humans; D007349:Insurance, Health, Reimbursement; D007356:Insurance, Pharmaceutical Services; D016015:Logistic Models; D008297:Male; D008774:Methylphenidate / Q000009:adverse effects; D016017:Odds Ratio; D009819:Office Visits; D015397:Program Evaluation; D011437:Propylamines / Q000009:adverse effects; D011792:Quebec; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride