title: Cardiovascular events and death in children exposed and unexposed to ADHD agents.
abstract: OBJECTIVE
  The objective of this study was to compare the rate of severe cardiovascular events and death in children who use attention-deficit/hyperactivity disorder (ADHD) medications versus nonusers.
  
  
  METHODS
  We performed a large cohort study using data from 2 administrative databases. All children aged 3 to 17 years with a prescription for an amphetamine, atomoxetine, or methylphenidate were included and matched with up to 4 nonusers on the basis of data source, gender, state, and age. Cardiovascular events were validated using medical records. Proportional hazards regression was used to calculated hazard ratios.
  
  
  RESULTS
  We identified 241 417 incident users (primary cohort). No statistically significant difference between incident users and nonusers was observed in the rate of validated sudden death or ventricular arrhythmia (hazard ratio: 1.60 [95% confidence interval (CI): 0.19-13.60]) or all-cause death (hazard ratio: 0.76 [95% CI: 0.52-1.12]). None of the strokes identified during exposed time to ADHD medications were validated. No myocardial infarctions were identified in ADHD medication users. No statistically significant difference between prevalent users and nonusers (secondary cohort) was observed (hazard ratios for validated sudden death or ventricular arrhythmia: 1.43 [95% CI: 0.31-6.61]; stroke: 0.89 [95% CI: 0.11-7.11]; stroke/myocardial infarction: 0.72 [95% CI: 0.09-5.57]; and all-cause death: 0.77 [95% CI: 0.56-1.07).
  
  
  CONCLUSIONS
  The rate of cardiovascular events in exposed children was very low and in general no higher than that in unexposed control subjects. Because of the low number of events, we have limited ability to rule out relative increases in rate.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics and Department of Biostatistics and Epidemiology, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104-6021, USA. hennessy@upenn.edu
authors.forename: Hedi
authors.initials: H
authors.lastname: Schelleman
authors.forename: Warren B
authors.initials: WB
authors.lastname: Bilker
authors.forename: Brian L
authors.initials: BL
authors.lastname: Strom
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: Craig
authors.initials: C
authors.lastname: Newcomb
authors.forename: James P
authors.initials: JP
authors.lastname: Guevara
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Daniel
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cziraky
authors.forename: Sean
authors.initials: S
authors.lastname: Hennessy
mesh_terms: D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology; D002423:Cause of Death / Q000639:trends; D000697:Central Nervous System Stimulants / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000697:Central Nervous System Stimulants