title: Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults.
abstract: OBJECTIVE
  To compare the incidence rates of serious cardiovascular events in adult initiators of amphetamines or atomoxetine to rates in non-users.
  
  
  METHODS
  This was a retrospective cohort study of new amphetamines (n=38,586) or atomoxetine (n=20,995) users. Each medication user was matched to up to four non-users on age, gender, data source, and state (n=238,183). The following events were primary outcomes of interest 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, 4) a composite endpoint of stroke or myocardial infarction. Cox proportional hazard regression was used to calculate propensity-adjusted hazard ratios for amphetamines versus matched non-users and atomoxetine versus matched non-users, with intracluster dependence within matched sets accounted for using a robust sandwich estimator.
  
  
  RESULTS
  The propensity-score adjusted hazard ratio for amphetamines use versus non-use was 1.18 (95% CI: 0.55-2.54) for sudden death/ventricular arrhythmia, 0.80 (95% CI: 0.44-1.47) for stroke, 0.75 (95% CI: 0.42-1.35) for myocardial infarction, and 0.78 (95% CI: 0.51-1.19) for stroke/myocardial infarction. The propensity-score adjusted hazard ratio for atomoxetine use versus non-use was 0.41 (95% CI: 0.10-1.75) for sudden death/ventricular arrhythmia, 1.30 (95% CI: 0.52-3.29) for stroke, 0.56 (95% CI: 0.16-2.00) for myocardial infarction, and 0.92 (95% CI: 0.44-1.92) for stroke/myocardial infarction.
  
  
  CONCLUSIONS
  Initiation of amphetamines or atomoxetine was not associated with an elevated risk of serious cardiovascular events. However, some of the confidence intervals do not exclude modest elevated risks, e.g. for sudden death/ventricular arrhythmia.
authors: Center for Clinical Epidemiology and Biostatistics, and Department of Biostatistics & Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors: Hedi
authors: H
authors: Schelleman
authors: Warren B
authors: WB
authors: Bilker
authors: Stephen E
authors: SE
authors: Kimmel
authors: Gregory W
authors: GW
authors: Daniel
authors: Craig
authors: C
authors: Newcomb
authors: James P
authors: JP
authors: Guevara
authors: Mark J
authors: MJ
authors: Cziraky
authors: Brian L
authors: BL
authors: Strom
authors: Sean
authors: S
authors: Hennessy
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D000662:Amphetamines / Q000008:administration & dosage / Q000009:adverse effects*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology; D000069445:Atomoxetine Hydrochloride; D018376:Cardiovascular Abnormalities / Q000139:chemically induced* / Q000503:physiopathology; D003645:Death, Sudden / Q000473:pathology; D064420:Drug-Related Side Effects and Adverse Reactions / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000139:chemically induced / Q000503:physiopathology; D016016:Proportional Hazards Models; D011437:Propylamines / Q000008:administration & dosage / Q000009:adverse effects*; D020521:Stroke / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000662:Amphetamines; D011437:Propylamines; D000069445:Atomoxetine Hydrochloride
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