New England Journal of Medicine
William O. Cooper, M.D., M.P.H., Laurel A. Habel, Ph.D., Colin M. Sox, M.D., K. Arnold Chan, M.D., Sc.D., Patrick G. Arbogast, Ph.D., T. Craig Cheetham, Pharm.D., Katherine T. Murray, M.D., Virginia P. Quinn, Ph.D., M.P.H., C. Michael Stein, M.B., Ch.B., S. Todd Callahan, M.D., M.P.H., Bruce H. Fireman, M.A., Frank A. Fish, M.D., Howard S. Kirshner, M.D., Anne O’Duffy, M.D., Frederick A. Connell, M.D., M.P.H., and Wayne A. Ray, Ph.D.
N Engl J Med 2011; 365:1896-1904 November 17, 2011
Background
Adverse-event reports from North America have raised concern that the use of drugs for attention deficit–hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events.
Methods
We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology), with 1,200,438 children and young adults between the ages of 2 and 24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health-plan data and vital records, with end points validated by medical-record review. We estimated the relative risk of end points among current users, as compared with nonusers, with hazard ratios from Cox regression models.
Results
Cohort members had 81 serious cardiovascular events (3.1 per 100,000 person-years). Current users of ADHD drugs were not at increased risk for serious cardiovascular events (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85). Risk was not increased for any of the individual end points, or for current users as compared with former users (adjusted hazard ratio, 0.70; 95% CI, 0.29 to 1.72). Alternative analyses addressing several study assumptions also showed no significant association between the use of an ADHD drug and the risk of a study end point.
Conclusions
This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.)
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