The New England Journal of Medicine, 2011, Vol.365(20), pp.1896-1904
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.) This large study found no increased risk of cardiovascular events in children and young adults using attention deficit–hyperactivity disorder (ADHD) drugs. Although the data are compatible with nearly a doubling of risk, the study was underpowered and the absolute event rate was quite low. Medications that are used to treat attention deficit–hyperactivity disorder (ADHD) are prescribed for more than 2.7 million children in the United States each year1 and have been considered to be relatively safe.2–5 However, reports of adverse events from Canada and the United States that have included cases of sudden death, myocardial infarction, and stroke in conjunction with the use of these drugs have raised concern about their safety.6,7 Although case reports from adverse-event reporting systems can be an important source for identifying medication safety signals, they cannot reliably quantify risk. Thus, there is a compelling need to obtain . . .