ADHD Medications and Risk of Serious Cardiovascular Events in Young and Middle-Aged Adults

Study Questions:

What is the association between current use of medications prescribed primarily to treat attention deficit hyperactivity disorder (ADHD) and increased risk of serious cardiovascular events in young and middle-aged adults?

Methods:

This was a retrospective, population-based cohort study using electronic health care records from four study sites (Optum Insight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at one site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults ages 25-64 years, with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to two nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). The main outcome measures were serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias.

Results:

During 806,182 person-years of follow-up (median, 1.3 years per person), 1,357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1,000 person-years of 1.34 (95% confidence interval [CI], 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use versus nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use versus remote use was 1.03 (95% CI, 0.86-1.24); for new use versus remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1,000 person-years at ages 25-44 years and 0.77 events per 1,000 person-years at ages 45-64 years.

Conclusions:

The authors concluded that current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events.

Perspective:

In this population-based cohort of young and middle-aged adults, including more than 150,000 users of ADHD medications identified through filled prescriptions, the investigators found no evidence of an increased risk of MI, SCD, or stroke associated with current use compared with nonuse or remote use of ADHD medications. Furthermore, the study provides no evidence to support routine obtaining of electrocardiograms before starting treatment, since this recommendation was driven by concerns about serious cardiovascular events with these drugs. Based on this study, physicians can now use solid evidence to address concerns about cardiovascular risk while discussing with patients the risks and benefits of ADHD medications.

Keywords: Attention Deficit Disorder with Hyperactivity, Outcome Assessment (Health Care), Myocardial Infarction, Stroke, Follow-Up Studies, Electrocardiography, Tennessee, Incidence, Propylamines, Death, California, Cardiology, Cardiovascular Diseases, Risk Assessment, United States


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