Medications for attention-deficit/hyperactivity disorder do not increase the risk of serious cardiovascular events among young and middle-aged adults, according to the results of a retrospective, population-based cohort study published online Dec. 12 in JAMA.
Stimulants such as methylphenidate, amphetamines, and pemoline, as well as the selective norepinephrine reuptake inhibitor atomoxetine, are known to raise heart rate and to increase systolic blood pressure by approximately 2-5 mm Hg and diastolic blood pressure by 1-3 mm Hg. "Although these effects would be expected to slightly increase risk for myocardial infarction, sudden cardiac death, and stroke, clinical trials have not been large enough to assess risk of these events," said Laurel A. Habel, Ph.D., of Kaiser Permanente Northern California, Oakland, and her associates.
Moreover, cardiovascular safety data from pharmacoepidemiologic studies have been "limited and inconsistent" to date, they said.
Dr. Habel and her colleagues examined the relationship between attention-deficit/hyperactivity disorder (ADHD) medications and cardiovascular risk in a large, geographically and sociodemographically diverse cohort of 443,198 adults aged 25-64 years. A total of 150,359 subjects used ADHD medications, including methylphenidate (45%), amphetamines (44%), atomoxetine, (8%), and pemoline (3%).
Medication use was assessed using pharmacy data on filled prescriptions. In addition, the medical records for all potential cases of MI, sudden cardiac death, and stroke were reviewed to verify those events.
There were 1,357 MIs, 296 sudden cardiac deaths, and 575 strokes in 806,182 person-years of follow-up.
The rates of all of these events combined were not significantly different between current users of ADHD medications and nonusers, with a multivariate adjusted rate ratio of 0.83. There also were no significant differences in these rates between current users and subjects who had used ADHD medications in the past but had stopped taking them (rate ratio, 1.03), the investigators said (JAMA 2011 Dec. 12 [doi:10.1001/jama.2011.1830]).
These results remained consistent when each medication was assessed individually, as well as when ischemic and hemorrhagic strokes were examined separately.
To control for potential differences in cardiovascular disease risk between exposed and nonexposed study subjects, the investigators assigned each subject a summary cardiovascular risk score at baseline. After the data were adjusted for these scores, the results were essentially the same: no increase in the risk of CVD events among ADHD medication users vs. nonusers, regardless of the subjects’ baseline CVD risk.
The data also were analyzed according to whether subjects were new to using ADHD medications or were long-term users, and again there was no difference in CVD risk. Rate ratios also remained consistent in all subgroup analyses, including an assessment of CVD risk by subject age.
Information on some important risk factors and on medication dosage was unavailable, so this study, despite its large size, could not completely rule out a "modestly" elevated risk with ADHD medications, the researchers noted.
This study was funded in part by the Agency for Healthcare Research and Quality, the Food and Drug Administration, and the National Institute on Aging. Dr. Habel reported ties to Merck, Takeda, and Sanofi-Aventis, and her associates reported ties to Optuminsight, Merck, GlaxoSmithKline, Novartis, and Abbott. Dr. Shaw reported receiving travel grants from Jannsen-Cilag, maker of Concerta (methylphenidate).