An analysis of health plan records of more than one million children and young adults found no association between current use of attention deficit-hyperactivity disorder (ADHD) drugs and an increased risk of serious cardiovascular events, based on study results published Nov. 1 online in the New England Journal of Medicine.
The relationship between the use of ADHD drugs in children and young adults and cardiovascular events such as sudden cardiac death has been controversial. In past years, the FDA has expressed concerns over the safety of ADHD drugs, which prompted an American Heart Association writing group to publish a review in 2008 about cardiovascular monitoring of children receiving ADHD drugs. The recommendations were subsequently amended in 2009.
William O. Cooper, MD, MPH, of the division of general pediatrics at Vanderbilt University School of Medicine in Nashville, Tenn., and colleagues designed a large, retrospective cohort study in an attempt to clarify the issue. Using health plans from Tennessee Medicaid, Washington State Medicaid, the Northern and Southern regions of Kaiser Permanente California and the nationwide private insurer OptumInsight Epidemiology, they obtained records for 1,200,438 children and young adults (mean age, 11.1 years old) who were prescribed medications to treat ADHD between 1986 and 2002. The study had a total follow-up of 2,579,104 person-years, with 373,667 person-years of current use of ADHD drugs.
The study endpoint was one of three serious cardiovascular events: sudden cardiac death, MI or stroke. Their analyses included calculation of hazard ratios for ADHD drug recipients compared with non-ADHD drug users. They also conducted a series of additional analyses to test the findings and study assumptions.
They found that 81 ADHD drug users had a serious cardiovascular event, or 3.1 per 100,000 person-years. Of those, 33 were sudden cardiac deaths (1.3 per 100,000 person-years), nine were acute MIs (0.3 per 100,000 person-years) and 39 were strokes (1.5 per 100,000 person-years).
“Our findings that the use of ADHD drugs was not associated with an increased risk of serious cardiovascular events in children and young adults are consistent with the results of several reports that have appeared since the FDA safety review of adverse-event data for ADHD drugs, although our results differed from the findings of another report,” Cooper and colleagues wrote. “Our study included nearly twice the person-time of the combined person-time in four recent cohort studies and included several provisions to ensure accurate case ascertainment, including a review of medical records and autopsies.”
The authors noted that the low number of adverse cardiac events limited their ability to statistically evaluate individual end points for most individual drugs and analyses for subgroups who may be more vulnerable to the effects of ADHD drugs. For methylphenidate, the most frequently used ADHD drug, they found no increased risk. Given the sparse data for other drugs, though, they wrote that they could not use regression models.
“Although the point estimates of the relative risks for ADHD drugs did not indicate increased risk, the upper limit of the 95 percent confidence interval suggested that a doubling in the risk could not be ruled out,” they concluded. “However, the absolute magnitude of any increased risk would be low.”