November 1, 2011 — Attention-deficit/hyperactivity disorder (ADHD) medications do not increase the risk for serious cardiovascular events, new research shows.
A retrospective cohort study of more than 1 million children and young adults found no significant differences in serious cardiac episodes among those who did not use ADHD medications, current users, and former users. In addition, only 3.1 serious cardiovascular events were found per 100,000 person-years.
"We feel that this study offers some reassurance that...there doesn't appear to be an increased risk for sudden death, heart attack, or stroke in those that use these medications," lead investigator William O. Cooper, MD, MPH, professor of pediatrics and preventive medicine at Vanderbilt University in Nashville, Tennessee, told Medscape Medical News.
"These events are fortunately really rare in children. So even though we looked at 1.2 million young people, there was some limit to the study power. Still, the absolute magnitude of any possible increased risk would be really low," Dr. Cooper added.
The study was published online November 1 in the New England Journal of Medicine and funded by the Agency for Healthcare Research and Quality (AHRQ) and by the US Food and Drug Administration (FDA).
In a statement to Medscape Medical News, the FDA said that it will continue to recommend that clinicians prescribe these medications "according to the professional prescribing label."
"A small to modest increase in risk cannot be excluded. Healthcare professionals should take special note that stimulant products and atomoxetine should generally not be used in patients with serious heart problems, or for whom an increase in blood pressure or heart rate would be problematic," said Sandy Walsh, from the FDA Office of Public Affairs.
"Patients treated with ADHD medications should be periodically monitored for changes in heart rate or blood pressure [and] should continue to use their medicine for the treatment of ADHD as prescribed by their healthcare professional."
According to the investigators, 2.7 million American children are prescribed ADHD medications each year.
They note that although previous research from the United States and Canada has linked cases of cardiovascular events with these medications, case reports "cannot reliably quantify risk."
Still, on the basis of concerns raised by these findings, in 2008 the American Heart Association recommended that "it is reasonable" to perform electrocardiography in pediatric patients before prescribing ADHD drugs.
"There's been a lot of confusion for families and for providers about the safety of these medicines. So we set out to do a study that was sufficiently large and sufficiently well-designed to address these issues as carefully as possible," said Dr. Cooper.
A recent, large observational study, published in May 2011 in Pediatrics and reported by Medscape Medical News at that time, also found no significant increase in cardiac events due to use of ADHD medications. However, it was funded by Shire — a manufacturer of ADHD drugs.
In the current study, computerized records dating from 1986 to 2005 were evaluated for 1,200,438 people between ages 2 and 24 years (mean age, 11.1 years; 71% male) from 4 large health plans: Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology. The mean duration of follow-up was 2.1 years.
This represented "2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs," the investigators note.
ADHD medications used included methylphenidate, dexmethylphenidate, dextroamphetamines, amphetamine salts, atomoxetine, and pemoline.
The primary outcome was a serious cardiovascular event by any of the participants (current ADHD medication users, past users, and nonusers). The types of events examined included sudden cardiac death, acute myocardial infarction, or stroke.
First of 3 Studies
Results showed that 81 serious cardiovascular events were experienced by the study population, including 33 sudden cardiac deaths, 39 strokes, and 9 acute myocardial infarctions.
The adjusted rate of serious cardiac events was not significantly increased for current users of ADHD medications compared with the nonusers (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.31 - 1.85) or for former users vs nonusers (HR, 1.03; 95% CI, 0.57 - 1.89).
In addition, there was no increased risk for cardiovascular events when current users were compared with former users (HR, 0.70; 95% CI, 0.29 - 1.72) and no increased risk for any of the individual events.
Finally, no increased risk was found for the specific use of methylphenidate (HR, 0.96; 95% CI, 0.31 - 2.97), "the most frequently used ADHD drug."
Still, Dr. Cooper said that the families of every child and young person being considered for these medications should work with their healthcare provider to carefully decide what the risks and benefits are, especially for those with serious chronic health conditions.
The FDA reports that this is the first of 3 "separate but related studies" that it is co-sponsoring with AHRQ to evaluate the potential risk for serious cardiovascular events after the use of ADHD medications. The remaining 2 studies will focus on adults only.
"I think a great next step would be for people that think about policies related to screenings of children who use these medications to hopefully use this study, along with others, to reach a decision on the best recommendations," said Dr. Cooper.
"In other words, we hope this study provides important information to guide some of those policy decisions."
"This is a very important study," Lenard A. Adler, MD, professor of psychiatry and child and adolescent psychiatry at New York University Langone Medical Center, told Medscape Medical News.
"Cardiovascular events in children treated with similar medication have been reported over time. Although these events are dramatic and serious, there have been few large-scale studies that have been able to use comparison groups to examine whether or not these risks are greater than what is seen in the general population," he added.
Dr. Adler, who was not involved in the study, said that its most important point is that incidence did not differ between patients who were and those who were not exposed to psychostimulants.
"This doesn't mean that individuals taking stimulant medications for ADHD don't need to be monitored. But there's some comfort in these findings," he said.
He noted that clinical recommendations currently vary in regards to this issue.
"Right now we have some guidelines from the American Heart Association, from the American Academy of Child and Adolescent Psychiatry, and from the American Academy of Pediatrics. And there's no consensus among them. The hope is that this study's findings will contribute to establishing consensus among the guidelines to help parents and also practitioners."
Dr. Adler added that the American Professional Society of ADHD and Related Disorders (APSARD), of which he is past president, will hold its annual meeting November 19 in Philadelphia. One of the sessions scheduled for the APSARD meeting is a discussion on cardiovascular risks of stimulant medications — and will include a presentation of this study.
"Overall, I think clinicians should tell families that ADHD is a significant disorder that needs to be treated. And there needs to be a discussion of the potential risks and benefits of all medications considered, especially when treating children," he concluded.
The study was supported by the FDA and by AHRQ. A full list of the study authors' financial relationships can be found in the original article. Dr. Adler reported that he has done research for and consulted for Shire, Eli Lilly, and a variety of other companies that manufacture ADHD products and received royalty payments from New York University for the licensing of ADHD scales. "However, none of those were in conflict with this study," he said.
N Engl J Med. Published online November 1, 2011.
Medscape Medical News © 2011 WebMD, LLC
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Cite this: No Evidence ADHD Meds Increase Cardiovascular Risk - Medscape - Nov 01, 2011.