No Increased CVD Event Risk With ADHD Meds in Kids With Autism

CHICAGO ― There appears to be no increased risk for serious cardiovascular events associated with stimulant medication use by children and adolescents with autism spectrum disorder (ASD), according to new research.

In an analysis of more than 300,000 ASD patients, the incidence rate of serious cardiac events was approximately 0.01%, a rate that was statistically comparable for ASD patients who were taking stimulant medications and their counterparts who were not taking such medications.

"Even after controlling for a host of variables that we know are related to cardiac events, we still found no difference between the patients who were taking ADHD [attention-deficit/hyperactivity disorder] medications and those who weren't," Richard Houghton, MSc, told Medscape Medical News. "So no matter what we do, all our analyses align with the null hypothesis that there's no difference between cases and matched controls."

Houghton said the study is "novel" in that it's the first such investigation conducted solely in children and adolescents with ASD.

The findings were presented here at the American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting.

A More Vulnerable Population?

Stimulant medications are commonly used in the treatment of children and adolescents with ASD. A recent study showed that approximately 34% of children and 42% of adolescents with ASD might be taking ADHD medication.

ADHD medications have been shown to increase mean blood pressure, heart rate, and QT interval in children, adolescents, and adults and have been tied to serious cardiovascular events in case reports. The US Food and Drug Administration (FDA) issued a class-specific warning regarding the potential for serious cardiovascular risks associated with use of stimulants in 2006.

However, research conducted since the 2006 FDA warning suggests that the CVD risk associated with these medications is slim to none. As reported by Medscape Medical News, a 2011 study of more than 1 million children and young adults that was published in the New England Journal of Medicine showed there was no increased cardiovascular risk tied to ADHD medications.

"On the whole, the literature has been squarely aligned with respect to risk of serious cardiovascular events among the entire population of children and adolescents receiving or not receiving ADHD medications," said Houghton, a principal real-world data scientist and employee of F. Hoffmann-La Roche Ltd, which funded the study.

"Nevertheless, we wondered whether the incidence would be higher within the ASD cohort, because they may either have a higher level of other psychiatric comorbidities or simply be more vulnerable," he added.

As part of the nested case-control study, the researchers examined the Market Scan database for insurance claims data for the period 2000 to 2016. The final cohort included individuals aged 3 to 18 years for whom two or more prescriptions for ASD medications had been filled, who had not been diagnosed with Rett syndrome, and who had no previous history of a cardiovascular event.

Serious cardiovascular events included the first signs of either stroke, myocardial infarction, ventricular arrhythmia, or cardiac arrest. Each case patient was matched with 10 control persons on the basis of calendar time, age, sex, and insurance type. The researchers analyzed each case patient to determine whether he or she had a current prescription for stimulants and/or atomoxetine, which was the main exposure definition.

The analysis identified 326,221 individuals (80.4% male) with ASD. Of these, 48 (0.01%) were found to have had a serious cardiovascular event. The incidence rate of cardiovascular events in the ASD cohort was 5.62 per 100,000 patient-years (95% confidence interval [CI], 4.23 – 7.45).

All case patients were compared to matched control persons. The control group consisted of 480 children and youth with ASD who had not received ADHD medications. The mean age of patients in the combined cohort was 12.5 ± 4.4 years; 79.2% were male.

The analysis showed that only 6 of the 48 patients who experienced a serious cardiovascular event (12.5%) were currently exposed to ADHD medication, compared with 106 of the 480 control patients (22.1%). This, the researchers said, translated to no association between the occurrence of cardiovascular events and ADHD medication use in the crude matched analysis (odds ratio [OR] = 0.49; 95% CI, 0.20 – 1.20).

"Fortunately," Houghton said, "the incidence rate was pretty low."

Moreover, the ORs for stroke (0.52; 95% CI, 0.14 – 1.84) and serious cardiac arrhythmia (0.62; 95% CI, 0.17 – 2.24) were similar to the composite score in the crude matched analysis.

After adjusting for all covariates using both a propensity score approach (OR, 0.71; 95% CI, 0.28 – 1.83) and an adjusted logistic regression model (OR, 1.20; 95% CI, 0.33 – 4.41), the results were similar.

"We went into the study knowing that despite starting with a massive dataset, the eventual event rates would be quite low. Our event rates are pretty much on par with what's been seen in the literature," said Houghton.

Houghton was quick to point out that despite the size of the database and the strength of the findings, the study does not definitively demonstrate the safety of ADHD medication for young people with ASD.

"Maybe the people that had a cardiovascular event were different in some way to the entire general cohort of 300,000, so one thing that's really important is not to simply generalize these findings," he said.

"The interpretation is that within a group of children that was somehow at risk, these are the ones that ended up having a cardiovascular event," he added. "And within that group of kids, this study says there was no incremental effect of the ADHD medication," Houghton added.

Confirmatory Findings

Commenting on the findings for Medscape Medical News, William Cooper, MD, MPH, noted that although the study is small, its findings are very similar to those of previous studies of ADHD medication safety.

"For children and their families with ASD who may benefit from these medications, the study could provide additional information as they consider the risks and benefits of their use," said Cooper, professor of pediatrics and health policy at Vanderbilt University Medical Center in Nashville, Tennessee.

Also commenting, Ryan S. Sultan, MD, noted that concerns have long existed regarding the association between the use of stimulant medications and cardiovascular events.

"These findings from a large national dataset support past research that ADHD medications do not increase the risk of cardiovascular events in otherwise healthy individuals," said Sultan, assistant professor of clinical psychiatry at Columbia University Medical Center in New York City.

"Previous work has concentrated on the entire population of ADHD youth. It is comforting to know that these medications can continue to be recommended as first-line treatments for ADHD in youth with autism," Sultan added.

The study was funded by F. Hoffman–La Roche Ltd. Houghton is an employee of F. Hoffman–La Roche Ltd. Cooper and Sultan have disclosed no relevant financial relationships.

American Academy of Child & Adolescent Psychiatry (AACAP) 66th Annual Meeting: Abstract 1.28, presented October 16, 2019.

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