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Long-Term CV Risk of ADHD Treatment in Adults
Quick Takes
- In this nationwide cohort study of adult first-time users of ADHD treatment, associations between treatment and elevated 10-year risk of stroke, HF, and a composite CV outcomes were found.
- A dose response in CV risk appears stepwise, with an increase in 10-year risk comparing individuals on higher dosage with lower dosage and prior use.
- No associations with increased risk of ACS were found.
Study Questions:
Is the long-term use of medications used for the treatment of attention-deficit/hyperactivity disorder (ADHD) associated with an increased risk for cardiovascular (CV) outcomes?
Methods:
Data from Danish nationwide registries were used for the present analysis. Adults (≥18 years of age) who initiated ADHD treatment between 1998 and 2020 were grouped by exposure into three groups (prior users, <1 defined daily dose [DDD], and ≥1 DDD per day). Follow-up was initiated 1 year after ADHD initiation among individuals alive and without a history of acute coronary syndromes (ACS), heart failure (HF), or stroke. ADHD medications included methylphenidate, atomoxetine, lisdexamfetamine, dexamfetamine, or modafinil. A matched background population without ADHD (no claimed prescription of ADHD treatment) was created for comparison. Outcomes of interest included ACS, stroke, HF, and a composite of the above outcomes.
Results:
A total of 73,264 adult users of ADHD treatment were identified. Individuals exposed to ADHD treatment were followed for a median of 6.5 years (interquartile range [IQR], 2.7–10 years), leading to 72%, 58%, and 25% of individuals having at least 3, 5, and 10 years of follow-up. At baseline, 26,357 (36%) had discontinued treatment and were categorized as prior users (42% female, median age of 30 [IQR, 23–41] years), 31,211 (43%) were on <1 DDD per day (47% female, median age of 31 [IQR, 24–41] years), and 15,696 (21%) were on ≥1 DDD per day (47% female, median age of 33 [IQR, 25–41] years). Comparing ≥1 DDD per day with prior users, there was an association with an elevated 10-year risk of stroke (risk ratio [RR], 1.2; 95% confidence interval [CI], 1.0–1.5; numbers needed to harm, 258). A similar increased risk was noted for HF (RR, 1.7; 95% CI, 1.3–2.2; numbers needed to harm, 204), and for the composite outcome (RR, 1.3; 95% CI, 1.1–1.5; numbers needed to harm, 116). An association with ACS was not observed (RR, 1.1; 95% CI, 0.8–1.4). Comparisons between ≥1 DDD per day and <1 DDD per day were significant for stroke, HF, and the composite outcome. No association with ACS was noted. Compared to the matched group (without ADHD), an increased risk of CV outcomes was noted, including <1 DDD per day (RR, 1.4; 95% CI, 1.3–1.5) and ≥1 DDD per day (RR, 1.7; 95% CI, 1.5–1.9).
Conclusions:
The authors conclude that possible associations between elevated long-term CV risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.
Perspective:
These observational data from a large national registry suggest the need for additional research on the long-term use of ADHD medications. Comprehensive medication intake by providers should include the use of such medications.
Clinical Topics: Prevention
Keywords: Attention Deficit Disorder with Hyperactivity, Heart Disease Risk Factors, Pharmacoepidemiology
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