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. 2024 May 14;83(19):1870-1882.
doi: 10.1016/j.jacc.2024.03.375.

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults

Anders Holt  1 , Jarl E Strange  2 , Peter Vibe Rasmussen  3 , Nina Nouhravesh  3 , Sebastian Kinnberg Nielsen  3 , Caroline Sindet-Pedersen  3 , Emil Loldrup Fosbøl  4 , Lars Køber  4 , Christian Torp-Pedersen  5 , Gunnar H Gislason  6 , Patricia McGettigan  7 , Morten Schou  8 , Morten Lamberts  8
Affiliations

Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults

Anders Holt et al. J Am Coll Cardiol. .

Abstract

Background: Incrementing numbers of patients treated for attention-deficit/hyperactivity disorder (ADHD) call for scrutiny concerning long-term drug-safety.

Objectives: This study aims to investigate associations between long-term use of ADHD treatment and cardiovascular outcomes.

Methods: Using nationwide registers, adult patients first-time initiated on ADHD treatment between 1998 and 2020 were identified. Exposure groups were prior users, <1 defined daily dose (DDD) per day, ≥1 DDD per day determined at start of follow-up, and 1 year after patients' first claimed prescription. Outcomes were acute coronary syndromes, stroke, heart failure, and a composite of the above.

Results: At start of follow-up, 26,357, 31,211, and 15,696 individuals were correspondingly categorized as prior users (42% female, median age: 30 years [Q1-Q3: 23-41 years]), <1 DDD per day (47% female, median age: 31 years [Q1-Q3: 24-41 years]), and ≥1 DDD per day (47% female, median age: 33 years [Q1-Q3: 25-41 years]), respectively. Comparing ≥1 DDD per day with prior users, elevated standardized 10-year absolute risk of stroke (2.1% [95% CI: 1.8%-2.4%] vs 1.7% [95% CI: 1.5%-1.9%]), heart failure (1.2% [95% CI: 0.9%-1.4%] vs 0.7% [95% CI: 0.6%-0.8%]), and the composite outcome (3.9% [95% CI: 3.4%-4.3%] vs 3.0% [95% CI: 2.8 %-3.2%]) was found-with corresponding risk ratios of 1.2 (95% CI: 1.0-1.5), 1.7 (95% CI: 1.3-2.2), and 1.3 (95% CI: 1.1-1.5). No apparent associations were found for acute coronary syndrome (1.0% [95% CI: 0.8%-1.2%] vs 0.9% [95% CI: 0.8%-1.0%]).

Conclusions: Possible associations between elevated long-term cardiovascular risk and increasing dosage of ADHD treatment use in a young patient group should warrant further investigation.

Keywords: acute coronary syndrome; attention-deficit/hyperactivity disorder; attention-deficit/hyperactivity disorder treatment; drug-safety; heart failure; pharmacoepidemiology; stroke.

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Conflict of interest statement

Funding Support and Author Disclosures This study has been funded by external, independent grants from “IMK Almene Fond” (J. nr. 30206-383), “Helsefonden” (20-B-0035) “Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond” (J 167/1), “Marie og M.B. Richters Fond” (J. nr. 2020-0379), and “Dagmar Marshalls Fond.” Dr Fosbøl has received grants from the Novo Nordisk Foundation for research in valvular heart disease, unrelated to this study. Dr Køber has received speaker fees from Novo, AstraZeneca, Novartis, and Boehringer, unrelated to this study. Dr Torp-Pedersen has received grants from Novo and Bayer, unrelated to this study. Dr Schou has received speaker fees from Novartis, Boehringer Ingelheim, Bayer, Novo, and AstraZeneca, unrelated to this study. Dr Lamberts has received grants from Karen Elise Jensen Fonden, Danish Heart Foundation, Bayer, and BMS; has received speaker fees from BMS/Pfizer, Bayer, AstraZeneca, MSD, and Merck; and has had advisory board positions with BMS/Pfizer, Bayer, and Mundipharma, unrelated to this study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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