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

Anders Holt; Jarl E Strange; Peter Vibe Rasmussen; Nina Nouhravesh; Sebastian Kinnberg Nielsen; Caroline Sindet-Pedersen; Emil Loldrup Fosbøl; Lars Køber; Christian Torp-Pedersen; Gunnar H Gislason; Patricia McGettigan; Morten Schou; Morten Lamberts

doi:10.1016/j.jacc.2024.03.375

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

Anders Holt^*, Jarl E Strange, Peter Vibe Rasmussen, Nina Nouhravesh, Sebastian Kinnberg Nielsen, Caroline Sindet-Pedersen, Emil Loldrup Fosbøl, Lars Køber, Christian Torp-Pedersen, Gunnar H Gislason, Patricia McGettigan, Morten Schou, Morten Lamberts

^*Corresponding author for this work

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.

Original language	English
Journal	Journal of the American College of Cardiology
Volume	83
Issue number	19
Pages (from-to)	1870-1882
Number of pages	13
ISSN	0735-1097
DOIs	https://doi.org/10.1016/j.jacc.2024.03.375
Publication status	Published - 14 May 2024

Keywords

Humans
Attention Deficit Disorder with Hyperactivity/epidemiology
Female
Male
Adult
Cardiovascular Diseases/epidemiology
Young Adult
Registries
Middle Aged
Follow-Up Studies
Heart Disease Risk Factors
Central Nervous System Stimulants/adverse effects
Time Factors

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10.1016/j.jacc.2024.03.375

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Holt, A., Strange, J. E., Rasmussen, P. V., Nouhravesh, N., Nielsen, S. K., Sindet-Pedersen, C., Fosbøl, E. L., Køber, L., Torp-Pedersen, C., Gislason, G. H., McGettigan, P., Schou, M., & Lamberts, M. (2024). Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults. Journal of the American College of Cardiology, 83(19), 1870-1882. https://doi.org/10.1016/j.jacc.2024.03.375

Holt, A, Strange, JE , Rasmussen, PV , Nouhravesh, N , Nielsen, SK , Sindet-Pedersen, C , Fosbøl, EL , Køber, L , Torp-Pedersen, C , Gislason, GH, McGettigan, P, Schou, M & Lamberts, M 2024, 'Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults', Journal of the American College of Cardiology, vol. 83, no. 19, pp. 1870-1882. https://doi.org/10.1016/j.jacc.2024.03.375

@article{f5bf7084e5a3452d8f163de0148d21ad,

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

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 = "Humans, Attention Deficit Disorder with Hyperactivity/epidemiology, Female, Male, Adult, Cardiovascular Diseases/epidemiology, Young Adult, Registries, Middle Aged, Follow-Up Studies, Heart Disease Risk Factors, Central Nervous System Stimulants/adverse effects, Time Factors",

author = "Anders Holt and Strange, {Jarl E} and Rasmussen, {Peter Vibe} and Nina Nouhravesh and Nielsen, {Sebastian Kinnberg} and Caroline Sindet-Pedersen and Fosb{\o}l, {Emil Loldrup} and Lars K{\o}ber and Christian Torp-Pedersen and Gislason, {Gunnar H} and Patricia McGettigan and Morten Schou and Morten Lamberts",

year = "2024",

month = may,

day = "14",

doi = "10.1016/j.jacc.2024.03.375",

language = "English",

volume = "83",

pages = "1870--1882",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier Inc",

number = "19",

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TY - JOUR

T1 - Long-Term Cardiovascular Risk Associated With Treatment of Attention-Deficit/Hyperactivity Disorder in Adults

AU - Holt, Anders

AU - Strange, Jarl E

AU - Rasmussen, Peter Vibe

AU - Nouhravesh, Nina

AU - Nielsen, Sebastian Kinnberg

AU - Sindet-Pedersen, Caroline

AU - Fosbøl, Emil Loldrup

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

AU - McGettigan, Patricia

AU - Schou, Morten

AU - Lamberts, Morten

PY - 2024/5/14

Y1 - 2024/5/14

N2 - 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.

AB - 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.

KW - Humans

KW - Attention Deficit Disorder with Hyperactivity/epidemiology

KW - Female

KW - Male

KW - Adult

KW - Cardiovascular Diseases/epidemiology

KW - Young Adult

KW - Registries

KW - Middle Aged

KW - Follow-Up Studies

KW - Heart Disease Risk Factors

KW - Central Nervous System Stimulants/adverse effects

KW - Time Factors

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U2 - 10.1016/j.jacc.2024.03.375

DO - 10.1016/j.jacc.2024.03.375

M3 - Journal article

C2 - 38719367

SN - 0735-1097

VL - 83

SP - 1870

EP - 1882

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 19

ER -

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

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