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Risk of cardiovascular diseases associated with medications used in Attention-Deficit/Hyperactivity Disorder: a aystematic review and meta-analysis

Risk of cardiovascular diseases associated with medications used in Attention-Deficit/Hyperactivity Disorder: a aystematic review and meta-analysis
Risk of cardiovascular diseases associated with medications used in Attention-Deficit/Hyperactivity Disorder: a aystematic review and meta-analysis

Importance: use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.

Objective: to provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).

Data sources: PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.

Study selection: observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.

Data extraction and synthesis: independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline.

Main outcomes and measures: the outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.

Results: nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases.

Conclusions and relevance: this meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.

Adolescent, Child, Middle Aged, Humans, Female, Male, Aged, Cardiovascular Diseases/chemically induced, Attention Deficit Disorder with Hyperactivity/drug therapy, Heart Disease Risk Factors, Central Nervous System Stimulants/adverse effects, Heart Arrest, Observational Studies as Topic
e2243597
Zhang, Le
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Yao, Honghui
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Li, Lin
ee65a55e-7b94-43ac-94c2-43ccfaad2949
Du Rietz, Ebba
10cb0f63-64b1-49ef-b60c-8d483d93af17
Andell, Pontus
b2ad8849-eab1-485a-a9b9-63f4df4d156f
Garcia-Argibay, Miguel
b3dfd2f5-d33d-4e8e-8b44-540cbc5abb4c
D'Onofrio, Brian M
c0b7aed7-382b-46e8-8256-03346bb3a5d7
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Larsson, Henrik
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Chang, Zheng
86831bee-800b-469f-b67f-a5b7790cef80
Zhang, Le
1dc1ba6f-92bc-46cc-a73f-a16f21fb8e54
Yao, Honghui
02ccf08d-264c-4d9c-a8fb-3decb92539ec
Li, Lin
ee65a55e-7b94-43ac-94c2-43ccfaad2949
Du Rietz, Ebba
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Andell, Pontus
b2ad8849-eab1-485a-a9b9-63f4df4d156f
Garcia-Argibay, Miguel
b3dfd2f5-d33d-4e8e-8b44-540cbc5abb4c
D'Onofrio, Brian M
c0b7aed7-382b-46e8-8256-03346bb3a5d7
Cortese, Samuele
53d4bf2c-4e0e-4c77-9385-218350560fdb
Larsson, Henrik
4132f7c6-5d52-43a1-be38-d343e67107cf
Chang, Zheng
86831bee-800b-469f-b67f-a5b7790cef80

Zhang, Le, Yao, Honghui, Li, Lin, Du Rietz, Ebba, Andell, Pontus, Garcia-Argibay, Miguel, D'Onofrio, Brian M, Cortese, Samuele, Larsson, Henrik and Chang, Zheng (2022) Risk of cardiovascular diseases associated with medications used in Attention-Deficit/Hyperactivity Disorder: a aystematic review and meta-analysis. JAMA Network Open, 5 (11), e2243597. (doi:10.1001/jamanetworkopen.2022.43597).

Record type: Article

Abstract

Importance: use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.

Objective: to provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).

Data sources: PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.

Study selection: observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.

Data extraction and synthesis: independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline.

Main outcomes and measures: the outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.

Results: nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases.

Conclusions and relevance: this meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.

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e-pub ahead of print date: 23 November 2022
Keywords: Adolescent, Child, Middle Aged, Humans, Female, Male, Aged, Cardiovascular Diseases/chemically induced, Attention Deficit Disorder with Hyperactivity/drug therapy, Heart Disease Risk Factors, Central Nervous System Stimulants/adverse effects, Heart Arrest, Observational Studies as Topic

Identifiers

Local EPrints ID: 477158
URI: http://eprints.soton.ac.uk/id/eprint/477158
PURE UUID: 6fcb89f1-7219-49b9-88e6-3d02f0910faf
ORCID for Samuele Cortese: ORCID iD orcid.org/0000-0001-5877-8075

Catalogue record

Date deposited: 30 May 2023 16:44
Last modified: 17 Mar 2024 03:37

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Contributors

Author: Le Zhang
Author: Honghui Yao
Author: Lin Li
Author: Ebba Du Rietz
Author: Pontus Andell
Author: Miguel Garcia-Argibay
Author: Brian M D'Onofrio
Author: Samuele Cortese ORCID iD
Author: Henrik Larsson
Author: Zheng Chang

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