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Risk of Cardiovascular Diseases Associated With ADHD Medications
Quick Takes
- This meta-analysis found no statistically significant association between use of attention-deficit/hyperactivity disorder (ADHD) medications and development of any type of cardiovascular disease (CVD).
- The lack of association was consistent across age groups, for both stimulant and nonstimulant medications, in subgroup analysis of specific CVD outcomes, and even in patients with pre-existing CVD.
- Given the high and statistically significant heterogeneity in the results of the included studies, the ability of this meta-analysis to reassure us on the cardiovascular safety of these medications may be limited.
Study Questions:
Are medications used to treat attention-deficit/hyperactivity disorder (ADHD) associated with an increased risk of cardiovascular disease (CVD)?
Methods:
This meta-analysis included 19 observational studies, published between 2007 and 2021, investigating the association of ADHD medications (stimulants and nonstimulants) with cardiovascular events: 14 cohort, three nested case-control, and two self-controlled case series. The primary outcome was development of any type of cardiovascular disease, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.
Results:
A total of 3,931,532 subjects from six countries (United States, South Korea, Canada, Denmark, Spain, and Hong Kong) were included. Follow-up time ranged from 0.25-9.5 years (median, 1.5 years). The most common data source was insurance claims databases. There was no statistically significant association between ADHD medication use and development of any form of CVD among any age groups. Pooled adjusted relative risk (RR) was 1.18 (95% confidence interval [CI], 0.91-1.53) for children and adolescents, 1.04 (95% CI, 0.43-2.48) for young or middle-aged adults, and 1.59 (95% CI, 0.62-4.05) for older adults. Likewise, none of the subgroup analyses revealed statistically significant associations, including stimulants vs. nonstimulants or specific CVD outcomes. Even in patients with pre-existing CVD, there was no association between use of ADHD medications and cardiovascular events (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant (Cochran’s Q test = 292.7, p < 0.001, I2 statistic = 93.2%).
Conclusions:
This meta-analysis found no statistically significant association between use of ADHD medications and development of any type of CVD. The lack of association was consistent across age groups, for both stimulant and nonstimulant medications, in subgroup analysis of specific CVD outcomes, and even in patients with pre-existing CVD. The utility of a meta-analysis in answering this question may be limited, however, by the high and statistically significant heterogeneity in the results of the studies included.
Perspective:
With the use of ADHD medications increasing worldwide and persistent concerns regarding their dopaminergic and noradrenergic effects, this meta-analysis addresses a clinically significant question, aiming to synthesize the available evidence on association of medication use and a broad range of CVDs. However, with the significant heterogeneity of the included studies, the ability of meta-analysis to answer this question is unclear. It is not surprising that no significant associations were found, given the span of positive and negative effect estimates (shown graphically in Figures 2 and 3) in the underlying data. The question is: How confident can we feel about the cardiovascular safety of these medications based on this study? The large confidence intervals suggest that higher quality evidence is needed.
Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Prevention, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Hypertension
Keywords: Attention Deficit Disorder with Hyperactivity, Cardiovascular Diseases, Cerebrovascular Disorders, Heart Arrest, Heart Failure, Hypertension, Myocardial Ischemia, Primary Prevention, Risk, Tachycardia, Venous Thromboembolism
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