Key PointsQuestion  Are attention-deficit/hyperactivity disorder (ADHD) medications associated with the risk of cardiovascular disease (CVD)?

Findings  This systematic review and meta-analysis based on 19 observational studies with more than 3.9 million participants suggested that there was no statistically significant association between ADHD medications and the risk of cardiovascular events among children and adolescents, young and middle-aged adults, or older adults.

Meaning  Despite no statistically significant association between ADHD medications and CVD, more evidence is needed for the potential risk of cardiac arrest and tachyarrhythmias, the cardiovascular risk in female patients and in those with preexisting CVD, and long-term risk.

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.