Amphetamines, Atomoxetine and the Risk of Serious Cardiovascular Events in Adults

<div><h3>Main Objective</h3><p>To compare the incidence rates of serious cardiovascular events in adult initiators of amphetamines or atomoxetine to rates in non-users.</p> <h3>Methods</h3><p>This was a retrospective cohort study of new amphetamines (n = 38,586) or atomoxetine (n = 20,995) users. Each medication user was matched to up to four non-users on age, gender, data source, and state (n = 238,183). The following events were primary outcomes of interest 1) sudden death or ventricular arrhythmia, 2) stroke, 3) myocardial infarction, 4) a composite endpoint of stroke or myocardial infarction. Cox proportional hazard regression was used to calculate propensity-adjusted hazard ratios for amphetamines versus matched non-users and atomoxetine versus matched non-users, with intracluster dependence within matched sets accounted for using a robust sandwich estimator.</p> <h3>Results</h3><p>The propensity-score adjusted hazard ratio for amphetamines use versus non-use was 1.18 (95% CI: 0.55–2.54) for sudden death/ventricular arrhythmia, 0.80 (95% CI: 0.44–1.47) for stroke, 0.75 (95% CI: 0.42–1.35) for myocardial infarction, and 0.78 (95% CI: 0.51–1.19) for stroke/myocardial infarction. The propensity-score adjusted hazard ratio for atomoxetine use versus non-use was 0.41 (95% CI: 0.10–1.75) for sudden death/ventricular arrhythmia, 1.30 (95% CI: 0.52–3.29) for stroke, 0.56 (95% CI: 0.16–2.00) for myocardial infarction, and 0.92 (95% CI: 0.44–1.92) for stroke/myocardial infarction.</p> <h3>Conclusions</h3><p>Initiation of amphetamines or atomoxetine was not associated with an elevated risk of serious cardiovascular events. However, some of the confidence intervals do not exclude modest elevated risks, e.g. for sudden death/ventricular arrhythmia.</p> </div

Incident ADHD medication users versus non-users and the incidence rates of serious cardiovascular events and all-cause death.

*<p>Standardized based on the major age distribution (18–47, 48–64, and 65+) of the overall incident user group.</p>†<p>Standardized based on the major age distribution (18–47, 48–64, and 65+) of the overall non-user group who were matched to incident users.</p>‡<p>Adjusted for continuous age and data source.</p>§<p>In the propensity score were all variables included that were listed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0052991#pone.0052991.s001" target="_blank">Appendix S1</a>.</p>**<p>Count omitted per Centers for Medicare & Medicaid Services Privacy Guideline policy.</p

Baseline characteristics of incident ADHD medication users and matched non-ADHD medication users, stratified by type of ADHD medication class.

*<p>Only available for the Medicaid population.</p>†<p>Cardiovascular disease/risk factor  =  sudden death/ventricular arrhythmia, myocardial infarction; stroke, cardiomyopathy, diabetes mellitus, heart failure, hypercholesterolemia, hypertension, ischemic heart disease.</p>‡<p>Treatment for cardiovascular disease/risk factor  =  use of angiotensin-converting enzyme inhibitor, use of aldosterone inhibitor, use of antiadrenergic agent, use of antiarrhythmic agent, use of antidiabetic agent, use of antihyperlipidemic agent, use of beta-blocker, use of calcium channel blocker, use of loop diuretics, use of nitrate, use of thiazide diuretic, and use of vasodilator.</p