Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults.

TitleAmphetamines, atomoxetine and the risk of serious cardiovascular events in adults.
Publication TypeJournal Article
Year of Publication2013
AuthorsSchelleman H, Bilker WB, Kimmel SE, Daniel GW, Newcomb C, Guevara JP, Cziraky MJ, Strom BL, Hennessy S
JournalPLoS One
Date Published2013
KeywordsAdrenergic Uptake Inhibitors, Amphetamines, Arrhythmias, Cardiac, Atomoxetine Hydrochloride, Cardiovascular Abnormalities, Death, Sudden, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Male, Myocardial Infarction, Proportional Hazards Models, Propylamines, Stroke

MAIN OBJECTIVE: To compare the incidence rates of serious cardiovascular events in adult initiators of amphetamines or atomoxetine to rates in non-users.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Alternate JournalPLoS ONE
PubMed ID23382829
PubMed Central IDPMC3559703
Grant ListUL1RR024134 / RR / NCRR NIH HHS / United States