Table 1 Population-Based Observational Studies of Prescription Stimulants and Adverse Cardiovascular Events
From: Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review
Year | Author | Study-Type/Drugs | Data Source | Population | Independent Variable | Outcome Variables | Statistical Approach | Result/Conclusion |
|---|---|---|---|---|---|---|---|---|
2007 | Winterstein et al. | Retrospective cohort/methylphenidate, amphetamines, and pemoline | Florida Medicaid | 3 to 20 years old with new diagnosis of ADHD (124,932 person-years) | Current use, former use, nonuse | 1) Cardiac Death | Cox regression | No increased risk of cardiac death or hospitalizations. Observed 20% increase in hazard for CV ER visits with current use over nonuse. |
2) First Cardiovascular (CV) Hospitalization | ||||||||
3) First CV ER visit | ||||||||
2009 | Winterstein et al. | Retrospective cohort/methylphenidate, amphetamine salts | Florida Medicaid | 3 to 20 years old with diagnosis of ADHD (52,783 person-years) and newly started on methylphenidate or amphetamine salts | Current use, former use | First CV ER visit | Cox regression | No difference in risk of first CV ER visit between methylphenidate and amphetamine salts |
2009 | Holick et al. | Retrospective matched cohort/atemoextine, “ADHD medication” (methylphenidate, amphetamine salts) | Health insurance database (Ingenix Research DataMart) | 18 years or older, atomoxetine initiators (n = 21,606) matched to “ADHD medication” initiators (n = 21,606) | Current use, recent use, past use, nonuse | 1) Cerebrovascular accident (CVA) | Propensity scoring, Cox regression | No increased risk of CVA or TIA with atomoxetine compared to stimulants. Increased risk of TIA with ADHD medication compared to general population (hazard ratio 3.44, 95% confidence interval 1.13-10.60). |
2) Transient ischemic attack (TIA) | ||||||||
2009 | McCarthy et al. | Descriptive cohort/methylphenidate, dextroamphetamine, atomoxetine | UK General Practice Research Database | 2 to 21 years old (18,637 person-years) | Ever used | Sudden death | Incident rate ratio, standardized mortality ratio | No increased risk of sudden death with stimulant and atomoxetine use. |
2009 | Gould et al. | Matched case–control/amphetamine, dextroampheamine, methamphamine, methylphenidate | State vital statistics offices | 7 to 19 years old, sudden death associated with stimulant use (n = 926) versus matched controls (n = 564; motor vehicle accident fatalities) | Stimulant use immediately prior to death | Sudden death | Logistic regression analysis of matched pairs | Increased risk of sudden death associated with stimulant use (odds ratio 7.4, 95% confidence interval 1.4 to 74.9). |
2011 | Schelleman et al. | Retrospective matched cohort/amphetamines, atomoxetine, methylphenidate | Medicaid (5 states) and health insurance database (HealthCore) | 3 to 17 years old incident ADHD medication users matched to nonusers | Current use | 1) Sudden death/ventricular arrhythmia | Proportional hazards regression | No statistically significant difference in rates of outcomes between exposed and non-exposed. |
2) Stroke | ||||||||
3) Myocardial infarction (MI) | ||||||||
4) Composite stroke/MI | ||||||||
2011 | Cooper et al. | Retrospective matched cohort/amphetamines, methylphenidate, pemoline, atomoxetine | Medicaid (Tennessee and Washington), health insurance databases (Kaiser Permanente California and OptumInsight Epidemiology), state death certificates, National Death Index | 2 to 24 years old ADHD medication users matched to nonusers (2,579,104 person-years) | Current use, former use, nonuse | 1) Sudden cardiac death | Cox regression, propensity scoring | No increased risk of serious cardiovascular events for current users (adjusted hazard ratio 0.75, 95% confidence interval 0.31 to 1.85). |
2) Stroke | ||||||||
3) Myocardial infarction | ||||||||
2011 | Habel et al. (Journal of the American Medical Association) | Retrospective matched cohort/amphetamines, methyldphenidate, pemoline, atomoxetine | Tennessee Medicaid, health insurance databases (Kaiser Permanente California and OptumInsight Epidemiology), HMO Research Network, state death records, National Death Index | Adults 25 to 64 years old ADHD medication users matched to nonusers (806,182 person-years) | Current use, indeterminate use, former use, remote use, nonuse | 1) Myocardial infarction (MI) | Poisson regression adjusted by cardiovascular risk score and confounders; propensity scoring and external adjustment methods used in secondary analyses | No increased risk of serious cardiovascular events (MI/SCD/stroke) for current users compared to nonusers (adjusted rate ratio 0.83, 95% confidence interval 0.72-0.96) |
2) Sudden cardiac death (SCD) | ||||||||
3) Stroke | ||||||||
2012 | Schelleman et al. | Retrospective matched cohort/methylphenidate | Medicaid (5 states) and health insurance database (HealthCore) | 18 years and older methylphenidate users (n = 43,999) matched to nonusers (n = 175,955) | Current use, nonuse | 1) Sudden death/ventricular arrhythmia | Proportional hazards regression adjusted for age and data source; propensity scoring as secondary analysis | Increased risk of sudden death or ventricular arrhythmia for current users (adjusted hazard ratio 1.84, 95% confidence interval 1.33 to 2.55). No increased risk of stroke, myocardial infarction, or composite stroke/MI. |
2) Stroke | ||||||||
3) Myocardial infarction (MI) | ||||||||
4) Composite stroke/MI | ||||||||
2012 | Olfson et al. | Retrospective cohort/methylphenidate, amphetamines | Health insurance database (MarketScan Research Databases) | 6 to 21 years old with ADHD and non know cardiovascular risk factors, treated with stimulants (n = 89,031) or not treated with stimulants (n = 82,095) | Current use, former use, nonuse | 1) Severe cardiovascular events (AMI, subarachnoid hemorrhage, stroke, ischemic heart disease, sudden death, respiratory arrest | Logistic regression adjusted for age, days from index diagnosis, and propensity score | No analysis for severe cardiovascular events was performed due to only one incident event in the entire cohort. For less severe cardiovascular events, there was no increased risk associated with stimulant use compared to nonuse (adjusted odds ratio 0.69, 95% CI 0.42-1.12) |
2) Less severe cardiovascular events (angina pectoris, cardiac dysrhythmias, transient cerebral ischemia) |