Can stimulants, such as Ritalin (methylphenidate) or Adderall (amphetamine and dextroamphetamine), increase the risk of myocardial infarction (heart attack)?

Can Stimulants Cause Heart Attack?

Stimulants used for ADHD do not increase the risk of myocardial infarction (heart attack) in the general population, based on large population-based studies showing no association between stimulant use and serious cardiovascular events including MI, sudden cardiac death, or stroke. 1, 2

Evidence from Population-Based Studies

The most robust evidence comes from a large retrospective cohort study of 150,359 adults (ages 25-64) matched with 443,198 nonusers, which found:

• No increased risk of MI, sudden cardiac death, or stroke with current stimulant use (adjusted rate ratio 0.83,95% CI 0.72-0.96) 2
• When comparing current users to remote users (to account for healthy-user bias), the adjusted rate ratio was 1.03 (95% CI 0.86-1.24), with the upper confidence limit corresponding to only 0.19-0.77 additional events per 1000 person-years 2
• The absolute incidence of MI during stimulant use was 1.34 per 1000 person-years 2

Multiple epidemiological studies using large administrative databases have demonstrated that stimulant medications have no effect, and possibly even a protective "healthy-user" effect on sudden cardiac death prevalence in children and adolescents 1

Cardiovascular Effects of Stimulants

Expected Physiological Changes

Stimulants cause modest, clinically insignificant cardiovascular changes in most patients:

• Average increases of 1-2 beats per minute in heart rate 1, 3
• Average increases of 1-4 mm Hg in systolic and diastolic blood pressure 1, 3
• These changes are generally not clinically significant 1

However, 5-15% of individuals may experience more substantial increases in heart rate and blood pressure, requiring monitoring 1

FDA Warnings and Context

The FDA issued a black box warning regarding stimulants and cardiovascular risk following an apparent cluster of sudden cardiac death events in patients receiving stimulants for ADHD 1. However, subsequent large epidemiological studies clearly demonstrated these medications have no effect on sudden cardiac death prevalence 1

The FDA drug label for amphetamines states that sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD, though the role of stimulants in these cases is unknown 4

High-Risk Populations Requiring Caution

Patients with Structural Heart Disease

Stimulants should generally not be used in patients with:

• Known structural cardiac abnormalities 4
• Cardiomyopathy 4
• Serious heart rhythm abnormalities 4
• Coronary artery disease 4
• Recent myocardial infarction 4
• Ventricular arrhythmia 4

These patients are at increased vulnerability to the sympathomimetic effects of stimulants 4

Patients with Long QT Syndrome (LQTS)

This is a critical exception to the general safety profile. Data from a large LQTS registry suggest that stimulant use was associated with increased risk of cardiac events, particularly in males with LQTS 1. However, a concurrent smaller study found no such effect, indicating consensus has not been reached 1

Patients with Uncontrolled Hypertension

Stimulants should be used with caution in patients with pre-existing hypertension, as they may worsen blood pressure control 3, 4. Blood pressure should be well-controlled (target <130/80 mm Hg) before initiating stimulant therapy 3

Pre-Treatment Cardiac Screening

Before initiating stimulant therapy, obtain:

• Detailed personal cardiac history, including specific cardiac symptoms (chest pain, syncope, palpitations) 1, 4
• Family history of sudden death, cardiovascular symptoms, Wolff-Parkinson-White syndrome, hypertrophic cardiomyopathy, and long QT syndrome 1
• Physical examination to assess for cardiac disease 4

If any cardiac risk factors are present, obtain additional cardiac evaluation (ECG, possibly echocardiogram, or cardiology referral) before starting stimulants 1, 4

Ongoing Monitoring

• Monitor heart rate and blood pressure at baseline and during treatment, as 5-15% of patients may have substantial increases 1
• Patients who develop exertional chest pain, unexplained syncope, or other cardiac symptoms during stimulant treatment should undergo prompt cardiac evaluation 4

Special Considerations

Adults vs. Children

Adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or coronary artery disease 4. Some studies suggest adults may have higher risk than children, with two out of three adult studies finding an association between stimulants and adverse cardiovascular outcomes, compared to only one out of seven pediatric studies 5

Combination Therapy Risks

One study showed 64% increased risk of cardiac-related events with concurrent stimulant and antidepressant use, and 90% increased risk with concurrent stimulant and antipsychotic use 6. These combinations warrant heightened monitoring 6

Case Reports

Individual case reports of acute myocardial infarction in adults taking stimulants exist 7, but these rare events must be interpreted in the context of large population studies showing no overall increased risk 2

Clinical Bottom Line

For patients without structural heart disease or significant cardiac risk factors, stimulants do not increase the risk of myocardial infarction. The absolute risk of serious cardiovascular events remains extremely low 1, 8, 2. However, appropriate pre-treatment screening and ongoing monitoring are essential to identify the minority of patients who may be at increased risk 1, 4.