What is the recommended duration of dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor, such as clopidogrel, after a non-hemorrhagic stroke?

Duration of Dual Antiplatelet Therapy After Non-Hemorrhagic Stroke

Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel should be continued for only 21-30 days after a non-hemorrhagic stroke or high-risk TIA, followed by long-term single antiplatelet therapy. 1, 2

Evidence-Based Recommendations for DAPT Duration

Short-Term DAPT (21-30 days)

• For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4), DAPT with aspirin and clopidogrel should be limited to 21-30 days 1, 2
• The Canadian Stroke Best Practice Guidelines specifically recommend limiting DAPT to 21-30 days due to the increased risk of major hemorrhage with longer durations 1
• The American Heart Association/American Stroke Association guidelines support short-term DAPT, noting that the risk of hemorrhage begins to outweigh the benefit of stroke prevention as early as 21 or 30 days 1, 2

Specific DAPT Regimens

1. Aspirin + Clopidogrel regimen:

   • Loading dose: Aspirin 160-325mg + Clopidogrel 300-600mg
   • Maintenance: Aspirin 81mg daily + Clopidogrel 75mg daily
   • Duration: 21 days 1, 2

2. Aspirin + Ticagrelor regimen:

   • Loading dose: Aspirin 300-325mg + Ticagrelor 180mg
   • Maintenance: Aspirin 75-100mg daily + Ticagrelor 90mg twice daily
   • Duration: 30 days 2

Risks and Benefits Analysis

Benefits of Short-Term DAPT

• Reduces risk of recurrent stroke by 24-41% compared to monotherapy 2, 3
• For every 1000 patients treated with DAPT for 90 days, 15 ischemic strokes would be prevented 1
• Number needed to treat to prevent one primary outcome event is 92 2

Risks of Extended DAPT

• Significantly increased risk of major hemorrhage with longer durations 1
• For every 1000 patients treated with DAPT for 90 days, 5 major hemorrhages would result 1
• Number needed to harm for severe bleeding is 263 2
• Long-term DAPT (≥1 year) has been shown to have no benefit over single antiplatelet therapy for recurrent stroke prevention while significantly increasing bleeding risk 1, 3

Special Considerations

High-Risk Patients

• Older patients and those with more severe strokes appear to be at higher risk of intracranial hemorrhage with DAPT 1
• For patients with intracranial atherosclerotic stenosis (50-99%), DAPT is appropriate medical therapy but should still be limited to the recommended duration 1, 4

Transition to Long-Term Therapy

• After completing short-term DAPT, patients should transition to single antiplatelet therapy with either:
  • Aspirin 81-325mg daily
  • Clopidogrel 75mg daily
  • Aspirin 25mg + extended-release dipyridamole 200mg twice daily 2
• Single antiplatelet therapy should be continued indefinitely for secondary stroke prevention 1, 2

Clinical Pitfalls to Avoid

1. Extending DAPT unnecessarily: Continuing DAPT beyond the recommended 21-30 days increases bleeding risk without additional benefit in stroke reduction 1, 5
2. Delaying initiation: DAPT should be started as early as possible, ideally within 12-24 hours of symptom onset 2
3. Failing to exclude hemorrhage: Always rule out intracranial hemorrhage on neuroimaging before starting DAPT 2
4. Inadequate patient education: Patients must understand the short-term nature of DAPT and the importance of transitioning to long-term single antiplatelet therapy 2

In summary, while DAPT effectively reduces recurrent stroke risk in the short term, the evidence strongly supports limiting its duration to 21-30 days to optimize the balance between stroke prevention and bleeding risk.