What is the recommended dual antiplatelet therapy (DAPT) regimen for acute ischemic stroke?

Dual Antiplatelet Therapy for Acute Ischemic Stroke

For acute ischemic stroke, dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel should be initiated as early as possible (ideally within 12-24 hours) in patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4) for 21 days, followed by single antiplatelet therapy. 1

Recommended DAPT Regimens Based on Stroke Severity

Minor Ischemic Stroke (NIHSS ≤3) or High-Risk TIA (ABCD2 ≥4)

• Aspirin + Clopidogrel regimen:
  • Loading dose: Aspirin 160-325 mg + Clopidogrel 300-600 mg 1
  • Maintenance: Aspirin 81 mg daily + Clopidogrel 75 mg daily 1
  • Duration: 21 days 1
  • Follow with long-term single antiplatelet therapy (aspirin 81 mg daily or clopidogrel 75 mg daily) 1

Mild-Moderate Ischemic Stroke (NIHSS ≤5) or High-Risk TIA (ABCD2 ≥4)

• Aspirin + Ticagrelor alternative regimen:
  • Loading dose: Aspirin 300-325 mg + Ticagrelor 180 mg 1
  • Maintenance: Aspirin 75-100 mg daily + Ticagrelor 90 mg twice daily 1
  • Duration: 30 days 1
  • Follow with long-term single antiplatelet therapy 1

Important Implementation Guidelines

• Timing: Initiate DAPT as early as possible, ideally within 12-24 hours of symptom onset 1
• Prerequisite: Intracranial hemorrhage must be excluded on neuroimaging before starting therapy 1
• Administration route: For patients with impaired swallowing, rectal aspirin 325 mg daily or aspirin 81 mg/clopidogrel 75 mg via enteral tube are reasonable alternatives 1

Special Clinical Scenarios

• Intracranial atherosclerotic stenosis: DAPT with aspirin and clopidogrel is appropriate medical therapy for patients with moderate to high-grade (50-99%) intracranial atherosclerotic stenosis 1
• Embolic stroke of undetermined source (ESUS): Antiplatelet therapy is recommended rather than oral anticoagulants 1
• Extracranial artery dissection: Either antiplatelet therapy or oral anticoagulants are recommended for at least 3 months 1

Evidence Supporting Short-Term DAPT

• Recent studies show that short-duration DAPT (≤1 month) started during the early acute ischemic phase provides greater reduction in recurrent strokes compared to monotherapy 2, 3
• Short-term DAPT is associated with less bleeding than longer-term DAPT regimens 3
• The INSPIRES trial demonstrated that clopidogrel plus aspirin initiated within 72 hours after stroke onset led to a lower risk of new stroke at 90 days than aspirin alone (7.3% vs 9.2%), though with slightly higher risk of moderate-to-severe bleeding (0.9% vs 0.4%) 4

Safety Considerations and Monitoring

• Bleeding risk: DAPT increases the risk of intracranial bleeding (RR 1.55) and major bleeding (RR 1.90) compared to monotherapy, particularly with extended use 3, 5
• CYP2C19 poor metabolizers: Consider alternative P2Y12 inhibitors in patients identified as CYP2C19 poor metabolizers, as clopidogrel effectiveness depends on conversion to an active metabolite by this enzyme 6
• Drug interactions: Avoid concomitant use of clopidogrel with CYP2C19 inhibitors such as omeprazole or esomeprazole 6

Long-Term Antiplatelet Therapy After DAPT

• After completing the short-term DAPT course, continue with single antiplatelet therapy using either:
  • Aspirin 81 mg daily, or
  • Clopidogrel 75 mg daily 1
• For long-term secondary prevention in non-cardioembolic stroke, clopidogrel or aspirin/extended-release dipyridamole may be preferred over aspirin alone 1

Common Pitfalls to Avoid

• Prolonged DAPT: Extending DAPT beyond the recommended duration increases bleeding risk without additional benefit 3, 5
• Delayed initiation: Failing to start DAPT early (within 24 hours when possible) reduces its effectiveness 1, 2
• Premature discontinuation: Stopping antiplatelet therapy prematurely increases the risk of cardiovascular events 6
• Inadequate loading dose: Omitting the loading dose will delay establishment of an antiplatelet effect by several days 6