What are the recommended Dual Antiplatelet Therapy (DAPT) strategies, including dosages and regimens, for patients with high-risk Transient Ischemic Attack (TIA) or minor stroke, and how do these strategies differ for various stroke and TIA etiologies, including cardioembolic, atherosclerotic, and lacunar stroke, as well as major stroke?

Dual Antiplatelet Therapy (DAPT) for High-Risk TIA and Minor Stroke

For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), initiate DAPT with aspirin 81 mg daily plus clopidogrel 75 mg daily within 12-24 hours of symptom onset, continue for exactly 21 days, then transition to single antiplatelet therapy. 1

Loading Dose Protocol

Aspirin and Clopidogrel Regimen (Preferred):

• Loading dose: Aspirin 160-325 mg PLUS clopidogrel 300-600 mg on Day 1 1, 2
  • The 300 mg clopidogrel dose is based on the CHANCE trial 1
  • The 600 mg clopidogrel dose is based on the POINT trial 1
• Maintenance: Aspirin 81 mg daily PLUS clopidogrel 75 mg daily for Days 2-21 1
• After 21 days: Switch to single antiplatelet therapy with either aspirin 81 mg daily OR clopidogrel 75 mg daily 1

Alternative: Aspirin and Ticagrelor Regimen:

• Loading dose: Aspirin 300-325 mg PLUS ticagrelor 180 mg 1
• Maintenance: Aspirin 75-100 mg daily PLUS ticagrelor 90 mg twice daily for 30 days 1
• After 30 days: Switch to single antiplatelet therapy 1

Patient Selection Criteria

Eligible patients must meet ALL of the following: 1, 3

• Minor ischemic stroke (NIHSS ≤3) OR high-risk TIA (ABCD2 score ≥4)
• Non-cardioembolic etiology (no atrial fibrillation or cardioembolic source)
• Symptom onset within 24 hours (ideally within 12 hours)
• Intracranial hemorrhage excluded on CT or MRI
• Did NOT receive IV alteplase (or if alteplase given, delay DAPT until 24-hour post-thrombolysis scan excludes hemorrhage) 1

DAPT Strategies by Stroke Etiology

Intracranial Atherosclerotic Stenosis (50-99%)

• No strong evidence supports DAPT over single antiplatelet therapy for this specific etiology 1
• Aspirin 325 mg daily is recommended over anticoagulation 1
• DAPT may be appropriate as medical therapy when angioplasty/stenting is not recommended 1
• Post-hoc analysis of CHANCE trial showed no difference in DAPT benefit between patients with versus without intracranial atherosclerotic disease 1

Lacunar Stroke

• Use standard DAPT protocol if NIHSS ≤3: Aspirin plus clopidogrel for 21 days 1, 3
• No specific dosing modifications for lacunar etiology 1

Extracranial Carotid Stenosis

• Critical caveat: For patients with high-grade carotid stenosis who are candidates for urgent carotid endarterectomy or stenting, consider aspirin monotherapy instead of DAPT to reduce perioperative bleeding risk 1
• Coordinate with vascular surgeon/interventionalist regarding timing and antiplatelet selection 1

Extracranial Artery Dissection

• Either antiplatelet therapy OR anticoagulation for at least 3 months 1
• If choosing antiplatelet route, standard single antiplatelet therapy is recommended (no specific DAPT indication) 1

Embolic Stroke of Undetermined Source (ESUS)

• Do NOT use anticoagulation 1
• Standard antiplatelet therapy is recommended 1
• If meets criteria for minor stroke/high-risk TIA, use standard DAPT protocol 1

Cardioembolic Stroke

• DAPT is NOT indicated - these patients require anticoagulation, not antiplatelet therapy 2
• This is a critical exclusion criterion for DAPT protocols 1, 3

DAPT for Major Stroke

DAPT is NOT recommended for major stroke (NIHSS >3-5). 1, 3

For major stroke, use single antiplatelet therapy only:

• Aspirin 160-325 mg loading dose within 24-48 hours of onset 2
• If IV alteplase given, delay aspirin until 24 hours post-thrombolysis 1, 2
• Maintenance: Aspirin 75-100 mg daily OR clopidogrel 75 mg daily OR aspirin/dipyridamole 25/200 mg twice daily 1

Rationale: The evidence for DAPT is confined to minor stroke (NIHSS ≤3-5) and high-risk TIA populations 1, 3, 4. Patients with larger strokes have higher risk of hemorrhagic transformation, and DAPT increases bleeding risk without proven benefit in this population 1.

Critical Timing Considerations

• Initiate DAPT as early as possible, ideally within 12 hours of symptom onset 1, 3
• Maximum benefit occurs when started within 24 hours 1, 3
• Most stroke prevention occurs in the first week of treatment 3
• Do NOT delay initiation beyond 24 hours - efficacy is time-dependent 3

Duration and Transition Strategy

The 21-day duration is evidence-based and critical: 1, 3, 4

• Continuing DAPT beyond 21-30 days significantly increases major hemorrhage risk (RR 2.22-2.32) without additional benefit 2, 3
• The benefit-to-risk ratio favors DAPT only during the first 21 days 2
• Counsel patients explicitly that DAPT is temporary (21 days only) and they must transition to single antiplatelet therapy 1

After 21 days, choose ONE of the following for lifelong therapy: 1, 2

• Aspirin 75-100 mg daily (first-line)
• Clopidogrel 75 mg daily (equally effective alternative)
• Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily

Safety Monitoring and Bleeding Risk

DAPT increases bleeding risk: 3, 5

• Major hemorrhage: RR 1.88-2.42 compared to single antiplatelet therapy
• Intracranial hemorrhage: RR 1.55-1.76
• Absolute risk remains low (number needed to harm: 113-258)

Consider gastroprotection with proton pump inhibitors in patients with: 1, 3

• History of gastrointestinal bleeding
• Concurrent NSAID use
• Age >65 years with multiple risk factors

Monitor for bleeding during the 21-day treatment period 3

Common Pitfalls to Avoid

1. Never use DAPT as substitute for thrombolysis or thrombectomy in eligible patients - this delays definitive treatment and worsens outcomes 2, 3

2. Never continue DAPT beyond 30 days - bleeding risk outweighs benefit 1, 2, 3

3. Never use enteric-coated aspirin for loading dose - slower onset of action 2

4. Never initiate DAPT before excluding intracranial hemorrhage on neuroimaging 1, 3

5. Never use DAPT in patients with cardioembolic stroke - they require anticoagulation 1, 3

6. Never delay DAPT initiation beyond 24 hours - efficacy is time-dependent 1, 3

7. Never use DAPT for major stroke (NIHSS >3-5) - no evidence of benefit and increased bleeding risk 1, 3

Special Administration Routes

For patients with dysphagia: 1

• Rectal aspirin 325 mg daily OR
• Aspirin 81 mg daily via enteral tube PLUS clopidogrel 75 mg daily via enteral tube
• Transition to oral dosing once swallowing function returns

Evidence Quality

The DAPT recommendations are supported by high-quality evidence from multiple large randomized controlled trials (CHANCE, POINT, THALES) demonstrating 25-32% relative risk reduction in recurrent ischemic stroke 3, 4, 6. The European Stroke Organisation provides a strong recommendation based on high quality evidence for 21-day DAPT with aspirin and clopidogrel 4.