What are the clinical criteria for starting dual anti-platelet therapy (DAPT) with aspirin and clopidogrel in patients with ischemic stroke?

Clinical Criteria for Starting Dual Antiplatelet Therapy in Ischemic Stroke

Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel should be initiated in patients with minor ischemic stroke (NIHSS 0-3) or high-risk TIA (ABCD2 score ≥4) of noncardioembolic origin, started within 24 hours of symptom onset, and continued for exactly 21 days before transitioning to single antiplatelet therapy. 1, 2

Patient Selection Criteria

Eligible Patients for DAPT

You must verify ALL of the following criteria before initiating DAPT:

• Stroke severity: NIHSS score 0-3 (minor stroke) OR high-risk TIA with ABCD2 score ≥4 1, 2
• Timing: Symptom onset within 24 hours (ideally within 12 hours) 1, 2
• Mechanism: Noncardioembolic origin (no atrial fibrillation or other cardioembolic source) 1, 2
• Imaging: Intracranial hemorrhage excluded on CT or MRI 1, 2
• Thrombolysis status: Not receiving or did not receive alteplase 1

Patients Who Should Receive Aspirin Monotherapy Instead

Do NOT use DAPT in the following situations:

• Moderate to severe stroke (NIHSS >3) 2, 3
• Low-risk TIA (ABCD2 score <4) 2, 3
• Presentation >24 hours after symptom onset 1, 2
• Cardioembolic mechanism (atrial fibrillation, mechanical valve, etc.) 1
• High bleeding risk (history of gastrointestinal hemorrhage, coagulopathy, concurrent anticoagulation) 2, 3

DAPT Dosing Protocol

Loading Dose (Day 1)

• Aspirin: 160-325 mg loading dose 1, 2
• Clopidogrel: 300-600 mg loading dose (minimum 300 mg based on CHANCE trial, up to 600 mg based on POINT trial) 1, 2

Maintenance Dose (Days 2-21)

• Aspirin: 75-100 mg daily 1, 2
• Clopidogrel: 75 mg daily 1, 2

After Day 21

• Transition to single antiplatelet therapy: Either aspirin 75-100 mg daily OR clopidogrel 75 mg daily 1, 2, 4

Critical Timing Considerations

DAPT must be started as early as possible to maximize benefit:

• Initiate within 24 hours of symptom onset (ideally within 12 hours) 1, 2
• Start prior to discharge from the emergency department 1
• The benefit of DAPT is confined to the first 21 days, with most stroke prevention occurring in the first week 2, 4
• Do NOT continue DAPT beyond 21-30 days as this significantly increases major hemorrhage risk (HR 2.22-2.32) without additional benefit 2, 3, 4

Evidence Supporting 21-Day Duration

The pooled analysis of CHANCE and POINT trials (10,051 patients) demonstrated that DAPT reduced major ischemic events within the first 21 days (HR 0.66,95% CI 0.56-0.77) but showed no benefit from day 22 to day 90. 4 For every 1000 patients treated with DAPT for 90 days, 15 ischemic strokes are prevented but 5 major hemorrhages occur. 1 The optimal risk-benefit ratio is achieved with 21 days of treatment. 2, 4, 5

Safety Monitoring

Bleeding Risk Assessment

• Major hemorrhage risk increases with DAPT (RR 1.88-1.90) compared to aspirin alone 5, 6
• Consider gastroprotection with proton pump inhibitors in patients with gastrointestinal bleeding risk factors 3
• Monitor for signs of intracranial or systemic bleeding during the 21-day treatment period 1, 5

Common Pitfalls to Avoid

• Do NOT use DAPT as a substitute for thrombolysis or thrombectomy in eligible patients 2
• Do NOT continue DAPT beyond 30 days as bleeding risk outweighs benefit 1, 2, 3
• Do NOT use enteric-coated aspirin for loading dose due to slower onset of action 2
• Do NOT delay initiation beyond 24 hours as efficacy is time-dependent 1, 2

Alternative DAPT Regimen

An alternative to clopidogrel is ticagrelor, particularly in patients with CYP2C19 loss-of-function alleles:

• Loading dose: Aspirin 160-325 mg + ticagrelor 180 mg 2
• Maintenance: Aspirin 75-100 mg daily + ticagrelor 90 mg twice daily for 21-30 days 2
• Network meta-analysis shows no significant difference between ticagrelor-aspirin and clopidogrel-aspirin for stroke prevention (HR 0.94,95% CI 0.78-1.13) 7