What is the indication for Dual Antiplatelet Therapy (DAPT) with aspirin and another antiplatelet agent, such as clopidogrel, in patients with a Transient Ischemic Attack (TIA) and a high ABCD (Acute Brain Infarction, Blood pressure, Clinical features, Duration of TIA, Diabetes) score indicating a greater risk of subsequent stroke?

DAPT Indication in TIA with High ABCD Score and Stroke

For patients with high-risk TIA (ABCD2 score ≥4) or minor ischemic stroke (NIHSS ≤3-5), dual antiplatelet therapy with aspirin plus clopidogrel should be initiated within 12-24 hours of symptom onset and continued for 21 days, followed by transition to single antiplatelet therapy. 1

Patient Selection Criteria

High-risk TIA is defined as ABCD2 score ≥4, which qualifies patients for DAPT according to the 2021 AHA/ASA guidelines 1. The ABCD2 scoring system incorporates:

• Age ≥60 years (1 point)
• Blood pressure ≥140/90 mmHg (1 point)
• Clinical features: unilateral weakness (2 points) or speech disturbance without weakness (1 point)
• Duration: ≥60 minutes (2 points) or 10-59 minutes (1 point)
• Diabetes (1 point) 2

For minor ischemic stroke, patients with NIHSS ≤3 are eligible for DAPT, with some evidence supporting extension to NIHSS ≤5 when presenting within 24 hours 3. Patients with NIHSS >5 should not receive DAPT due to lack of evidence and increased bleeding risk 3.

DAPT Protocol and Dosing

Loading Dose

Administer aspirin 160-325 mg PLUS clopidogrel 300-600 mg as loading doses after intracranial hemorrhage has been excluded on neuroimaging 2, 3. The 300 mg clopidogrel loading dose is specifically validated for stroke/TIA patients, differing from the 600 mg dose used in acute coronary syndromes 4.

Maintenance Regimen

Continue aspirin 81 mg daily plus clopidogrel 75 mg daily for exactly 21 days (up to maximum 30 days), then transition to single antiplatelet therapy 2, 3. The benefit of DAPT is maximized within the first 21 days, with most stroke prevention occurring in the first week 1.

Timing Considerations

DAPT must be initiated within 12-24 hours of symptom onset to achieve optimal efficacy 2, 3. Early initiation within this window significantly reduces recurrent ischemic stroke (RR 0.66-0.73) and MACE (RR 0.78-0.81) 5. Treatment started later than 24 hours shows diminished benefit 1.

Evidence Supporting DAPT in High-Risk TIA

The recommendation is based on high-quality evidence demonstrating that short-term DAPT reduces recurrent ischemic stroke by 25-32% compared to single antiplatelet therapy in high-risk TIA and minor stroke patients 1, 6, 7. Specifically:

• Recurrent stroke reduction: RR 0.69-0.74 (26-31% relative risk reduction) 6, 7, 5
• MACE reduction: RR 0.76-0.77 (23-24% relative risk reduction) 7, 5
• Ischemic stroke reduction: RR 0.72-0.75 (25-28% relative risk reduction) 6, 7

The ABCD3-I score may provide even better risk stratification than ABCD2 alone, with high-risk patients showing adjusted HR 0.43 for stroke reduction with DAPT 8.

Safety Profile and Bleeding Risk

DAPT increases major bleeding risk (RR 1.88-2.42) and intracranial hemorrhage (RR 1.55-1.76), but the absolute risk remains low with number needed to harm of 113-258 1, 6. The bleeding risk is acceptable during the short 21-day treatment window but increases substantially with prolonged use 1.

Beyond 90 days, DAPT is associated with increased bleeding risk without additional stroke reduction benefit (RR 0.89 for recurrent stroke, not significant) 1. This is why guidelines explicitly recommend discontinuation after 21-30 days 1.

Critical Exclusion Criteria

Do NOT initiate DAPT until intracranial hemorrhage is ruled out on neuroimaging 2, 3. Additional contraindications include:

• Patients who received IV thrombolysis (delay aspirin 24 hours post-alteplase) 2
• High bleeding risk conditions 1
• Cardioembolic stroke requiring anticoagulation 2
• Severe stroke (NIHSS >5) 3

Transition to Long-Term Therapy

After 21 days of DAPT, switch to single antiplatelet therapy with aspirin 75-100 mg daily OR clopidogrel 75 mg daily 1, 2. Both agents are equally effective for long-term secondary prevention 2. An alternative is aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily 2.

Never continue DAPT beyond 90 days for routine secondary prevention, as this significantly increases hemorrhage risk (RR 2.22-2.42) without benefit 2, 4.

Common Pitfalls to Avoid

• Do not delay DAPT initiation beyond 24 hours, as efficacy is time-dependent with maximum benefit when started early 1, 5
• Do not use triple antiplatelet therapy (aspirin + clopidogrel + dipyridamole), which increases bleeding without additional benefit 1
• Do not use DAPT as substitute for thrombolysis or thrombectomy in eligible patients 2
• Do not continue DAPT long-term (>90 days) due to excess bleeding risk 1
• Do not use enteric-coated aspirin for loading dose due to slower onset of action 2

Algorithm Summary

1. Confirm high-risk TIA (ABCD2 ≥4) or minor stroke (NIHSS ≤3-5) presenting within 24 hours 1, 3
2. Exclude intracranial hemorrhage on neuroimaging 2, 3
3. Load with aspirin 160-325 mg + clopidogrel 300-600 mg within 12-24 hours 2, 3
4. Continue aspirin 81 mg + clopidogrel 75 mg daily for 21 days 1, 2, 3
5. Transition to single antiplatelet therapy (aspirin 75-100 mg OR clopidogrel 75 mg daily) 1, 2