Dual Antiplatelet Therapy in Ischemic Stroke
For patients with minor ischemic stroke (NIHSS ≤3-5) or high-risk TIA, initiate DAPT with aspirin plus clopidogrel within 24 hours and continue for 21-30 days, then transition to single antiplatelet therapy indefinitely. This approach reduces recurrent ischemic stroke by 32% without significantly increasing major bleeding risk during the short treatment window. 1
Patient Selection and Timing
Eligible patients include:
- Minor ischemic stroke with NIHSS score ≤3-5 2
- High-risk TIA with ABCD2 score ≥4-6 3, 2
- Non-cardioembolic stroke mechanism 2
- Symptom onset within 24 hours (ideally within 12 hours) 3, 2
Critical exclusion: Brain imaging must exclude intracranial hemorrhage before initiating DAPT 3, 2
DAPT Regimen
Loading dose:
- Aspirin 160-325 mg plus clopidogrel 300-600 mg 3
Maintenance dose:
- Aspirin 81 mg daily plus clopidogrel 75 mg daily 3
Alternative regimen: Aspirin plus ticagrelor for 30 days may be considered, though this combination has a 94% probability of being superior for minor stroke specifically, it carries higher bleeding risk than aspirin-clopidogrel 4, 2
Duration: The Critical Window
Short-duration DAPT (≤90 days) is effective and relatively safe:
- DAPT for 21-30 days reduces 90-day recurrent ischemic stroke risk by 32% (RR 0.68,95% CI 0.55-0.83) 1
- No significant increase in major bleeding during short-duration treatment (RR 1.88,95% CI 0.93-3.83) 1
- Maximum benefit occurs within the first 21 days 2
Long-duration DAPT (>90 days) is harmful:
- No reduction in recurrent ischemic stroke (RR 0.89,95% CI 0.79-1.02) 1
- 142% increased risk of major bleeding (RR 2.42,95% CI 1.37-4.30) 1
- Continuous DAPT beyond 90 days increases hemorrhage risk without additional benefit 2
Transition to Long-Term Therapy
After completing 21-30 days of DAPT, transition to single antiplatelet therapy indefinitely: 3, 2
- Aspirin 81-325 mg daily, OR
- Clopidogrel 75 mg daily, OR
- Aspirin 50 mg plus extended-release dipyridamole 200 mg twice daily 3
Evidence Quality and Strength
The American Heart Association/American Stroke Association 2021 guidelines are based on three high-quality short-duration randomized controlled trials that specifically enrolled patients with minor stroke or high-risk TIA 1. These trials demonstrated consistent benefit with low heterogeneity (I²=37.1%) for the primary outcome 1. The Revised Cochrane Risk-of-Bias tool rated these studies as having low to moderate risk of bias 1.
Special Populations and Considerations
Symptomatic intracranial atherosclerotic disease:
- Consider 90 days of DAPT followed by aspirin monotherapy 5
- Evidence is weaker for this specific population 2
Patients requiring urgent carotid endarterectomy:
- Consider aspirin monotherapy rather than DAPT to reduce perioperative bleeding risk 3
Cardioembolic stroke:
- Oral anticoagulation is recommended instead of antiplatelet therapy 3
- DAPT is specifically for non-cardioembolic mechanisms 2
Gastrointestinal bleeding risk:
- Consider proton pump inhibitors for patients at higher GI bleeding risk during DAPT 3
Common Pitfalls to Avoid
Do not extend DAPT beyond 30-90 days: This increases bleeding risk (NNH 284 for aspirin-ticagrelor, NNH 330 for aspirin-clopidogrel) without additional stroke prevention benefit 1, 3, 4
Do not delay initiation beyond 24 hours: Effectiveness decreases significantly when DAPT is started later than 24 hours after symptom onset 3, 2
Do not use triple antiplatelet therapy: The TARDIS trial demonstrated no benefit and significantly increased bleeding risk 1, 3, 2
Do not continue DAPT indefinitely: Patients must transition to monotherapy after the 21-30 day period to avoid long-term bleeding complications 3
Do not use DAPT for moderate-to-severe strokes: Older patients and those with more severe strokes have higher risk of intracranial hemorrhage with DAPT 1
Number Needed to Treat/Harm
For short-duration DAPT in minor stroke: