Duration of Dual Antiplatelet Therapy in Stroke
For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA, dual antiplatelet therapy (aspirin plus clopidogrel) should be given for 21 days, not longer, as extending beyond this period significantly increases major bleeding risk without additional benefit. 1
Specific Treatment Protocol
Loading and Maintenance Dosing
- Loading dose: Aspirin 160-325 mg + clopidogrel 300-600 mg on day 1 1, 2
- Maintenance dose: Aspirin 81-100 mg daily + clopidogrel 75 mg daily 1, 2
- Duration: 21 days maximum, then transition to single antiplatelet therapy 1
Initiation Time Window
The evidence supports DAPT initiation within 72 hours of symptom onset:
- Within 24 hours: Established benefit with hazard ratio 0.83 for stroke recurrence 3
- 24-48 hours: Hazard ratio 0.85 for stroke recurrence 3
- 48-72 hours: Hazard ratio 0.70 for stroke recurrence, showing consistent benefit across all time windows 3
The most recent high-quality evidence from the INSPIRES trial (2023-2024) demonstrates that DAPT initiated up to 72 hours after symptom onset reduces new stroke risk by 21-30% compared to aspirin alone 2, 3.
Patient Selection Criteria
Who Should Receive DAPT
- Minor ischemic stroke with NIHSS ≤3 1
- High-risk TIA with ABCD2 score ≥4 1
- Presentation within 72 hours of symptom onset 2, 3
- Presumed atherosclerotic etiology 2
Who Should Receive Aspirin Monotherapy Instead
- Moderate to severe stroke (NIHSS >3) 1
- Low-risk TIA (ABCD2 <4) 1
- Presentation >24 hours after symptom onset (though recent evidence extends this to 72 hours) 1
- High bleeding risk (history of gastrointestinal bleeding, anticoagulant use, coagulopathy) 1
Critical Safety Considerations
Bleeding Risk Timeline
The meta-analysis data clearly shows that prolonged DAPT beyond 90 days increases major hemorrhage risk with hazard ratio 2.22-2.32 4. Even at 90 days, the bleeding risk outweighs benefits compared to the 21-day regimen 1.
The INSPIRES trial found moderate-to-severe bleeding occurred in 0.9% with DAPT versus 0.4% with aspirin alone, representing a doubling of bleeding risk (HR 2.08) 2. This risk remains consistent across all initiation time windows 3.
Gastrointestinal Protection
- Consider proton pump inhibitors in patients with risk factors for gastrointestinal bleeding during the 21-day DAPT period 1
Post-DAPT Management
After completing 21 days of DAPT, transition to long-term single antiplatelet therapy (aspirin 81 mg daily OR clopidogrel 75 mg daily) indefinitely for secondary stroke prevention 1.
Common Pitfall to Avoid
The most critical error is extending DAPT beyond 21-30 days based on older cardiac literature or perceived high stroke risk. The stroke-specific evidence is unequivocal: duration beyond 21 days increases hemorrhagic complications without reducing ischemic events 1, 4. This differs fundamentally from coronary stenting protocols where longer DAPT durations are sometimes appropriate 5.
For symptomatic intracranial stenosis specifically, DAPT up to 90 days may be considered as part of aggressive medical management, but this represents a distinct clinical scenario 6.