What are the criteria for determining 21 days versus 90 days of dual antiplatelet therapy (aspirin and clopidogrel) in a patient with a history of transient ischemic attack (TIA) or ischemic stroke?

Criteria for 21 Days vs 90 Days of Dual Antiplatelet Therapy

Use 21 days of dual antiplatelet therapy (aspirin + clopidogrel) for minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), as this duration provides maximum benefit while minimizing bleeding risk; 90-day therapy is only indicated for the specific scenario of symptomatic intracranial atherosclerosis (70-99% stenosis). 1, 2

Standard Duration: 21 Days for Minor Stroke/High-Risk TIA

The 21-day regimen is the evidence-based standard for most patients:

• Initiate DAPT in patients with minor ischemic stroke (NIHSS 0-3) or high-risk TIA (ABCD2 score ≥4) of noncardioembolic origin within 24 hours of symptom onset 2
• The benefit of DAPT is confined to the first 21 days, with most stroke prevention occurring in the first week 2, 3
• Pooled analysis of 10,051 patients from the CHANCE and POINT trials demonstrated that DAPT reduced major ischemic events primarily within the first 21 days (HR 0.66), but showed no additional benefit from day 22 to day 90 3
• Continuing DAPT beyond 21-30 days significantly increases major hemorrhage risk without additional benefit 1, 2

Dosing Protocol for 21-Day Regimen

Loading and maintenance doses:

• Day 1: Aspirin 160-325 mg + clopidogrel 300-600 mg (loading dose) 1, 2
• Days 2-21: Aspirin 75-100 mg daily + clopidogrel 75 mg daily 1, 2
• After day 21: Transition to single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) indefinitely 1, 2

Extended Duration: 90 Days for Intracranial Atherosclerosis

The 90-day regimen is reserved for a specific high-risk subgroup:

• Use 90 days of DAPT (aspirin 325 mg + clopidogrel 75 mg) specifically for patients with recently symptomatic intracranial stenosis (70-99%) as part of aggressive medical management 4
• This recommendation is based on the medical management arm of the SAMMPRIS trial, which demonstrated superiority over intracranial stenting 4
• This extended duration must be combined with aggressive management of all vascular risk factors including blood pressure, lipids, and diabetes 4

Key Exclusion Criteria for DAPT

Do not use DAPT in these scenarios:

• Moderate to severe stroke (NIHSS >3) - use single antiplatelet therapy instead 1
• Low-risk TIA (ABCD2 <4) - use single antiplatelet therapy 1
• Symptom onset >24 hours - use single antiplatelet therapy 1, 2
• Cardioembolic stroke (atrial fibrillation or other cardioembolic source) - anticoagulation is indicated instead 2, 5
• Intracranial hemorrhage on imaging 2
• High bleeding risk (history of gastrointestinal bleeding, coagulopathy, concurrent anticoagulation) 1

Critical Safety Considerations

Bleeding risk increases significantly with prolonged therapy:

• Major hemorrhage risk increases with DAPT (RR 1.88-1.90) compared to aspirin alone 2
• The risk of major bleeding with DAPT beyond 90 days has a hazard ratio of 2.22-2.32 1
• Consider gastroprotection with proton pump inhibitors in patients with gastrointestinal bleeding risk factors during the 21-day DAPT period 1, 2

Common Pitfalls to Avoid

Critical errors in DAPT management:

• Never continue DAPT beyond 30 days in standard minor stroke/TIA patients - bleeding risk outweighs benefit 1, 2
• Do not delay initiation beyond 24 hours, as efficacy is time-dependent (ideally start within 12 hours) 2
• Do not use enteric-coated aspirin for loading dose due to slower onset of action 2
• DAPT is not a substitute for thrombolysis or thrombectomy in eligible patients 2
• Do not confuse the 90-day intracranial atherosclerosis indication with the standard 21-day minor stroke indication 4