Single Antiplatelet Agent After 21 Days of DAPT in Non-Cardioembolic Stroke
After completing 21 days of dual antiplatelet therapy for minor ischemic stroke or high-risk TIA without a cardioembolic source, aspirin 75-100 mg daily is recommended as the single antiplatelet agent for long-term secondary prevention, with clopidogrel 75 mg daily as an equally effective alternative. 1, 2, 3
Transition Protocol from DAPT to Monotherapy
On Day 22, discontinue one of the two antiplatelet agents and continue with either aspirin 75-100 mg daily OR clopidogrel 75 mg daily indefinitely. 1, 2
The choice between aspirin and clopidogrel should be based on individual patient factors, as both agents demonstrate equivalent efficacy for long-term secondary prevention. 1, 3
Primary Recommendation: Aspirin Monotherapy
Aspirin 75-100 mg daily is the first-line recommendation for lifelong secondary prevention after completing the 21-day DAPT course. 1, 3
This low-dose aspirin regimen provides equivalent efficacy to higher doses (up to 1500 mg) while minimizing gastrointestinal bleeding risk. 1
The American Heart Association specifically endorses this dosing range as the standard maintenance dose for patients with recent noncardioembolic ischemic stroke or TIA. 1
Alternative Option: Clopidogrel Monotherapy
Clopidogrel 75 mg daily is an equally effective alternative to aspirin for long-term maintenance therapy. 1, 3
Clopidogrel should be preferentially selected for patients who are intolerant to aspirin or have contraindications such as aspirin allergy or significant gastrointestinal bleeding history. 1
The European Society of Cardiology recognizes clopidogrel as an equivalent alternative for long-term maintenance in this patient population. 1
Critical Safety Considerations
Do NOT continue dual antiplatelet therapy beyond 21-30 days for routine secondary prevention, as bleeding risk significantly increases (RR 1.88-2.42) without additional benefit. 1, 2, 3
The benefit-to-risk ratio favors dual therapy only during the first 21 days, with most stroke prevention occurring in the first week. 1, 2
Prolonged DAPT beyond 90 days significantly increases major hemorrhage risk (HR 2.22-2.32) without providing additional stroke prevention benefit. 1
Additional Monotherapy Option
Aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily represents a third reasonable alternative for long-term maintenance therapy. 1, 3
This combination is endorsed by the American Academy of Neurology as an alternative regimen for patients who cannot tolerate standard monotherapy options. 1
Common Pitfalls to Avoid
Never discontinue antiplatelet therapy entirely after the acute phase unless contraindicated or switching to anticoagulation for newly identified cardioembolic etiology. 1
Avoid using doses below 75 mg daily, as limited data support efficacy at lower doses. 1
Avoid using doses above 325 mg daily, as this increases bleeding complications without proportional benefit. 1
Do not use the combination of aspirin plus clopidogrel long-term in stable patients, as this significantly increases bleeding risk without improving outcomes. 1