What is the recommended duration of aspirin (acetylsalicylic acid) therapy for secondary prevention of ischemic stroke in patients with a history of ischemic infarct?

Duration of Aspirin Therapy for Secondary Prevention After Ischemic Stroke

Aspirin should be continued lifelong for secondary prevention in patients with a history of ischemic stroke. 1, 2

Initial Loading and Acute Phase (First 24-48 Hours)

• Administer aspirin 160-325 mg as a single loading dose within 24-48 hours after ruling out intracranial hemorrhage on neuroimaging. 2
• If the patient received IV thrombolysis (alteplase), delay aspirin initiation until 24 hours post-thrombolysis to minimize hemorrhagic risk. 2
• For patients unable to swallow, rectal aspirin 325 mg daily or enteral tube administration of 81 mg daily are reasonable alternatives. 2

Short-Term Dual Antiplatelet Therapy (Days 1-21/30)

For minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4):

• Initiate dual antiplatelet therapy (DAPT) with aspirin 75-100 mg plus clopidogrel 75 mg daily within 12-24 hours of symptom onset. 2, 3
• Continue DAPT for exactly 21 days (maximum 30 days), then transition to single antiplatelet therapy. 2, 3
• A loading dose of clopidogrel 300-600 mg plus aspirin 160-325 mg should be given at initiation. 2

Alternative regimen for specific populations:

• Aspirin 75-100 mg plus ticagrelor 90 mg twice daily for exactly 30 days may be used in patients with minor to moderate stroke, symptomatic intracranial/extracranial stenosis ≥30%, or high-risk TIA. 3
• This combination has a narrower indication and higher bleeding risk (0.5% severe bleeding vs 0.1% with aspirin alone) compared to aspirin-clopidogrel. 3

Long-Term Maintenance (After 21-30 Days Through Lifelong)

Single antiplatelet therapy should be continued indefinitely:

• Aspirin 75-100 mg daily is the first-line recommendation for lifelong secondary prevention. 1, 2
• Clopidogrel 75 mg daily is an equally effective alternative for patients intolerant to aspirin. 1, 2
• Aspirin 25 mg plus extended-release dipyridamole 200 mg twice daily is another reasonable alternative. 2

Do NOT continue dual antiplatelet therapy beyond 21-30 days in stable patients, as this significantly increases hemorrhage risk (hazard ratio 2.22-2.32) without additional benefit. 2, 3, 4

Critical Dosing Considerations

• The maintenance dose of 75-100 mg daily provides equivalent efficacy to higher doses (up to 1500 mg) while minimizing gastrointestinal bleeding risk. 1, 5, 6
• Doses below 75 mg have limited data supporting efficacy, while doses above 325 mg increase bleeding complications without proportional benefit. 1, 7, 8
• Even with optimal aspirin therapy, stroke recurrence rates remain approximately 2% per year, reflecting aspirin's modest 15-20% relative risk reduction. 9

Special Populations Requiring Different Approaches

Cardioembolic stroke (atrial fibrillation):

• Oral anticoagulation (NOAC or warfarin) is required instead of aspirin for patients with atrial fibrillation and CHA2DS2-VASc score ≥2 in males or ≥3 in females. 1
• Aspirin alone is inadequate for cardioembolic stroke prevention. 9

Mechanical prosthetic heart valves:

• Warfarin with INR target 3.0 (range 2.5-3.5) is required lifelong. 1
• Aspirin 75-100 mg may be added to warfarin if recurrent events occur despite adequate anticoagulation, provided bleeding risk is acceptable. 1

Severe intracranial stenosis (70-99%):

• These patients have stroke recurrence rates up to 18% per year despite standard antiplatelet therapy. 9
• Consider more aggressive blood pressure control (<130/80 mmHg), high-intensity statin therapy, and potentially dual antiplatelet therapy for 30 days. 9

Common Pitfalls to Avoid

• Never discontinue aspirin after the acute phase unless contraindicated or switching to anticoagulation for cardioembolic etiology. 1
• Do not use aspirin as a substitute for thrombolysis or mechanical thrombectomy in eligible acute stroke patients, as this delays definitive treatment. 2
• Avoid enteric-coated aspirin for loading doses due to slower onset of action; use non-enteric formulations. 2
• Do not continue aspirin plus clopidogrel beyond 21-30 days in stable patients without compelling indications (e.g., recent coronary stenting), as bleeding risk outweighs benefit. 2, 4

Monitoring and Optimization

• Ensure blood pressure control to target <140/90 mmHg (or <130/80 mmHg with severe stenosis). 9
• Add high-intensity statin therapy regardless of baseline lipid levels. 9
• Perform vascular imaging to identify large artery stenosis that may require intervention beyond medical therapy. 9
• If stroke recurs despite aspirin, investigate for cardioembolic source, severe stenosis, or consider alternative antiplatelet agents (clopidogrel or aspirin-dipyridamole). 9