What is the recommended dosage of aspirin (acetylsalicylic acid) and clopidogrel for primary and secondary stroke prevention?

Aspirin and Clopidogrel Dosing for Stroke Prevention

Secondary Prevention (After Stroke or TIA)

For patients with recent noncardioembolic ischemic stroke or TIA, aspirin 75-100 mg daily is the recommended long-term maintenance dose, with clopidogrel 75 mg daily as an equally effective alternative. 1

Acute Phase Dosing (First 24-48 Hours)

• Aspirin loading dose: Administer 160-325 mg as a single loading dose immediately after intracranial hemorrhage is ruled out on neuroimaging 2, 3
• For patients who received IV thrombolysis, delay aspirin until 24 hours post-treatment 2, 3
• After the loading dose, continue with 75-100 mg daily for long-term maintenance 1

Dual Antiplatelet Therapy (DAPT) for High-Risk Patients

For minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4) presenting within 24 hours:

• Loading doses: Aspirin 160-325 mg PLUS clopidogrel 300-600 mg 2, 4
• Maintenance: Aspirin 75-100 mg daily PLUS clopidogrel 75 mg daily for exactly 21 days 1, 2
• After 21 days: Switch to single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) 1, 2

The 21-day duration is critical—extending DAPT beyond 90 days significantly increases major hemorrhage risk (HR 2.22-2.32) without additional benefit 2. Short-term DAPT reduces stroke recurrence by 31% (RR 0.69) without increasing hemorrhagic stroke or major bleeding 5, 6.

Long-Term Maintenance (Beyond 21-30 Days)

Single antiplatelet therapy only:

• Aspirin 75-100 mg daily (first-line option) 1
• Clopidogrel 75 mg daily (equally effective alternative, particularly if aspirin intolerant) 1
• Aspirin 50 mg + extended-release dipyridamole 200 mg twice daily (reasonable alternative) 1

Long-term DAPT (beyond 90 days) does NOT reduce stroke recurrence (RR 0.92, p=0.15) but increases hemorrhagic stroke risk by 67% (RR 1.67) and major bleeding by 90% (RR 1.90) 5, 6. The SPS3 trial confirmed no benefit from adding clopidogrel to aspirin in patients already on aspirin (HR 0.91,95% CI 0.61-1.37) 1.

Special Populations

Intracranial stenosis (50-99%):

• Higher aspirin dose of 325 mg daily is specifically recommended 3

Patients already on aspirin who have recurrent stroke:

• Switch to clopidogrel 75 mg daily OR add extended-release dipyridamole 1
• Do NOT simply add clopidogrel to aspirin for long-term use 1

Primary Prevention

Aspirin is NOT routinely recommended for primary stroke prevention in asymptomatic individuals due to bleeding risks outweighing benefits in low-risk populations 1.

For patients with documented significant obstructive coronary artery disease but no prior MI or stroke, aspirin 75-100 mg daily is recommended 1.

Critical Dosing Considerations

Weight-Based Dosing

• Aspirin 75-100 mg for patients <70 kg
• Higher doses for patients >70 kg
• This applies to primary prevention; similar data for secondary stroke prevention are lacking 1

Common Pitfalls to Avoid

1. Do NOT use enteric-coated aspirin for loading doses—it has slower onset of action 2
2. Do NOT continue DAPT beyond 30 days unless specific high-risk features warrant it (number needed to harm for severe bleeding is 263 with ticagrelor-aspirin) 1
3. Do NOT use aspirin as substitute for thrombolysis or thrombectomy in eligible patients 2, 3
4. Do NOT combine aspirin with clopidogrel long-term in stable patients—bleeding risk exceeds benefit 1, 5
5. Avoid omeprazole and esomeprazole with clopidogrel—they reduce antiplatelet efficacy; use alternative PPIs if needed 1, 7

Alternative Routes for Dysphagia

• Aspirin 81 mg daily via enteral tube OR
• Aspirin 325 mg daily rectal suppository 3
• Clopidogrel 75 mg daily via enteral tube 4

Bleeding Risk Monitoring

The absolute bleeding risk with aspirin 160 mg daily equals that of 80 mg daily: 1-2 cases per 1000 patient-years, with identical fatal bleeding rates 8. However, doses of 75-162 mg daily balance efficacy with reduced bleeding risk for long-term use 1.