Should a patient with a history of acute ischemic stroke be treated with single or dual antiplatelet therapy?

Antiplatelet Therapy for Acute Ischemic Stroke: Single vs. Dual Therapy

For most patients with acute ischemic stroke, start with single antiplatelet therapy (aspirin 160-325 mg loading dose, then 75-100 mg daily), but for patients with minor stroke (NIHSS ≤3) or high-risk TIA (ABCD2 score ≥4) of non-cardioembolic origin, use dual antiplatelet therapy (aspirin + clopidogrel) for 21-30 days, then transition to monotherapy. 1

Algorithm for Antiplatelet Selection

Step 1: Exclude Contraindications

• Rule out intracranial hemorrhage on brain imaging before any antiplatelet therapy 1
• Confirm patient passed dysphagia screening or use alternative routes (rectal suppository 325 mg or enteral tube 80 mg) 1
• Delay antiplatelet therapy until 24 hours post-thrombolysis if alteplase was administered 1

Step 2: Determine Stroke Severity and Risk Category

For Minor Stroke (NIHSS 0-3) or High-Risk TIA:

• Initiate dual antiplatelet therapy within 12-24 hours of symptom onset 1
• Loading doses: Clopidogrel 300-600 mg + Aspirin 160 mg 1
• Maintenance: Clopidogrel 75 mg + Aspirin 75-81 mg daily for exactly 21-30 days 1
• After 21-30 days: Switch to single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) indefinitely 1

High-risk TIA criteria (any of the following): 1

• ABCD2 score ≥4
• Transient, fluctuating, or persistent unilateral weakness (face, arm, leg)
• Symptom onset within last 48 hours

For Moderate to Severe Stroke or Standard-Risk TIA:

• Single antiplatelet therapy only 1
• Loading dose: Aspirin 160-325 mg immediately 1
• Maintenance: Aspirin 75-100 mg daily indefinitely 1
• Alternative: Clopidogrel 75 mg daily (no loading dose needed for long-term therapy) 1

Step 3: Special Considerations

For patients with large vessel intracranial atherosclerotic disease:

• Dual antiplatelet therapy may be continued for up to 90 days 1
• Requires careful monitoring for bleeding complications 1

For patients with cardioembolic stroke (atrial fibrillation):

• Anticoagulation (DOAC or warfarin) is required instead of antiplatelet therapy 1
• Do not use dual antiplatelet therapy in this population 1

For patients requiring urgent carotid endarterectomy:

• Consider aspirin monotherapy rather than dual therapy to reduce perioperative bleeding risk 1
• Coordinate timing with vascular surgeon 1

Evidence Supporting Dual Antiplatelet Therapy

The recommendation for short-term dual therapy is based on two landmark trials:

CHANCE Trial: 1

• Dual therapy (clopidogrel + aspirin) reduced 90-day stroke recurrence from 11.7% to 8.2% (HR 0.68, p<0.001)
• Treatment duration: 21 days
• Extracranial bleeding: 0.3% in both groups

POINT Trial: 1

• Dual therapy reduced ischemic stroke from 6.3% to 4.6% (HR 0.72, p=0.01)
• Major hemorrhage increased from 0.4% to 0.9% (HR 2.32, p=0.02)
• Net benefit: For every 1000 patients treated for 90 days, 15 ischemic strokes prevented but 5 major hemorrhages caused 1

This risk-benefit calculation is why guidelines limit dual therapy to 21-30 days only, not the full 90 days studied in POINT 1

Critical Safety Warnings

Do NOT continue dual antiplatelet therapy beyond 30 days for routine secondary prevention, as bleeding risk significantly increases (HR 2.22-2.32) without additional benefit 1

Do NOT use dual antiplatelet therapy for: 1

• Cardioembolic stroke (use anticoagulation instead)
• Patients with active bleeding or high bleeding risk
• Routine long-term secondary prevention beyond 30 days

Monitor for bleeding complications: 1

• Consider GI protection in patients at higher risk of GI bleeding
• Most benefit occurs in first week; bleeding risk persists throughout treatment

Long-Term Maintenance Therapy (After Acute Phase)

After completing dual therapy or for patients who received monotherapy from the start: 1

• Aspirin 75-100 mg daily (first-line option)
• Clopidogrel 75 mg daily (equally effective alternative)
• Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily (alternative option)

All three regimens are superior to no antiplatelet therapy (Grade 1A evidence) and should be continued indefinitely 1

Common Pitfalls to Avoid

• Do not delay aspirin beyond 48 hours in acute stroke—benefit is time-dependent with maximum efficacy when started early 1
• Do not use aspirin as substitute for thrombolysis in eligible patients—this delays definitive treatment 1
• Do not use glycoprotein IIb/IIIa inhibitors—these are potentially harmful in acute ischemic stroke 1
• Do not combine clopidogrel + aspirin long-term in stable patients—increases bleeding without benefit 1
• Do not use enteric-coated aspirin for loading dose—slower onset of action 2