What is the recommended antiplatelet therapy for a patient with a large Middle Cerebral Artery (MCA) infarct and an Alberta Stroke Programme Early Computed Tomography Score (ASPECTS) score of 5?

Treatment of Large MCA Infarct with ASPECTS 5

Primary Recommendation

For a patient with a large MCA infarct and ASPECTS score of 5, initiate single antiplatelet therapy with aspirin 160-325 mg as a loading dose within 24-48 hours after excluding intracranial hemorrhage, followed by maintenance therapy with aspirin 75-100 mg daily. 1, 2

Critical Context: Large Infarct Considerations

An ASPECTS score of 5 indicates extensive early ischemic changes involving more than one-third of the MCA territory, which represents a large infarct with significant hemorrhagic transformation risk. This fundamentally changes the risk-benefit calculation for antiplatelet therapy:

• Dual antiplatelet therapy (aspirin + clopidogrel) is NOT recommended for large infarcts due to substantially increased hemorrhagic transformation risk 3
• The CHANCE and POINT trials that demonstrated benefit of dual antiplatelet therapy specifically enrolled patients with minor stroke or high-risk TIA, not large infarcts 1, 2
• Experimental data demonstrates that dual antiplatelet therapy increases hemorrhagic transformation by 18.9 mm² when combined with thrombolysis in large infarcts 3

Treatment Algorithm

Step 1: Immediate Assessment (0-24 hours)

• Confirm absence of intracranial hemorrhage on neuroimaging before any antiplatelet administration 1, 2
• If thrombolysis was administered, delay aspirin until 24 hours post-treatment to minimize hemorrhagic risk 1, 2
• Assess for cardioembolic source (atrial fibrillation, valvular disease, LV thrombus) which would require anticoagulation instead 4

Step 2: Initiate Single Antiplatelet Therapy (24-48 hours)

• Loading dose: Aspirin 160-325 mg as a single dose 1, 2
• Avoid enteric-coated formulations for loading dose due to slower onset 1
• For patients unable to swallow: rectal aspirin 325 mg daily or aspirin 81 mg via enteral tube 1

Step 3: Maintenance Therapy (After 48 hours)

• Aspirin 75-100 mg daily for long-term secondary prevention 1, 2
• Alternative: Clopidogrel 75 mg daily if aspirin intolerant 1, 2
• Alternative: Aspirin 25 mg + extended-release dipyridamole 200 mg twice daily 1

Why NOT Dual Antiplatelet Therapy in This Case

The evidence for dual antiplatelet therapy specifically excludes large infarcts:

• CHANCE trial criteria: Minor stroke (NIHSS ≤3) or high-risk TIA, explicitly excluding large infarcts 1, 2
• POINT trial criteria: Minor stroke or high-risk TIA within 24 hours 1, 2
• Hemorrhagic risk: Large infarcts have inherently higher hemorrhagic transformation rates, which are further amplified by dual antiplatelet therapy 3
• Risk-benefit ratio: For every 1000 patients treated with dual therapy for 90 days, 15 ischemic strokes are prevented but 5 major hemorrhages occur—this ratio worsens dramatically in large infarcts 2

Monitoring Requirements

• First 24-72 hours: Close neurological monitoring for signs of deterioration or hemorrhagic transformation 2
• Bleeding surveillance: Monitor for gastrointestinal bleeding, intracranial hemorrhage, and other major bleeding complications 2
• Functional assessment: Serial neurological examinations to detect early deterioration 2

Common Pitfalls to Avoid

• Do NOT use dual antiplatelet therapy in large infarcts (ASPECTS ≤5) due to prohibitive hemorrhagic risk 3
• Do NOT delay aspirin beyond 48 hours in non-thrombolyzed patients, as benefit is time-dependent 1
• Do NOT use aspirin as substitute for thrombolysis or thrombectomy in eligible patients 1
• Do NOT continue high-dose aspirin (>100 mg) for maintenance after loading dose, as this increases bleeding without improving outcomes 1
• Do NOT use glycoprotein IIb/IIIa inhibitors, which are potentially harmful in acute ischemic stroke 1

Special Considerations for Cardioembolic Sources

If atrial fibrillation or other cardioembolic source is identified:

• Anticoagulation is preferred over antiplatelet therapy for long-term secondary prevention 4
• Timing of anticoagulation initiation: Typically delayed 1-2 weeks after large infarct to minimize hemorrhagic transformation risk 2
• Bridge therapy: Continue aspirin until anticoagulation is therapeutic 4

Evidence Quality

The recommendation for single antiplatelet therapy in acute ischemic stroke is supported by Grade 1A evidence from two large randomized controlled trials involving over 40,000 patients, demonstrating 13 fewer deaths or dependencies per 1000 patients treated 1. However, these trials did not specifically address large infarcts, making the risk-benefit calculation more conservative in this high-risk population.