When do we initiate antiplatelet therapy in a patient with a left Middle Cerebral Artery (MCA) infarct?

Timing of Antiplatelet Initiation in Left MCA Infarct

Initiate aspirin 160-300 mg within 24-48 hours of stroke onset in patients with left MCA infarct, but delay for 24 hours if IV alteplase was administered. 1

Standard Antiplatelet Initiation Protocol

For Patients NOT Receiving IV Alteplase

• Start aspirin 160-300 mg within 24-48 hours of symptom onset for all acute ischemic strokes, including left MCA territory infarcts 1
• This timing is based on Class I, Level A evidence from two large trials (IST and CAST) demonstrating reduced early recurrent stroke and improved long-term outcomes 1, 2, 3
• Administer orally if the patient can swallow safely; otherwise use rectal suppository or nasogastric tube 2, 3

For Patients Receiving IV Alteplase or Mechanical Thrombectomy

• Delay aspirin for 24 hours after thrombolytic therapy to minimize hemorrhagic risk 1
• After the 24-hour delay, initiate aspirin 160-300 mg unless hemorrhagic transformation has occurred 1
• One retrospective study suggested no increased hemorrhage risk with earlier initiation (<24 hours), but this may reflect selection bias and should not change standard practice 1

Special Considerations for Minor Stroke

Dual Antiplatelet Therapy (DAPT) Criteria

If the left MCA infarct qualifies as minor stroke (NIHSS ≤3), consider dual antiplatelet therapy:

• Initiate aspirin 160-325 mg PLUS clopidogrel 300-600 mg loading dose within 24-72 hours of symptom onset 1, 4, 5
• Continue with aspirin 81-100 mg daily plus clopidogrel 75 mg daily for exactly 21 days 1, 4, 5
• This regimen reduces new stroke risk at 90 days (7.3% vs 9.2% with aspirin alone) but increases moderate-to-severe bleeding (0.9% vs 0.4%) 5
• After 21 days, discontinue clopidogrel and continue single antiplatelet therapy indefinitely 1, 5

DAPT Contraindications

• Do NOT use DAPT if NIHSS >3 (moderate-to-severe stroke) 1
• Do NOT use DAPT if presenting >72 hours from symptom onset 4, 5
• Avoid ticagrelor as it showed no benefit over aspirin alone 1

Critical Timing Modifications for Hemorrhagic Transformation

Before Initiating Any Antiplatelet Therapy

• Obtain neuroimaging to exclude hemorrhagic transformation before starting antiplatelets, especially if considering DAPT 6

If Hemorrhagic Transformation is Present

The Heidelberg Classification determines timing:

• HI1 (small petechiae): May initiate aspirin within 24-48 hours after confirming no progression on repeat imaging 6
• HI2, PH1, PH2 (confluent petechiae or parenchymal hemorrhage): Delay ALL antiplatelets for 7-10 days minimum 6
• After 7-10 days with stable hemorrhage, restart with single antiplatelet agent (aspirin) only—avoid DAPT 6

Common Pitfalls to Avoid

• Do not substitute aspirin for acute reperfusion therapy (IV alteplase or thrombectomy) in eligible patients—aspirin is NOT a replacement for these treatments 1
• Do not use glycoprotein IIb/IIIa inhibitors (abciximab) as they cause harm in acute ischemic stroke 1
• Do not continue DAPT beyond 21-30 days as bleeding risk outweighs benefit (hazard ratio 2.22-2.32 for major hemorrhage) 7
• Do not initiate anticoagulation within 24 hours of IV alteplase even if atrial fibrillation is present 1
• Do not delay aspirin beyond 48 hours in patients without contraindications, as early treatment (within 48 hours) provides maximum benefit for preventing recurrent stroke 1, 2, 3

Dosing Summary

• Loading dose: Aspirin 160-325 mg (or 300-600 mg clopidogrel if DAPT indicated) 1, 2, 5
• Maintenance: Aspirin 81-100 mg daily (plus clopidogrel 75 mg daily for 21 days if DAPT) 1, 5
• Long-term: Single antiplatelet agent indefinitely after DAPT period ends 1, 5