When do you initiate aspirin (acetylsalicylic acid) and Plavix (clopidogrel) in a patient with a history of ischemic stroke?

Timing of Aspirin and Clopidogrel Initiation in Acute Ischemic Stroke

For most patients with acute ischemic stroke, initiate aspirin 160-325 mg within 24-48 hours of symptom onset; dual antiplatelet therapy with aspirin plus clopidogrel should only be used in minor stroke (NIHSS ≤3) or high-risk TIA, initiated within 24 hours and continued for 21 days. 1

Critical Pre-Treatment Requirements

Before initiating any antiplatelet therapy:

• Brain imaging must exclude intracranial hemorrhage 2
• Do NOT start aspirin within 24 hours if the patient received IV thrombolysis due to significantly increased risk of intracranial bleeding 2, 1
• Wait at least 24 hours after rtPA administration before starting antiplatelet therapy 3

Standard Acute Ischemic Stroke Protocol

Aspirin Monotherapy (Most Patients)

• Loading dose: 160-325 mg aspirin within 24-48 hours of stroke onset 3, 1
• Maintenance: 50-100 mg daily for long-term secondary prevention 2
• This provides a small but statistically significant reduction in mortality and early recurrent stroke 3, 4, 5

Alternative Routes for Impaired Swallowing

• Rectal aspirin 325 mg 1
• Enteral tube administration: aspirin 81 mg 1

Dual Antiplatelet Therapy (DAPT): Restricted Indications Only

DAPT with aspirin plus clopidogrel is NOT recommended for routine acute ischemic stroke 1. The American College of Cardiology and American Heart Association classify this as Class III (not recommended) for general acute stroke treatment 1.

When DAPT IS Appropriate:

DAPT should only be used for:

• Minor stroke with NIHSS ≤3 1
• High-risk TIA (ABCD2 score ≥4) 1

DAPT Dosing Protocol (When Indicated):

1. Loading doses within 24 hours of symptom onset:

   • Clopidogrel 300-600 mg 6, 7
   • Aspirin 160-325 mg 6

2. Maintenance for 21-30 days:

   • Clopidogrel 75 mg daily 6
   • Aspirin 75-100 mg daily 6

3. After 21-30 days:

   • Transition to single antiplatelet therapy indefinitely 1, 6

Extended Time Window Evidence

Recent evidence supports DAPT initiation up to 72 hours after symptom onset in mild stroke:

• Patients with mild ischemic stroke or TIA benefit from DAPT when initiated within 72 hours 7
• Consistent stroke reduction observed whether started ≤24 hours, 24-48 hours, or 48-72 hours after onset 7
• However, guideline recommendations remain focused on the 24-hour window 1

Special Populations

Patent Foramen Ovale (PFO) with Atrial Septal Aneurysm:

• DAPT for 21-30 days, then indefinite aspirin monotherapy 50-100 mg daily 6

Hemorrhagic Transformation:

• Non-lobar hemorrhage with strong indications: Restart aspirin at 3-7 days if clinically stable 2
• Lobar hemorrhage: Delay aspirin minimum 4-6 weeks 2

Safety Considerations

Bleeding Risk with DAPT:

• Short-duration DAPT (≤1 month) has acceptable bleeding risk 8, 9
• Long-term DAPT (>1 month) significantly increases major bleeding and intracranial hemorrhage without additional benefit 8, 9
• Number needed to harm for intracranial bleeding with DAPT: 258 8

Contraindications:

• Active pathological bleeding (peptic ulcer, intracranial hemorrhage) 10
• Moderate-to-severe stroke if anticoagulation needed for non-cerebrovascular conditions 3

Critical Pitfalls to Avoid

• Never combine aspirin with thrombolysis within 24 hours - this is Class III (harmful) recommendation 3, 1
• Do not use DAPT for moderate-to-severe strokes - only for minor stroke/high-risk TIA 1
• Do not continue DAPT beyond 21-30 days - increases bleeding without benefit 8, 9
• Avoid omeprazole/esomeprazole with clopidogrel - significantly reduces antiplatelet activity 10
• Consider CYP2C19 poor metabolizers - clopidogrel may be ineffective; consider alternative P2Y12 inhibitor 10