When to Add Plavix (Clopidogrel) for Stroke
For patients with minor ischemic stroke (NIHSS ≤3) or high-risk TIA (ABCD2 ≥4), dual antiplatelet therapy with clopidogrel plus aspirin should be initiated as early as possible within 12-24 hours of symptom onset, after excluding intracranial hemorrhage on neuroimaging. 1
Acute Phase: Dual Antiplatelet Therapy (DAPT)
Eligibility Criteria
- Minor ischemic stroke with NIHSS ≤3 or high-risk TIA with ABCD2 score ≥4 1
- Symptom onset within 72 hours (ideally within 12-24 hours for optimal benefit) 1, 2
- Intracranial hemorrhage excluded on CT or MRI 1, 3
- Non-cardioembolic stroke (no indication for anticoagulation) 1
Loading Dose Protocol
- Clopidogrel: 300-600 mg loading dose on day 1 1, 3, 2
- Aspirin: 160-325 mg loading dose on day 1 1, 3
- This loading strategy rapidly inhibits platelet aggregation, as standard 75 mg daily dosing takes approximately 5 days to achieve maximal effect 1, 3
Maintenance Regimen
- Clopidogrel 75 mg daily plus aspirin 81-100 mg daily for 21 days 1
- After 21 days, transition to single antiplatelet therapy (either clopidogrel 75 mg daily OR aspirin 81 mg daily) 1
Extended Time Window Evidence
Recent high-quality evidence demonstrates that DAPT initiated up to 72 hours after symptom onset still provides benefit, though earlier initiation (within 24 hours) shows the strongest effect 2. The INSPIRES trial (2023) showed that clopidogrel-aspirin reduced new stroke risk at 90 days (7.3% vs 9.2%, HR 0.79) when initiated within 72 hours, with consistent benefit across all time windows 2.
Long-Term Secondary Prevention
When NOT to Use Dual Antiplatelet Therapy Long-Term
After the initial 21-30 day period, long-term DAPT (clopidogrel plus aspirin) is NOT recommended for secondary stroke prevention 1. The 2012 CHEST guidelines explicitly recommend against the combination of clopidogrel plus aspirin for long-term use (Grade 1B) 1.
Long-Term Single Agent Options
For patients with non-cardioembolic ischemic stroke or TIA requiring long-term antiplatelet therapy, choose ONE of the following 1:
- Clopidogrel 75 mg daily (preferred over aspirin) 1
- Aspirin 75-100 mg daily 1
- Aspirin/extended-release dipyridamole 25/200 mg twice daily 1
The 2012 CHEST guidelines suggest clopidogrel or aspirin/extended-release dipyridamole over aspirin monotherapy for long-term use (Grade 2B) 1.
Special Populations
Intracranial Atherosclerotic Stenosis (50-99%)
For patients with moderate-to-high-grade intracranial atherosclerotic stenosis, dual antiplatelet therapy is appropriate medical therapy rather than angioplasty/stenting 1.
Patients on Thrombolysis
Do NOT initiate any antiplatelet therapy within 24 hours of IV tPA administration 1. After 24 hours, aspirin 160-325 mg should be started 1.
Swallowing Impairment
For patients unable to swallow, clopidogrel 75 mg daily can be administered via enteral tube 1, 3.
Safety Considerations
Bleeding Risk
DAPT carries a low but significantly increased risk of moderate-to-severe bleeding compared to aspirin alone 2:
- Moderate-to-severe bleeding: 0.9% with DAPT vs 0.4% with aspirin alone (HR 2.08) 2
- Number needed to harm: 258 for intracranial bleeding, 113 for major bleeding 4
- This risk is acceptable given the substantial reduction in recurrent stroke during the acute phase 2, 4
Critical Exclusions
- Do NOT use if intracranial hemorrhage present on imaging 1, 3
- Do NOT use if patient requires anticoagulation (e.g., atrial fibrillation) 1
- Do NOT use for moderate-to-severe strokes (NIHSS >5 with aspirin-clopidogrel regimen) 1
Common Pitfalls to Avoid
- Delaying initiation beyond 24 hours: While benefit extends to 72 hours, earlier initiation (12-24 hours) provides maximum benefit 1, 2
- Continuing DAPT beyond 21-30 days: Long-term DAPT increases bleeding risk without additional stroke prevention benefit 1, 4
- Using DAPT in cardioembolic stroke: These patients require anticoagulation, not dual antiplatelet therapy 1
- Forgetting the loading dose: Standard maintenance dosing without loading delays therapeutic effect by several days 1, 3