What is the appropriate treatment for a patient with numbness in the left arm, forearm, hand, and side of the lips, with normal brain Computed Tomography Angiography (CTA) and normal D-dimer, for stroke prophylaxis, considering the use of Plavix (clopidogrel)?

Antiplatelet Therapy for Suspected TIA/Minor Stroke

For a patient with transient neurological symptoms (numbness in left arm, forearm, hand, and lips) with normal brain CTA and normal D-dimer, aspirin 160-325 mg should be initiated within 48 hours, not clopidogrel alone. 1

Initial Management Approach

Start aspirin monotherapy (160-325 mg) immediately as the first-line antiplatelet agent for suspected TIA or minor ischemic stroke. 1 This recommendation is based on Class 1A evidence from the American College of Chest Physicians guidelines, which specifically recommend early aspirin therapy within 48 hours of symptom onset. 1

Why Not Clopidogrel Alone Initially?

• Aspirin is the recommended first-line agent for acute ischemic stroke or TIA, with the strongest evidence supporting its use within 48 hours of symptom onset. 1
• Clopidogrel monotherapy is reserved as an alternative for patients with aspirin allergy or contraindications. 1
• The FDA label for clopidogrel indicates it is approved for patients with "recent stroke" (within 6 months with residual neurological signs), not for acute management. 2

Dual Antiplatelet Therapy Considerations

Dual antiplatelet therapy (clopidogrel plus aspirin) should NOT be routinely used beyond 21-30 days due to increased bleeding risk without sustained benefit. 1

When Dual Therapy May Be Appropriate:

• If initiated, dual antiplatelet therapy must be started within 24-72 hours of symptom onset and continued for only 21-90 days maximum. 3, 4
• Recent evidence shows dual therapy (clopidogrel 300 mg loading, then 75 mg daily plus aspirin 100 mg daily) reduces recurrent stroke risk when started within 72 hours (7.3% vs 9.2% with aspirin alone, HR 0.79). 4
• However, this comes with increased bleeding risk (0.9% vs 0.4% moderate-to-severe bleeding, HR 2.08). 4
• The combination of clopidogrel plus aspirin is specifically NOT recommended within 3 months after stroke or TIA according to multiple guidelines. 1

Long-Term Secondary Prevention

For long-term stroke prophylaxis (beyond the acute period), choose ONE of the following: 1

1. Aspirin 75-100 mg daily (first-line option)
2. Clopidogrel 75 mg daily (preferred over aspirin based on direct comparison trials) 1, 5
3. Aspirin/extended-release dipyridamole 25/200 mg twice daily (also preferred over aspirin alone) 1, 5
4. Cilostazol 100 mg twice daily (less preferred alternative) 1

Evidence for Clopidogrel in Secondary Prevention:

• In the CAPRIE trial, clopidogrel showed an 8.7% relative risk reduction compared to aspirin (9.8% vs 10.6% event rate, p=0.045). 2
• However, the benefit was heterogeneous across subgroups - most apparent in peripheral arterial disease patients, less apparent in stroke patients, and not numerically superior in recent MI patients. 1, 2
• Clopidogrel is suggested over aspirin alone for long-term secondary prevention (Grade 2B). 1

Critical Diagnostic Considerations

Before committing to any antiplatelet regimen, complete the diagnostic workup: 1

• Confirm the diagnosis with follow-up MRI if initial CT was normal, as MRI is more sensitive for detecting acute ischemia. 1
• Screen for atrial fibrillation with prolonged cardiac monitoring (mobile telemetry or implantable loop recorder), as this would change management to anticoagulation rather than antiplatelet therapy. 1
• Evaluate for carotid stenosis with carotid duplex ultrasound or CTA/MRA, as significant stenosis may require revascularization plus medical therapy. 1
• Check lipid panel, HbA1c, and other vascular risk factors to guide comprehensive secondary prevention. 1

Common Pitfalls to Avoid

• Do not use dual antiplatelet therapy (clopidogrel plus aspirin) as routine long-term therapy - the MATCH and CHARISMA trials showed no benefit over monotherapy with increased bleeding risk. 1
• Do not assume normal CTA rules out stroke - up to 30% of TIAs may show infarction on follow-up MRI. 1
• Do not start clopidogrel alone without considering aspirin first unless there is a specific contraindication to aspirin. 1, 5
• Do not continue dual antiplatelet therapy beyond 90 days - bleeding risk outweighs benefit after this period. 1, 4

Practical Algorithm

1. Immediate (within 48 hours): Start aspirin 160-325 mg daily 1
2. Days 2-21: Continue aspirin 100 mg daily 1
3. After 21 days: Transition to long-term monotherapy with clopidogrel 75 mg daily OR aspirin 75-100 mg daily OR aspirin/dipyridamole 25/200 mg twice daily 1, 5
4. If high-risk features present (large vessel atherosclerosis, recurrent symptoms): Consider dual therapy for up to 21-90 days only, then transition to monotherapy 4

The answer to the specific question: No, this patient should NOT be started on Plavix (clopidogrel) alone. Start with aspirin 160-325 mg within 48 hours, then transition to long-term monotherapy with either clopidogrel 75 mg daily or aspirin 75-100 mg daily after completing the acute phase. 1, 5