What is the most appropriate oral antithrombotic therapy for a 68-year-old male with hypertension (High Blood Pressure), hyperlipidemia (Elevated Lipids), type 2 diabetes mellitus, and a history of smoking, who had an ischemic stroke with 50% stenosis in the left anterior cerebral artery?

Antithrombotic Therapy for Secondary Stroke Prevention in a 68-Year-Old Male

For this patient with a non-cardioembolic ischemic stroke (50% stenosis in left anterior cerebral artery), clopidogrel 75 mg once daily is the most appropriate oral antithrombotic therapy for secondary stroke prevention. 1

Patient Assessment and Stroke Classification

This 68-year-old male presents with:

• Acute ischemic stroke (confirmed by CT showing no hemorrhage)
• 50% stenosis in left anterior cerebral artery (non-cardioembolic etiology)
• Multiple vascular risk factors: hypertension, hyperlipidemia, type 2 diabetes, smoking history
• Already received fibrinolysis (r-tPA) for acute treatment

Recommended Antithrombotic Therapy

Evidence-Based Selection

The American College of Chest Physicians (ACCP) guidelines provide clear recommendations for patients with non-cardioembolic ischemic stroke:

• Long-term antiplatelet therapy is recommended over no antiplatelet therapy (Grade 1A) 1
• Among the recommended antiplatelet regimens, clopidogrel or aspirin/extended-release dipyridamole is suggested over aspirin (Grade 2B) 1

For this patient with multiple vascular risk factors and moderate arterial stenosis, clopidogrel offers several advantages:

1. Superior efficacy compared to aspirin alone for secondary prevention
2. Once-daily dosing (75 mg) improving adherence
3. Well-established safety profile in long-term use

Alternative Antiplatelet Options

While clopidogrel is recommended, other evidence-based options include:

• Aspirin (75-100 mg once daily)
• Aspirin/extended-release dipyridamole (25 mg/200 mg twice daily)
• Cilostazol (100 mg twice daily) 1, 2

However, clopidogrel has shown a 9% relative risk reduction in stroke, MI, or vascular death compared with aspirin alone 3, making it preferable for this high-risk patient.

Important Considerations

Timing of Initiation

• Antiplatelet therapy should be initiated immediately after fibrinolysis is complete and follow-up imaging confirms no hemorrhagic transformation 2
• Early aspirin therapy (160-325 mg) is recommended within 24-48 hours of stroke onset 1
• This can be transitioned to clopidogrel for long-term therapy

Duration of Therapy

• Long-term (indefinite) antiplatelet therapy is recommended for secondary prevention 1
• Regular monitoring for bleeding complications is essential

Avoiding Common Pitfalls

1. Do not use combination therapy with aspirin plus clopidogrel long-term - This combination increases bleeding risk without providing additional benefit for long-term secondary prevention (Grade 1B) 1

2. Do not use oral anticoagulation - For non-cardioembolic strokes, antiplatelet therapy is superior to oral anticoagulation (Grade 1B) 1

3. Consider CYP2C19 metabolism - Clopidogrel effectiveness depends on conversion to an active metabolite by CYP2C19; poor metabolizers may have diminished response 4

Follow-up and Monitoring

• Regular blood pressure monitoring (target <140/90 mmHg)
• Lipid management (high-intensity statin therapy)
• Diabetes control
• Smoking cessation counseling
• Monitoring for any bleeding complications

By implementing clopidogrel 75 mg daily as the oral antithrombotic therapy, along with aggressive management of vascular risk factors, this patient will receive optimal secondary stroke prevention based on current evidence.