What is the recommended dose of antiplatelet (antithrombotic) therapy for patients with atherosclerosis (hardening of the arteries) in the legs, specifically those with peripheral arterial disease (PAD)?

Recommended Antiplatelet Dosing for Atherosclerotic Peripheral Arterial Disease

For patients with symptomatic atherosclerotic peripheral arterial disease (PAD), aspirin 75-100 mg daily or clopidogrel 75 mg daily is recommended as the standard antiplatelet therapy to reduce the risk of myocardial infarction, stroke, and vascular death. 1

First-Line Antiplatelet Options

• Aspirin: The recommended dose is 75-325 mg daily (typically 75-100 mg daily) for patients with symptomatic PAD, including those with intermittent claudication, critical limb ischemia, prior lower extremity revascularization, or prior amputation for lower extremity ischemia 1
• Clopidogrel: The recommended dose is 75 mg once daily as an effective alternative to aspirin for the same indications 1, 2

Patient-Specific Considerations

• Clopidogrel may be preferred over aspirin based on data from the CAPRIE trial, which demonstrated a 24% reduction in vascular events compared to aspirin in PAD patients 3
• For patients who are CYP2C19 poor metabolizers, consider using aspirin instead of clopidogrel, as clopidogrel's effectiveness depends on conversion to an active metabolite by the CYP2C19 enzyme 2

Dual Antiplatelet Therapy Considerations

• The combination of aspirin and clopidogrel may be considered in specific high-risk patients with symptomatic PAD who are not at increased risk of bleeding 1
• However, routine dual antiplatelet therapy is not recommended for most PAD patients as it does not provide significant benefit over single antiplatelet therapy and increases bleeding risk 1, 4

Special Situations

• Post-revascularization: For patients undergoing peripheral artery percutaneous transluminal angioplasty with stenting, at least four weeks of dual antiplatelet therapy (aspirin plus clopidogrel) is recommended after infrainguinal stent implantation 4
• Below-knee bypass with prosthetic grafts: Consider clopidogrel 75 mg daily plus aspirin 75-100 mg daily for 1 year 1
• Asymptomatic PAD: Aspirin 75-100 mg daily is suggested for patients with asymptomatic PAD (ABI ≤0.90) 1

Important Cautions

• Warfarin should not be added to antiplatelet therapy for PAD patients unless there is another specific indication, as this combination increases bleeding risk without providing additional cardiovascular benefit 1, 5
• For patients requiring temporary interruption of antiplatelet therapy for surgery, discontinue 5 days prior to elective procedures with major bleeding risk 2
• Monitor for bleeding complications, which are the most commonly reported adverse reactions with antiplatelet therapy 2

Adjunctive Therapies for Symptom Relief

• For patients with refractory claudication despite exercise therapy and smoking cessation, cilostazol 100 mg twice daily may be added to the antiplatelet regimen 1
• For critical limb ischemia with rest pain who cannot undergo revascularization, prostanoids may be considered in addition to antiplatelet therapy 1