Should Plavix Be Taken for PVD?
Yes, clopidogrel (Plavix) 75 mg daily is strongly recommended for patients with symptomatic peripheral vascular disease (PVD/PAD) to reduce myocardial infarction, stroke, and vascular death. 1
Symptomatic PAD (Class I Recommendation)
For patients with symptomatic PAD—including those with claudication, prior lower extremity revascularization, or critical limb ischemia—antiplatelet therapy is a Class I, Level A recommendation. 1 You have two equally acceptable options:
- Clopidogrel 75 mg once daily (preferred by many based on CAPRIE trial data showing superior cardiovascular risk reduction compared to aspirin in PAD subgroup) 1
- Aspirin 75-325 mg daily (acceptable alternative) 1
The CAPRIE trial specifically demonstrated that clopidogrel was superior to aspirin for cardiovascular risk reduction in symptomatic PAD patients, with comparable bleeding rates. 1 The Antithrombotic Trialists' Collaboration meta-analysis showed a 22% odds reduction for cardiovascular events (MI, stroke, or vascular death) with antiplatelet therapy in symptomatic PAD. 1
Asymptomatic PAD (Class IIa Recommendation)
For asymptomatic patients with documented PAD (ABI ≤0.90), antiplatelet therapy with either clopidogrel or aspirin is reasonable to reduce cardiovascular events, though the evidence is less robust (Class IIa, Level C-EO). 1
Important caveat: For patients with borderline ABI (0.91-0.99), the benefit of antiplatelet therapy is uncertain (Class IIb). 1
Post-Revascularization Management
After peripheral artery revascularization (endovascular or surgical bypass), continue long-term single antiplatelet therapy with either clopidogrel 75 mg daily or aspirin 75-100 mg daily (Class I, Level A). 1, 2
Dual antiplatelet therapy (clopidogrel plus aspirin) is generally NOT recommended for most PAD patients, as it increases major bleeding risk without clear cardiovascular benefit (Class IIb for limb-related events only after revascularization). 1 The exception is below-knee prosthetic bypass grafts, where dual therapy for 1 year may be considered. 1
Key Clinical Pitfalls to Avoid
Do NOT combine clopidogrel with warfarin in PAD patients—this significantly increases bleeding risk without cardiovascular benefit (Class III: Harm, Level A). 1
Avoid omeprazole or esomeprazole with clopidogrel, as these proton pump inhibitors significantly reduce clopidogrel's antiplatelet activity through CYP2C19 inhibition. 3
Screen for CYP2C19 poor metabolizers if considering clopidogrel, as these patients (homozygous for nonfunctional CYP2C19 alleles) form less active metabolite and have reduced antiplatelet effect. Consider alternative P2Y12 inhibitors in identified poor metabolizers. 3
Comparison with Newer Agents
The EUCLID trial (2017) compared ticagrelor 90 mg twice daily versus clopidogrel 75 mg daily in 13,885 symptomatic PAD patients and found no superiority of ticagrelor over clopidogrel for cardiovascular events (10.8% vs 10.6%, HR 1.02, p=0.65), with similar bleeding rates. 4 This confirms clopidogrel remains the standard of care. 5
FDA-Approved Indication
Clopidogrel is FDA-approved specifically for patients with established peripheral arterial disease to reduce the rate of MI and stroke. 3 The approved dose is 75 mg once daily without a loading dose for chronic PAD management. 3
Additional Considerations
All PAD patients on clopidogrel should also receive:
- Statin therapy (Class I recommendation) regardless of baseline cholesterol 1, 2
- Antihypertensive therapy if hypertensive to reduce MI, stroke, and cardiovascular death 1, 2
- Smoking cessation counseling at every visit 1
If claudication persists despite exercise therapy and smoking cessation, add cilostazol 100 mg twice daily to baseline clopidogrel therapy. 1, 2