What is the recommended discharge medication regimen for patients with peripheral artery disease (PAD) of the upper limb, including the role of anticoagulation?

Discharge Medication for Upper Limb Peripheral Artery Disease

Single antiplatelet therapy with either clopidogrel 75 mg daily or aspirin 75-160 mg daily is the cornerstone of discharge medication for symptomatic upper limb PAD, with clopidogrel preferred based on superior cardiovascular event reduction. 1, 2

Antiplatelet Therapy (Primary Recommendation)

For symptomatic upper limb PAD, prescribe single antiplatelet therapy at discharge:

• Clopidogrel 75 mg daily is the preferred first-line agent, demonstrating 24% relative risk reduction in cardiovascular events compared to aspirin in PAD patients 2, 3
• Aspirin 75-160 mg daily is an acceptable alternative if clopidogrel is contraindicated, unavailable, or not tolerated 1, 3

The 2024 ESC Guidelines provide Class I, Level A evidence for this recommendation, making it the strongest available evidence for antiplatelet therapy in PAD 1. While most PAD studies focus on lower extremity disease, the pathophysiology and thrombotic risk are identical in upper limb PAD, justifying extrapolation of these recommendations 1.

Role of Anticoagulation on Discharge

Anticoagulation monotherapy is NOT recommended for PAD unless a separate indication exists (such as atrial fibrillation, venous thromboembolism, or mechanical heart valve). 1

When Anticoagulation IS Indicated:

If the patient requires long-term anticoagulation for another indication:

• Continue single oral anticoagulant monotherapy (Class IIb recommendation) 1
• Do NOT add antiplatelet therapy routinely, as this significantly increases bleeding risk without proven cardiovascular benefit in most PAD patients 1

Dual Pathway Inhibition (Antiplatelet + Anticoagulant):

Consider rivaroxaban 2.5 mg twice daily PLUS aspirin 100 mg daily if ALL of the following criteria are met:

• High ischemic risk features present (previous amputation, chronic limb-threatening ischemia, prior revascularization, heart failure, diabetes, vascular disease in ≥2 beds, or eGFR <60 mL/min/1.73 m²) 1
• AND non-high bleeding risk (no history of intracranial hemorrhage, recent major bleeding, severe thrombocytopenia, or severe hepatic impairment) 1

This combination showed significant reduction in both major adverse cardiovascular events AND major adverse limb events in the COMPASS trial, though it increases gastrointestinal bleeding risk 4, 5. The 2024 ESC Guidelines assign this a Class IIa, Level A recommendation for high-risk PAD patients 1.

Post-Revascularization Considerations

If the patient underwent upper limb revascularization (endovascular or surgical):

• Continue long-term single antiplatelet therapy (aspirin 75-100 mg daily OR clopidogrel 75 mg daily) indefinitely 2, 3
• Dual antiplatelet therapy (aspirin + clopidogrel) may be considered for 1-6 months post-revascularization to reduce limb-related events, though evidence is limited (Class IIb) 1, 4
• Rivaroxaban 2.5 mg twice daily + aspirin 100 mg daily should be considered following revascularization in patients with non-high bleeding risk (Class IIa) 1

Essential Concomitant Discharge Medications

Beyond antithrombotic therapy, ALL upper limb PAD patients require:

• High-intensity statin therapy targeting LDL-C <70 mg/dL (Class I, Level A) 1, 3
• Antihypertensive therapy with target BP <140/90 mmHg (<130/80 mmHg if diabetes or CKD present), preferably ACE inhibitor or ARB (Class I, Level A) 1, 3, 6
• Smoking cessation pharmacotherapy (varenicline, bupropion, or nicotine replacement) if actively smoking (Class I, Level A) 1, 3
• Glycemic optimization (target HbA1c <7%) with GLP-1 agonists or SGLT-2 inhibitors if diabetic (Class IIa) 3, 6

Critical Pitfalls to Avoid

Do NOT prescribe:

• Warfarin or other vitamin K antagonists for PAD alone (Class III: Harm) 1, 7
• Long-term dual antiplatelet therapy (aspirin + clopidogrel) without specific high-risk indication, as bleeding risk outweighs benefit 1, 4
• Ticagrelor routinely for PAD, as it is not recommended by current guidelines 1, 3
• Antiplatelet therapy combined with full-dose anticoagulation unless absolutely necessary for another indication 1

Common error: Combining warfarin with antiplatelet therapy increases major bleeding risk by 2-3 fold without reducing cardiovascular events in PAD patients 1, 7. If anticoagulation is required for atrial fibrillation or other indication, use anticoagulant monotherapy rather than adding antiplatelet agents 1.