What is the recommended management for patients with peripheral artery disease (PAD) at high risk of bleeding?

Antithrombotic Management for PAD Patients at High Risk of Bleeding

For patients with peripheral artery disease (PAD) at high risk of bleeding, single antiplatelet therapy with clopidogrel 75 mg daily is recommended as the preferred antithrombotic strategy. 1

Risk Assessment and Antithrombotic Selection Algorithm

When managing PAD patients with high bleeding risk, follow this structured approach:

1. Identify bleeding risk factors:

   • History of intracranial hemorrhage
   • Recent stroke or TIA
   • Active or clinically significant bleeding
   • Severe renal impairment (GFR <15 mL/min/1.73 m²) or dialysis
   • Advanced age
   • Concomitant use of medications increasing bleeding risk
   • History of gastrointestinal bleeding

2. Select appropriate antithrombotic therapy based on clinical presentation:

For Asymptomatic PAD with High Bleeding Risk

• No antithrombotic therapy is recommended
• Avoid routine antiplatelet therapy 1

For Symptomatic PAD with High Bleeding Risk

• First choice: Clopidogrel 75 mg daily monotherapy 1
• Alternative: Aspirin 75-100 mg daily if clopidogrel is contraindicated 1

For PAD After Revascularization with High Bleeding Risk

• First choice: Single antiplatelet therapy (SAPT) with clopidogrel 75 mg daily 1
• Alternative: Aspirin 75-100 mg daily 1
• Limit dual antiplatelet therapy (DAPT) duration to minimum necessary period (≤1 month) 1

Evidence-Based Rationale

The 2024 ACC/AHA/AACVPR guidelines strongly recommend single antiplatelet therapy for symptomatic PAD patients 1. For those at high bleeding risk, clopidogrel monotherapy offers advantages over other regimens:

1. Clopidogrel vs. Aspirin: Clopidogrel demonstrated superior efficacy compared to aspirin for prevention of major adverse cardiovascular events (MACE) with similar bleeding rates 1, 2.

2. Avoid Combination Therapy: The 2024 ESC guidelines explicitly state that long-term dual antiplatelet therapy in PAD patients is not recommended, particularly important for those at high bleeding risk 1.

3. Avoid Anticoagulants: Full-intensity oral anticoagulation without another indication (e.g., atrial fibrillation) is harmful in PAD patients and should not be used 1. The combination of antiplatelet therapy with warfarin increases major bleeding risk without additional benefit 1.

Special Considerations

• For patients requiring anticoagulation (e.g., atrial fibrillation): Use oral anticoagulant monotherapy without additional antiplatelet therapy 1.

• After endovascular procedures: If DAPT is absolutely necessary, limit to shortest possible duration (≤1 month) in high bleeding risk patients 1.

• Rivaroxaban plus aspirin combination: While effective in reducing MACE and major adverse limb events (MALE) in standard-risk patients 1, this combination should be avoided in high bleeding risk patients due to increased bleeding concerns.

Monitoring and Follow-up

• Regularly assess for bleeding complications
• Monitor for signs of limb ischemia despite antithrombotic therapy
• Reassess bleeding risk periodically as risk factors may change over time

By following this algorithm, clinicians can optimize the balance between preventing thrombotic events and minimizing bleeding complications in PAD patients at high risk of bleeding.