What is the role of Direct Oral Anticoagulants (DOACs) in managing Peripheral Artery Disease (PAD)?

Role of Direct Oral Anticoagulants (DOACs) in Peripheral Artery Disease Management

For patients with PAD, DOACs at standard doses should NOT be used unless there is another indication such as atrial fibrillation or venous thromboembolism, as full-intensity oral anticoagulation is harmful in PAD without other indications. 1

Primary Antithrombotic Recommendations for PAD

PAD without Another Indication for Anticoagulation

• First-line therapy: Single antiplatelet therapy (SAPT) with either aspirin (75-100 mg daily) or clopidogrel (75 mg daily) for symptomatic PAD
• For high ischemic risk patients with non-high bleeding risk: Low-dose rivaroxaban (2.5 mg twice daily) plus low-dose aspirin (100 mg daily) can reduce major adverse cardiovascular events (MACE) and major adverse limb events (MALE), but increases bleeding risk 1
• Avoid: Full-intensity oral anticoagulation (standard DOAC doses or warfarin) should NOT be used for PAD alone as it increases bleeding without improving outcomes 1

PAD with Coexisting Indications for Anticoagulation

1. PAD with Atrial Fibrillation:

   • For patients without prior intervention or with prior surgical repair: Stop all antiplatelet therapy and use OAC alone (DOAC preferred) 1
   • After endovascular intervention/stenting (within 1-3 months): Continue or switch to single antiplatelet therapy (clopidogrel preferred) plus OAC (DOAC preferred) 1
   • After standard DAPT duration post-intervention (usually 1-3 months): Stop all antiplatelet therapy and use OAC alone 1

2. PAD with Venous Thromboembolism (VTE):

   • DOACs are preferred over vitamin K antagonists for VTE treatment 1
   • After endovascular or surgical revascularization: Adding single antiplatelet therapy to anticoagulation is reasonable if not at high bleeding risk 1

Evidence Quality and Considerations

The recommendations are primarily based on the 2024 ACC/AHA guideline for PAD management 1 and the 2021 ACC expert consensus 1, which represent the most recent and highest quality evidence available.

Key findings from the evidence:

• Full-intensity anticoagulation with DOACs or warfarin for PAD alone has consistently shown increased bleeding risk without improving cardiovascular outcomes 1
• The COMPASS trial demonstrated that low-dose rivaroxaban (2.5 mg twice daily) plus low-dose aspirin reduced MACE and MALE compared to aspirin alone, but with increased bleeding risk 1
• When PAD coexists with atrial fibrillation, DOACs are preferred over warfarin 1
• Recent meta-analyses suggest DOACs may have lower rates of major limb events compared to vitamin K antagonists in PAD patients with atrial fibrillation 2

Clinical Application Algorithm

1. Assess if patient has another indication for anticoagulation:

   • If YES (atrial fibrillation, VTE): Use DOAC at standard dosing
   • If NO: Do not use standard-dose DOACs

2. Determine ischemic and bleeding risk:

   • High ischemic/low bleeding risk: Consider low-dose rivaroxaban (2.5 mg BID) plus aspirin
   • Other scenarios: Use single antiplatelet therapy

3. Consider timing of revascularization:

   • Recent endovascular intervention (<3 months): May need DAPT or SAPT+DOAC if another indication exists

   • 3 months post-intervention: Can typically reduce to SAPT or OAC alone if indicated

Common Pitfalls to Avoid

• Using full-intensity oral anticoagulation for PAD alone - this increases bleeding without improving outcomes
• Continuing dual antiplatelet therapy beyond necessary duration after revascularization
• Failing to distinguish between low-dose rivaroxaban (2.5 mg BID) for vascular protection versus full anticoagulant doses
• Not adjusting therapy based on bleeding risk and comorbidities

Remember that the evidence strongly cautions against using standard-dose DOACs for PAD management unless another indication exists, while supporting the use of antiplatelet therapy with or without low-dose rivaroxaban based on risk stratification.