In which patient with symptomatic Peripheral Artery Disease (PAD) would initiation of aspirin (acetylsalicylic acid) 81 mg by mouth daily plus rivaroxaban (factor Xa inhibitor) 2.5 mg by mouth twice daily be most appropriate?

Appropriate Use of Aspirin Plus Rivaroxaban in Symptomatic PAD

Based on the 2024 ACC/AHA/Multisociety PAD Guidelines, the 62-year-old female with a past medical history of coronary artery disease would be the most appropriate candidate for initiation of aspirin 81 mg daily plus rivaroxaban 2.5 mg twice daily.

Rationale for Selection

The 2024 ACC/AHA/Multisociety PAD Guidelines specifically recommend this combination therapy for patients with symptomatic PAD:

• In patients with symptomatic PAD, low-dose rivaroxaban (2.5 mg twice daily) combined with low-dose aspirin is effective to reduce the risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) with a Class I recommendation 1
• This combination therapy is also recommended after endovascular or surgical revascularization for PAD to reduce MACE and MALE risk 1

Why Each Patient Is or Is Not Appropriate

62-year-old female with CAD (MOST APPROPRIATE)

• Has symptomatic PAD (as stated in the question)
• Has established coronary artery disease, which puts her at high risk for cardiovascular events
• No contraindications to either aspirin or rivaroxaban are mentioned
• The combination of low-dose rivaroxaban and aspirin has demonstrated significant reduction in both MACE and MALE in patients with CAD and PAD 2

67-year-old female with atrial fibrillation (NOT APPROPRIATE)

• Has atrial fibrillation with a CHA₂DS₂-VASc score of 4, which requires full anticoagulation
• The rivaroxaban dose of 2.5 mg twice daily is insufficient for stroke prevention in atrial fibrillation
• For patients with PAD who require full-intensity anticoagulation for another indication, adding single antiplatelet therapy is reasonable (Class 2a), but not the combination of low-dose rivaroxaban plus aspirin 1

55-year-old male with hemorrhagic stroke history (NOT APPROPRIATE)

• History of hemorrhagic stroke is a significant contraindication to combination antithrombotic therapy
• This patient has a high bleeding risk that would outweigh the potential benefits
• The combination of rivaroxaban and aspirin increases major bleeding compared to aspirin alone (HR 1.61,95% CI 1.12-2.31) 3

65-year-old male with recent pulmonary embolism (NOT APPROPRIATE)

• Recent pulmonary embolism requires therapeutic anticoagulation (not low-dose rivaroxaban)
• The 2.5 mg twice daily dose of rivaroxaban is specifically for cardiovascular risk reduction in PAD/CAD and is inadequate for treatment of recent pulmonary embolism
• For VTE treatment, rivaroxaban dosing should be 15 mg twice daily for 21 days followed by 20 mg once daily 4

Evidence-Based Approach to Antithrombotic Therapy in PAD

1. For symptomatic PAD patients with established CAD:

   • Low-dose rivaroxaban (2.5 mg twice daily) plus aspirin (81-100 mg daily) is recommended (Class I) 1
   • This combination provides dual pathway inhibition targeting both platelet aggregation and fibrin organization 5

2. For patients with contraindications to combination therapy:

   • Single antiplatelet therapy with either aspirin or clopidogrel is reasonable 6

3. For patients requiring full anticoagulation for other indications:

   • Use the appropriate therapeutic dose of anticoagulant for the primary indication
   • Consider adding single antiplatelet therapy if bleeding risk is not high 1

Important Considerations

• The combination of rivaroxaban plus aspirin increases bleeding risk compared to aspirin alone, but does not significantly increase fatal or critical organ bleeding 2
• Regular follow-up, at least annually, is recommended to assess clinical status, medication adherence, and cardiovascular risk factors 6
• Supervised exercise therapy remains a cornerstone of PAD management regardless of antithrombotic regimen 6

The evidence strongly supports that patients with symptomatic PAD and concomitant CAD, without major bleeding risk factors or need for full anticoagulation, derive the greatest benefit from the combination of low-dose rivaroxaban plus aspirin.