Do patients with a history of atrial fibrillation (AF) and peripheral arterial disease (PAD) with a critical ischemic event require both Aspirin (acetylsalicylic acid (ASA)) and apixaban?

Management of Anticoagulation in Atrial Fibrillation with PAD and Critical Ischemic Event

For patients with atrial fibrillation (AF) and peripheral arterial disease (PAD) with a critical ischemic event, oral anticoagulation with apixaban alone is recommended rather than combination therapy with aspirin plus apixaban. 1

Rationale for Anticoagulation Strategy

• Patients with AF require oral anticoagulation to reduce the risk of stroke and systemic embolism, with apixaban being a preferred agent due to its superior efficacy and safety profile compared to warfarin 2, 3
• Adding aspirin to anticoagulation increases bleeding risk without providing additional stroke prevention benefit in most AF patients 1
• For patients with PAD, single antiplatelet therapy is recommended to reduce the risk of major adverse cardiovascular events (MACE), but when AF is present, the need for anticoagulation takes precedence 2
• Full-intensity oral anticoagulation (such as apixaban) should not be combined with antiplatelet therapy unless there is a specific indication such as recent coronary stenting 2, 1

Evidence Supporting Apixaban Monotherapy in AF

• Apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality in patients with AF in the ARISTOTLE trial 4, 3
• The benefits of apixaban versus warfarin for stroke and systemic embolism prevention were consistent in patients with and without PAD 5
• Apixaban was also superior to aspirin alone for stroke prevention with similar bleeding rates in patients with AF who were unsuitable for warfarin in the AVERROES study 4, 3

Special Considerations for PAD Patients

• Patients with PAD and AF are at higher risk for both thromboembolic and bleeding events compared to those with AF alone 5
• While PAD typically warrants antiplatelet therapy, when AF is present with a critical ischemic event, oral anticoagulation should be the primary antithrombotic strategy 2
• The 2024 ACC/AHA guideline specifically states that in patients with PAD without another indication (such as AF), full-intensity oral anticoagulation should not be used, but this implies that when AF is present, anticoagulation is indicated 2

Potential Exceptions to Monotherapy

• After endovascular or surgical revascularization for PAD in patients requiring full-intensity anticoagulation for AF, adding single antiplatelet therapy may be reasonable if the patient is not at high risk of bleeding 2
• The duration of dual therapy (anticoagulant plus antiplatelet) should be minimized to reduce bleeding risk 1
• Recent coronary stenting would be an indication for temporary dual therapy with anticoagulation and antiplatelet therapy 1

Dosing and Monitoring Considerations

• The standard apixaban dose is 5 mg twice daily 1, 6
• Dose reduction to 2.5 mg twice daily is recommended for patients with at least 2 of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1, 6
• Regular monitoring of renal function is necessary as apixaban is partially excreted by the kidneys 1, 6

Bleeding Risk Management

• Patients on apixaban should be monitored for signs of bleeding, which may include unexpected bleeding, unusual bruising, red/pink/brown urine, or red/black stools 6
• The risk of bleeding is increased when apixaban is combined with other medications that affect hemostasis, including aspirin 6
• If a patient requires temporary interruption of apixaban for surgery or procedures, the timing should be carefully planned with their healthcare provider 6

In conclusion, for patients with both AF and PAD with a critical ischemic event, apixaban monotherapy provides the optimal balance of stroke prevention and bleeding risk reduction, unless there are specific indications for temporary dual therapy such as recent revascularization.