Does a patient with Acute Coronary Syndrome (ACS) require a full dose of aspirin (acetylsalicylic acid) if they are already on Eliquis (apixaban)?

Management of Aspirin Therapy in ACS Patients on Eliquis

For patients with Acute Coronary Syndrome (ACS) who are already on Eliquis (apixaban), a loading dose of aspirin (162-325 mg) should be given initially, followed by discontinuation of aspirin while continuing the P2Y12 inhibitor (preferably clopidogrel) along with Eliquis to minimize bleeding risk while maintaining antithrombotic protection. 1

Initial Management of ACS in Patients on Anticoagulation

When a patient on Eliquis develops ACS, the antithrombotic strategy requires careful consideration of both thrombotic and bleeding risks. The 2025 ACC/AHA guidelines provide clear direction:

1. Initial aspirin loading dose: All patients with ACS should receive an initial loading dose of aspirin (162-325 mg) regardless of whether they are on anticoagulation 1

2. Subsequent therapy: After the initial loading dose, the approach depends on time since ACS:

   • If <12 months since ACS: Stop aspirin, continue P2Y12 inhibitor (preferably clopidogrel), and maintain Eliquis 1
   • If >12 months since ACS: Most patients can be treated with Eliquis alone without antiplatelet therapy 1

Bleeding Risk Considerations

The combination of Eliquis with antiplatelet therapy significantly increases bleeding risk:

• In the APPRAISE-2 trial, the rate of major bleeding was 2.8% per year with apixaban plus single antiplatelet therapy versus 0.6% with placebo plus single antiplatelet therapy 2
• When dual antiplatelet therapy was added to apixaban, bleeding rates increased to 5.9% per year versus 2.5% with placebo 2
• In the ARISTOTLE trial, adding aspirin to apixaban nearly doubled the bleeding risk from 1.8% to 3.4% per year 2

Special Considerations Based on Clinical Scenario

For patients with recent PCI:

• <6 months post-PCI: Stop aspirin, continue clopidogrel, and maintain Eliquis 1
• 6-12 months post-PCI: Continue single antiplatelet therapy (either aspirin or clopidogrel) until 1 year post-PCI, along with Eliquis 1
• >12 months post-PCI: Eliquis alone is sufficient 1

For patients with prior CABG:

• <1 year post-CABG: Continue low-dose aspirin (<100 mg/day) with Eliquis 1
• >1 year post-CABG: Stop aspirin and continue Eliquis alone 1

Dosing Considerations

If aspirin is indicated (such as during the initial ACS presentation or in specific high-risk scenarios):

• Loading dose: 162-325 mg (non-enteric coated, chewed when possible) 1
• Maintenance dose: If aspirin must be continued, use the lowest effective dose (75-100 mg daily) to minimize bleeding risk 1, 3

Algorithm for Decision-Making

1. Assess time since ACS event:

   • Acute presentation: Give aspirin loading dose (162-325 mg)
   • Then assess:

2. If <12 months since ACS:

   • Stop aspirin
   • Continue P2Y12 inhibitor (preferably clopidogrel)
   • Continue Eliquis at appropriate dose

3. If >12 months since ACS:

   • Stop all antiplatelet therapy
   • Continue Eliquis alone

4. Consider exceptions for very high thrombotic risk:

   • Complex coronary lesions
   • Multiple or long stents
   • Left main or proximal LAD stenting
   • History of stent thrombosis
   • In these cases, consider continuing single antiplatelet therapy (preferably clopidogrel) with Eliquis if bleeding risk is low

Common Pitfalls to Avoid

1. Continuing dual antiplatelet therapy with Eliquis: This triple therapy approach dramatically increases bleeding risk and should be avoided or limited to the shortest necessary duration

2. Using high-dose aspirin maintenance: If aspirin must be continued, use the lowest effective dose (75-100 mg) as higher doses increase bleeding without additional benefit 3

3. Abrupt discontinuation of all antithrombotic therapy: This can trigger rebound thrombotic events; follow a structured approach to transitioning therapy 3

4. Failure to reassess bleeding and thrombotic risks: Regular reassessment is needed to determine when antiplatelet therapy can be safely discontinued