For a patient on apixaban (Apixaban) who develops acute coronary syndrome (ACS), should aspirin (acetylsalicylic acid) 300 mg be given?

Aspirin Administration in ACS for Patients on Apixaban

Yes, give aspirin 162-325 mg loading dose immediately when a patient on apixaban develops acute coronary syndrome, but recognize this significantly increases bleeding risk and requires careful monitoring. 1

Immediate Management: Aspirin Loading Dose

For any patient presenting with ACS, aspirin should be administered immediately regardless of baseline anticoagulation status. 1 The recommended loading dose is:

• 162-325 mg orally (non-enteric coated, chewed when possible) for fastest onset of antiplatelet action 1
• This applies to both NSTE-ACS and STEMI presentations 1
• Administer as soon as ACS is suspected or confirmed, even in the prehospital setting 1

Critical Bleeding Risk Consideration

The combination of apixaban with aspirin substantially increases major bleeding risk, but the immediate thrombotic risk of untreated ACS outweighs bleeding concerns in the acute setting. 2, 3

Key bleeding data you must know:

• The APPRAISE-2 trial was terminated early due to excessive bleeding when apixaban was combined with antiplatelet therapy in ACS patients 2, 3
• Major bleeding rate with apixaban plus single antiplatelet therapy: 2.8% per year vs 0.6% with placebo 2
• Major bleeding rate with apixaban plus dual antiplatelet therapy: 5.9% per year vs 2.5% with placebo 2
• Concomitant aspirin use increased bleeding risk on apixaban from 1.8% to 3.4% per year 2

Maintenance Dosing Strategy

After the initial loading dose, transition to low-dose aspirin 75-100 mg daily (not 300 mg) to minimize bleeding while maintaining efficacy. 1

• Higher maintenance doses (>100 mg) increase bleeding without improving outcomes 1
• The 2025 ACC/AHA guidelines specifically recommend 75-100 mg daily maintenance for all ACS patients 1
• Avoid enteric-coated formulations during acute phase due to delayed absorption 1

P2Y12 Inhibitor Addition

Add a P2Y12 inhibitor (ticagrelor or clopidogrel) to create dual antiplatelet therapy, which is mandatory for ACS management. 1

Preferred regimen:

• Ticagrelor 180 mg loading dose, then 90 mg twice daily (preferred over clopidogrel) 1
• Alternative: Clopidogrel 300-600 mg loading dose, then 75 mg daily 1
• Continue for up to 12 months 1

Managing the Triple Therapy Dilemma

You now have a patient on triple antithrombotic therapy (apixaban + aspirin + P2Y12 inhibitor), which carries the highest bleeding risk. 4

Critical decision points:

1. Consider temporarily holding or reducing apixaban dose during the acute ACS period if bleeding risk is prohibitive, though guidelines do not provide explicit recommendations for this scenario 2

2. Strongly consider adding a proton pump inhibitor to all patients on this regimen to reduce gastrointestinal bleeding 1

3. Plan for early de-escalation strategy: After PCI (if performed), consider discontinuing aspirin after 1 month and continuing apixaban plus P2Y12 inhibitor only, though this is not standard practice and requires individualized assessment 5

Common Pitfalls to Avoid

• Do not withhold aspirin in ACS due to apixaban use - the immediate thrombotic risk of untreated ACS is greater than bleeding risk 1
• Do not use aspirin doses >100 mg for maintenance - this increases bleeding without improving efficacy 1
• Do not use enteric-coated aspirin initially - delayed absorption reduces acute effectiveness 1
• Do not forget PPI prophylaxis - essential for reducing GI bleeding on triple therapy 1

Monitoring Requirements

Close surveillance for bleeding complications is mandatory with this high-risk combination. 2, 4

• Monitor for signs of major bleeding (intracranial, gastrointestinal, requiring transfusion) 2
• Patients who experience bleeding have 24.7-fold increased risk of 30-day mortality 4
• Consider using radial (not femoral) access if PCI is performed to reduce vascular complications 5

Long-Term Strategy

After the acute ACS period and any revascularization, reassess the need for continued anticoagulation versus antiplatelet therapy. 1

• If apixaban was for atrial fibrillation: Continue apixaban long-term, consider stopping aspirin after completing recommended DAPT duration 5
• If apixaban was for another indication: Discuss with cardiology regarding optimal long-term antithrombotic strategy 2
• Transition to single antiplatelet therapy (aspirin or P2Y12 inhibitor) plus apixaban when appropriate, typically after 12 months 1