What are the indications for using aspirin (acetylsalicylic acid) and Eliquis (apixaban) together?

Indications for Aspirin and Eliquis (Apixaban) Combination Therapy

The combination of aspirin and apixaban is generally not recommended for routine stroke prevention in atrial fibrillation due to increased bleeding risk without additional efficacy benefits. The primary indications for this combination are limited to specific clinical scenarios involving concurrent cardiovascular conditions.

Primary Indications for Combination Therapy

1. Acute Coronary Syndrome (ACS) with Atrial Fibrillation:

   • Triple therapy (apixaban + aspirin + P2Y12 inhibitor like clopidogrel) is indicated for 1-6 months after ACS with stent placement in AF patients 1
   • After this initial period, dual therapy with apixaban and a single antiplatelet agent is recommended for up to 12 months 1

2. Elective Coronary Stenting in AF Patients:

   • Triple therapy for 1 month followed by dual therapy (apixaban + single antiplatelet) 1
   • Duration depends on bleeding risk versus thrombotic risk assessment

3. Recent Stroke/TIA with Concurrent Coronary Disease:

   • Limited duration combination therapy may be considered in patients with both conditions 2

Important Considerations and Cautions

Bleeding Risk

• Combining apixaban with aspirin significantly increases bleeding risk:
  • In ARISTOTLE trial, concomitant aspirin increased bleeding risk on apixaban from 1.8% to 3.4% per year 3
  • APPRAISE-2 trial was terminated early due to excess bleeding when apixaban was combined with antiplatelet therapy 3

Duration of Combination Therapy

• Combination therapy should be limited to the shortest necessary duration 1
• After the required period (based on indication), transition to:
  • Apixaban monotherapy for most AF patients
  • Single antiplatelet therapy for patients with coronary disease but without AF

Dosing Considerations

• Standard apixaban dosing for AF (5mg twice daily or 2.5mg twice daily for patients meeting dose reduction criteria)
• Low-dose aspirin (75-100mg daily) when combination is indicated

What NOT to Do

1. Do not use combination for routine stroke prevention in AF:

   • Apixaban alone is superior to aspirin for stroke prevention in AF 1, 4
   • Adding aspirin to anticoagulation increases bleeding without improving efficacy 1

2. Do not continue triple therapy longer than necessary:

   • Prolonged triple therapy substantially increases bleeding risk 1

3. Do not add aspirin to prevent recurrent embolic stroke in anticoagulated AF patients:

   • This is specifically contraindicated (Class III recommendation) 1

Algorithm for Decision-Making

1. Determine if patient has both AF requiring anticoagulation AND an indication for antiplatelet therapy:

   • Recent ACS or coronary stenting? → Consider time-limited combination
   • Stable coronary disease with AF? → Generally apixaban alone is sufficient 1

2. Assess bleeding risk:

   • High bleeding risk → Shorter duration of combination therapy
   • Low bleeding risk → Standard duration based on indication

3. Set clear timeline for de-escalation:

   • Document plan to discontinue aspirin at appropriate time point
   • Reassess regularly during combination therapy period

In summary, while apixaban and aspirin should generally not be used together for stroke prevention in AF, specific cardiovascular scenarios may warrant their temporary combination with careful monitoring and a clear plan for de-escalation to minimize bleeding risk.