What are the guidelines for using Eliquis (apixaban) with aspirin (acetylsalicylic acid)?

Guidelines for Using Eliquis (Apixaban) with Aspirin

Combining apixaban and aspirin significantly increases bleeding risk and should generally be avoided unless there is a specific clinical indication requiring combination therapy, such as recent acute coronary syndrome or percutaneous coronary intervention. 1

General Principles

The European Society of Cardiology (ESC) and American College of Cardiology clearly state that bleeding events are more common when antithrombotic agents are combined, with no clear benefit observed in terms of stroke or death prevention 2, 1. This fundamental principle should guide clinical decision-making when considering combination therapy.

Specific Clinical Scenarios

1. Atrial Fibrillation (AF)

• Stable AF without vascular disease (>12 months after ACS/PCI):

  • Apixaban alone without antiplatelet therapy is recommended 2, 1
  • Adding aspirin provides no additional benefit but significantly increases bleeding risk 2
  • ESC guidelines explicitly state that antiplatelet drugs are not an alternative to oral anticoagulation and can lead to potential harm 2

• AF with recent ACS or PCI (<6 months):

  • Consider apixaban plus P2Y12 inhibitor (preferably clopidogrel) and discontinue aspirin after hospital discharge 2, 1
  • The AUGUSTUS trial demonstrated that apixaban plus a P2Y12 inhibitor without aspirin resulted in less bleeding than regimens including aspirin, with no significant difference in ischemic events 2

• AF with PCI (6-12 months post-procedure):

  • Continue either aspirin or clopidogrel with apixaban until 1 year post-PCI 1
  • After 12 months, discontinue antiplatelet therapy and continue apixaban alone 1

2. Peripheral Artery Disease

• For patients with infrainguinal bypass grafts:
  • Aspirin is beneficial for prosthetic grafts 2
  • For venous grafts, oral anticoagulation may be preferred over aspirin 2
  • The combination of aspirin and clopidogrel showed benefit specifically for prosthetic grafts below the knee 2

3. Embolic Stroke of Undetermined Source (ESUS)

• Recent evidence shows apixaban is not superior to aspirin in preventing new ischemic lesions in patients with ESUS, even in populations enriched with risk factors for cardioembolism 3

Risk Mitigation When Combination Therapy is Necessary

1. Minimize duration: Limit triple therapy (apixaban + dual antiplatelet therapy) to the shortest duration possible, preferably 30 days or less 1

2. Use lowest effective doses:

   • Use the lowest effective dose of aspirin (81 mg daily) 1
   • Consider apixaban dose reduction to 2.5 mg twice daily if patient meets criteria (≥2 of: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) 1

3. Gastric protection: Add a proton pump inhibitor for patients on combination therapy to reduce gastrointestinal bleeding risk 1

4. Close monitoring: Monitor patients on combination therapy frequently for bleeding complications 1

Perioperative Management

For patients requiring surgery while on apixaban and aspirin:

• Aspirin should typically be stopped 7-10 days before surgery unless specifically indicated 1
• For apixaban, timing of discontinuation depends on procedure bleeding risk and renal function:
  • Low bleeding risk procedures: May continue apixaban
  • High bleeding risk procedures: Stop apixaban 3 days before procedure if creatinine clearance >30 mL/min 2
  • Very high bleeding risk procedures (intracranial neurosurgery, neuraxial anesthesia): Stop apixaban up to 5 days prior 2

Special Populations

• Chronic Kidney Disease: Apixaban was superior to aspirin for stroke prevention in AF patients with stage III CKD (eGFR 30-59 mL/min), reducing primary events by 68% without significantly increasing major bleeding 4

• History of Stroke/TIA with Subclinical AF: Apixaban showed a 7% absolute risk reduction in stroke or systemic embolism over 3.5 years compared to aspirin, with only a 3% absolute increase in major bleeding 5

Common Pitfalls to Avoid

1. Unnecessary combination therapy: Don't combine apixaban and aspirin without a specific indication

2. Prolonged triple therapy: Extending triple therapy beyond 30 days significantly increases bleeding risk without additional benefit

3. Inadequate monitoring: Failure to monitor for bleeding complications in patients on combination therapy

4. Overlooking drug interactions: Be aware of medications that may affect apixaban levels (P-glycoprotein inhibitors, CYP3A4 inhibitors)

5. Inappropriate dosing: Using higher than necessary aspirin doses (>81 mg) when combination therapy is required

By following these evidence-based guidelines, clinicians can optimize the balance between thrombotic and bleeding risks when considering combination therapy with apixaban and aspirin.