In a patient after coronary artery bypass graft (CABG) surgery, when is apixaban appropriate, what dose should be used, and when should it be initiated?

Apixaban Use in Post-CABG Patients

Apixaban is appropriate in post-CABG patients only when there is a clear indication for anticoagulation (atrial fibrillation or venous thromboembolism), and should be initiated once hemodynamic stability is achieved and bleeding risk is acceptable, typically within 24-48 hours postoperatively for urgent indications.

Indications for Apixaban Post-CABG

Apixaban is indicated in post-CABG patients when anticoagulation is required for:

• Atrial fibrillation (AF): This is the most common indication, particularly for new-onset or pre-existing AF requiring stroke prevention 1
• Venous thromboembolism (VTE): For treatment of acute DVT/PE or extended secondary prevention 1
• Not indicated for graft patency alone: Apixaban and other anticoagulants are NOT recommended solely to prevent graft failure in post-CABG patients without other indications 1, 2

Critical Caveat

Mechanical heart valves are an absolute contraindication to apixaban - these patients require warfarin regardless of CABG status 1.

Dosing Regimens

For Atrial Fibrillation

• Standard dose: Apixaban 5 mg twice daily 1
• Reduced dose: Apixaban 2.5 mg twice daily if patient meets ≥2 of the following criteria:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL 1

For Acute VTE Treatment

• Initiation phase: Apixaban 10 mg twice daily for 7 days 1
• Maintenance phase: Apixaban 5 mg twice daily after completing the 7-day initiation dose 1
• Extended secondary prevention (after 6 months): Apixaban 2.5 mg twice daily may be used for long-term VTE prevention to reduce bleeding risk 1

Important: Complete the full initiation dose before transitioning to maintenance dosing, even in the post-CABG setting 1.

Timing of Initiation

Immediate Postoperative Period

• Aspirin remains the priority: Initiate aspirin 100-325 mg within 6 hours post-CABG and continue indefinitely (Class I recommendation) 3, 4
• Anticoagulation timing depends on indication urgency:
  • For urgent indications (acute VTE, high-risk AF): Initiate apixaban once hemodynamically stable and no active bleeding, typically 24-48 hours postoperatively 5
  • For non-urgent AF: Can delay initiation until bleeding risk is minimized 1

Post-Discharge Considerations

• If AF develops 2-3 days post-CABG (common in ~33% of patients): The benefit of early anticoagulation is uncertain, with conflicting evidence showing potential thromboembolic reduction versus increased bleeding risk 1
• For stable chronic coronary syndrome patients >1 year post-CABG: Anticoagulation can be initiated based on standard AF or VTE indications 1

Antiplatelet Therapy Management

First Year Post-CABG

• Continue aspirin <100 mg daily when initiating apixaban if <1 year post-CABG 1
• Triple therapy duration (apixaban + aspirin + P2Y12 inhibitor): Should be minimized; if high thrombotic risk/low bleeding risk, consider up to 30 days maximum 1
• Clopidogrel is preferred P2Y12 inhibitor when dual antiplatelet therapy is needed with anticoagulation 1

Beyond One Year Post-CABG

• Stop aspirin >1 year post-CABG when patient is on apixaban for AF or VTE 1
• Anticoagulation monotherapy is preferred after 6-12 months of dual antithrombotic therapy to reduce bleeding risk 1

Evidence Strength and Nuances

Supporting Evidence

• A pilot study demonstrated apixaban was safe and effective for postoperative AF after CABG, with significantly lower costs compared to warfarin when including bridging and monitoring expenses 5
• DOACs (including apixaban) are preferred over warfarin for non-cancer-associated thrombosis due to better compliance and no monitoring requirements 1

Contradictory Evidence

• The COMPASS-CABG trial showed that rivaroxaban (another DOAC) did not reduce graft failure rates post-CABG, reinforcing that anticoagulation should not be used solely for graft patency 6
• Anticoagulation with warfarin or rivaroxaban provides no protection against graft failure but may decrease long-term major adverse cardiac events in high-risk patients 2

Common Pitfalls to Avoid

• Do not use apixaban solely for graft patency: There is no evidence supporting anticoagulation for this indication alone 2, 6, 4
• Do not use reduced VTE doses for AF indication: The VTE maintenance dose (5 mg twice daily) is higher than what may be used for extended VTE prevention (2.5 mg twice daily) 1
• Do not bridge with LMWH: Bridging increases bleeding risk and should be avoided unless patient is at very high risk of recurrent VTE 1
• Monitor renal function: Apixaban clearance is 27% renal; dose adjustment is critical in renal impairment 7
• Avoid premature discontinuation of aspirin: Continue aspirin for at least the first year post-CABG even when on anticoagulation 1

Algorithm for Decision-Making

1. Establish clear indication: AF with CHA₂DS₂-VASc ≥2 or acute/chronic VTE
2. Assess bleeding risk: Ensure hemodynamic stability and no active bleeding
3. Determine timing: Initiate 24-48 hours post-op for urgent indications; can delay for non-urgent
4. Select appropriate dose: Use VTE initiation dose (10 mg BID × 7 days) for acute VTE; use AF dose (5 mg BID or 2.5 mg BID based on criteria) for AF
5. Manage antiplatelet therapy: Continue aspirin if <1 year post-CABG; stop if >1 year
6. Monitor and adjust: Reassess bleeding/thrombotic risk at 6-12 months and consider transitioning to monotherapy