What are the recommendations for stopping and starting Eliquis (apixaban) before and after surgery in a patient with atrial fibrillation (a-fib)?

Perioperative Management of Apixaban for Atrial Fibrillation

For patients on apixaban for atrial fibrillation undergoing surgery, stop apixaban 1 day (24 hours) before low-to-moderate bleeding risk procedures and 2 days (48 hours) before high bleeding risk procedures, then resume 24-48 hours after surgery once adequate hemostasis is achieved—bridging anticoagulation is not recommended. 1, 2

Preoperative Discontinuation Strategy

The timing of apixaban discontinuation depends entirely on the bleeding risk of the planned procedure and the patient's renal function:

Low-to-Moderate Bleeding Risk Procedures

• Stop apixaban 1 day (24 hours) before surgery 1, 2
• The last dose should be taken on the morning of the day before the procedure 1, 3
• This allows approximately 2-3 half-lives to elapse, resulting in minimal residual anticoagulant effect 3
• Examples include: endoscopy with biopsy, pacemaker implantation, non-coronary angiography, cholecystectomy 1, 3

High Bleeding Risk Procedures

• Stop apixaban 2 days (48 hours) before surgery 1, 2
• This corresponds to approximately 4 half-lives of drug elimination, resulting in approximately 6% residual anticoagulant effect at surgery 4
• Examples include: major orthopedic surgery, abdominal surgery, thoracic surgery, spinal/epidural anesthesia, complex endoscopy, transurethral prostate resection 1, 4

Renal Function Adjustments

For patients with moderate renal impairment (CrCl 30-50 mL/min):

• Extend the interruption period to 3-4 days before high bleeding risk surgery 4
• Apixaban has 25% renal clearance, and impaired renal function delays drug elimination 4
• Verify renal function before finalizing the interruption plan, as declining renal function can lead to drug accumulation and catastrophic bleeding 4

Minimal Bleeding Risk Procedures

• Do not interrupt apixaban for procedures with minimal bleeding risk where bleeding is easily controllable 1, 5
• Examples include: dental fillings, simple dental cleanings, cataract surgery 1, 5
• If timing flexibility exists, schedule the procedure 18-24 hours after the last dose to minimize peak anticoagulant effects 5

Bridging Anticoagulation: Not Recommended

Bridging with heparin or low molecular weight heparin is NOT recommended during the perioperative interruption period. 1, 4, 3

The rationale is clear:

• The rapid offset and rapid onset of action of apixaban obviates the need for heparin bridging 4, 3
• Bridging increases major bleeding risk (2-5%) without reducing stroke or systemic embolism 1, 4
• The PAUSE study demonstrated low 30-day postoperative rates of arterial thromboembolism (0.16%) with standardized perioperative apixaban management without bridging 3

Postoperative Resumption Strategy

Resume apixaban 24-48 hours (1-2 days) after surgery once adequate hemostasis is established. 1, 3, 2

Timing Based on Bleeding Risk

For low-to-moderate bleeding risk procedures:

• Resume apixaban 24 hours after surgery at the usual dose (5 mg twice daily or 2.5 mg twice daily based on dose reduction criteria) 3
• Ensure at least 6-24 hours have elapsed after the end of the procedure to allow sufficient wound hemostasis 3

For high bleeding risk procedures:

• Resume apixaban 48-72 hours after surgery 1, 4
• In procedures where resuming full-dose anticoagulation within 48-72 hours carries bleeding risk that outweighs thromboembolism risk, consider initiating post-operative thromboprophylaxis 6-8 hours after surgery and restarting apixaban at 48-72 hours 1
• Consider starting with a reduced dose (2.5 mg twice daily) for the first 2-3 days in patients at high thromboembolism risk, though this is not formally studied 4

Critical Safety Considerations

• Do not resume therapeutic-dose apixaban while an epidural catheter is in place to minimize bleeding complications 4
• Monitor for signs of bleeding after resumption 3
• If apixaban cannot be restarted promptly due to bleeding concerns, use mechanical thromboprophylaxis methods until anticoagulation can be safely resumed 3

Common Pitfalls and How to Avoid Them

Pitfall 1: Unnecessarily prolonged interruption

• Avoid holding apixaban longer than recommended, as this increases thromboembolic risk without additional bleeding benefit 3
• The FDA label specifies discontinuation at least 48 hours for moderate-to-high bleeding risk and 24 hours for low bleeding risk 2

Pitfall 2: Using bridging anticoagulation

• Do not bridge with heparin or LMWH—this increases bleeding without reducing stroke risk 1, 4
• The only exception might be in extremely high-risk thrombotic situations, requiring multidisciplinary consultation 1

Pitfall 3: Resuming too early after high-risk procedures

• For procedures with significant bleeding consequences (e.g., neurosurgery, spinal surgery), wait the full 48-72 hours before resuming 1, 4
• Premature resumption can lead to epidural hematoma and paralysis in spinal procedures 4

Pitfall 4: Failing to account for renal function

• Always verify creatinine clearance before surgery, especially in elderly patients 4
• Patients with CrCl 30-50 mL/min require extended interruption periods for high-risk procedures 4

Pitfall 5: Poor communication with surgical team

• Ensure clear documentation and communication about the timing of apixaban discontinuation and resumption 3
• Implement institutional guidelines for perioperative anticoagulation management to ensure consistent practice 1, 3

Practical Implementation Algorithm

1. Classify the procedure's bleeding risk (minimal, low-to-moderate, or high) 1
2. Check renal function (CrCl) to determine if extended interruption is needed 4
3. Stop apixaban:
   • 0 days (continue) for minimal bleeding risk 1, 5
   • 1 day for low-to-moderate bleeding risk 1, 2
   • 2 days for high bleeding risk (normal renal function) 1, 2
   • 3-4 days for high bleeding risk (CrCl 30-50 mL/min) 4
4. Do not bridge with heparin 1, 4
5. Resume apixaban:
   • 24 hours for low-to-moderate bleeding risk 3
   • 48-72 hours for high bleeding risk 1, 4
   • Only after adequate hemostasis is confirmed 2

This standardized approach, validated by the PAUSE study, resulted in major bleeding rates of only 1.35% and arterial thromboembolism rates of 0.16% at 30 days postoperatively 3.