How long should apixaban (eliquis) be withheld before surgery in a patient with chronic kidney disease (CKD)?

Apixaban Discontinuation Before Surgery in Patients with CKD

For patients with chronic kidney disease (CKD), apixaban should be withheld before surgery based on renal function and bleeding risk: 48-96 hours for high bleeding risk procedures with CrCl 30-50 ml/min, and at least 36 hours for low bleeding risk procedures with CrCl 15-30 ml/min. 1

Timing of Apixaban Discontinuation Based on CKD Stage and Bleeding Risk

For Procedures with Low Bleeding Risk:

• CrCl ≥80 ml/min: ≥24 hours before procedure
• CrCl 50-80 ml/min: ≥24 hours before procedure
• CrCl 30-50 ml/min: ≥24 hours before procedure
• CrCl 15-30 ml/min: ≥36 hours before procedure
• CrCl <15 ml/min: No official indication for use

For Procedures with High Bleeding Risk:

• CrCl ≥80 ml/min: ≥48 hours before procedure
• CrCl 50-80 ml/min: ≥48 hours before procedure
• CrCl 30-50 ml/min: ≥96 hours before procedure
• CrCl 15-30 ml/min: ≥48 hours before procedure
• CrCl <15 ml/min: No official indication for use

Determining Bleeding Risk

• Low bleeding risk procedures: Those with low frequency of bleeding and/or minor impact of bleeding
• High bleeding risk procedures: Those with high frequency of bleeding and/or important clinical impact

Important Considerations for CKD Patients

1. No bridging required: Bridging with LMWH/UFH is not recommended when discontinuing apixaban before surgery 1

2. FDA label guidance: The official FDA label states that apixaban should be discontinued at least 48 hours prior to elective surgery with moderate/high bleeding risk, and at least 24 hours prior to procedures with low bleeding risk 2

3. Resumption timing: Resume apixaban ≥24 hours after low bleeding risk procedures and 48-72 hours after high bleeding risk procedures, once adequate hemostasis has been established 1

4. Special considerations for advanced CKD:

   • Patients with CrCl <15 ml/min were excluded from major clinical trials
   • For patients with severely impaired renal function, consider measuring apixaban levels before surgery if available 1

5. Medication interactions: Consider longer discontinuation periods if the patient is taking concomitant medications that may affect apixaban metabolism, such as dronedarone, amiodarone, or verapamil 1

Clinical Evidence

Recent evidence from the ADIOS study showed that discontinuing apixaban for at least 48 hours before procedures resulted in clinically insignificant anticoagulation levels in most patients 3. However, this study did not specifically focus on CKD patients, who may have delayed clearance.

Studies comparing apixaban to warfarin in advanced CKD patients have shown similar or better safety profiles regarding bleeding risk 4, 5, 6, but these studies did not specifically address perioperative management.

Practical Approach

1. Assess the patient's current renal function (CrCl)
2. Determine the bleeding risk of the planned procedure
3. Follow the recommended discontinuation times based on CrCl and bleeding risk
4. Document the exact date and time of the last apixaban dose
5. Resume apixaban only after adequate hemostasis has been established

Pitfalls to Avoid

• Don't use standard discontinuation times for all CKD patients: Adjust based on renal function
• Don't bridge with heparin: This increases bleeding risk without additional benefit
• Don't resume apixaban too early: Wait until adequate hemostasis is achieved
• Don't forget to reassess renal function: CKD patients may have fluctuating renal function
• Don't overlook drug interactions: Concomitant medications may affect apixaban clearance

For patients with CKD G4-G5 (CrCl <30 ml/min), extra caution is needed as these patients were largely excluded from clinical trials, and apixaban has no official indication for use in patients with CrCl <15 ml/min 1, 7.