Is Eliquis (apixaban) safe in patients with Chronic Kidney Disease (CKD) stage 4?

Apixaban Safety in CKD Stage 4

Apixaban is safe and preferred over warfarin in patients with CKD stage 4 (eGFR 15-29 mL/min), with appropriate dose reduction to 2.5 mg twice daily if the patient meets specific criteria. 1

Dosing Recommendations for CKD Stage 4

The appropriate dose adjustment for apixaban in CKD stage 4 is:

• Standard dose: 5 mg twice daily
• Reduced dose (2.5 mg twice daily) if patient has at least two of the following:
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL 1, 2

Evidence Supporting Apixaban in CKD Stage 4

The 2025 Kidney International guidelines strongly recommend NOACs, including apixaban, in preference to vitamin K antagonists (VKAs) for thromboprophylaxis in patients with CKD stages G1-G4 1. This recommendation is based on:

• Superior safety profile compared to warfarin
• Equivalent efficacy for prevention of stroke and systemic embolization
• Lower risk of major bleeding compared to warfarin 1, 3

A 2022 systematic review found that apixaban demonstrated equivalent efficacy to warfarin for prevention of stroke, systemic embolization, and recurrent venous thromboembolism in CKD stage 4 patients, while showing a better safety profile regarding bleeding events 3.

Monitoring Requirements

For patients with CKD stage 4 on apixaban:

• Monitor renal function at least every 3 months
• Reassess renal function during any acute illness that might affect kidney function 1
• Watch for signs of anticoagulant-related nephropathy, which occurs more frequently in CKD patients 1

Perioperative Management

For procedures requiring anticoagulation interruption in CKD stage 4 patients:

• Low bleeding risk procedures: Discontinue apixaban 48 hours before
• High bleeding risk procedures: Discontinue apixaban 96 hours before 1

Cautions and Considerations

1. Concomitant antiplatelet therapy substantially increases bleeding risk and should be used judiciously 1

2. While apixaban is approved for CKD stage 4, many landmark trials excluded patients with creatinine clearance <25 mL/min, so clinical experience is more limited than in patients with better renal function 3

3. A 2018 study showed that patients with advanced CKD taking apixaban had similar bleeding rates at 3 months compared to warfarin, but significantly lower major bleeding rates between 6-12 months (1.5% vs 8.4%, p<0.001) 4

4. The FDA label does not contraindicate apixaban in CKD stage 4, but does recommend dose adjustment based on specific patient characteristics 2

Common Pitfalls to Avoid

• Failing to adjust dose based on patient characteristics (age, weight, serum creatinine)
• Not monitoring renal function regularly
• Using standard doses in patients who meet criteria for dose reduction
• Adding antiplatelet therapy without careful consideration of bleeding risk

In conclusion, the evidence strongly supports the use of apixaban in CKD stage 4 patients with appropriate dose adjustment, with guidelines from Kidney International specifically recommending it over warfarin due to its favorable safety and efficacy profile.