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

Apixaban (Eliquis) 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. 1

Evidence-Based Recommendations for Apixaban in CKD Stage 4

Apixaban has several advantages in CKD stage 4 patients:

• Least renally cleared (27%) among NOACs 1
• Approved by both FDA and European regulatory agencies for use in CKD stage 4 1, 2
• Requires dose reduction to 2.5 mg twice daily when at least two of the following are present: 2
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

Safety Profile in CKD Stage 4

Multiple studies demonstrate apixaban's favorable safety profile in CKD stage 4:

• The 2019 JACC review confirms that apixaban is associated with lower risk of major bleeding compared to warfarin in advanced CKD 1
• A meta-analysis of 43,850 patients showed apixaban was associated with a 58% reduction in major bleeding risk compared to warfarin (pooled OR 0.42; 95% CI 0.28-0.61) 3
• A 2020 study found no difference in major bleeding at 3 months between apixaban and warfarin, but significantly lower bleeding rates with apixaban between 6-12 months (1.5% vs 8.4%, p<0.001) 4
• A post-hoc analysis of ARISTOTLE trial patients with CrCl 25-30 mL/min showed apixaban caused less major bleeding (HR 0.34; 95% CI 0.14-0.80) compared to warfarin 5

Efficacy in CKD Stage 4

• Apixaban demonstrates similar efficacy to warfarin for stroke and systemic embolism prevention in CKD stage 4 3, 6, 4
• The 2018 European Heart Rhythm Association practical guide specifically states that apixaban may be preferable in patients with severe CKD 1
• The 2024 KDIGO guidelines recommend NOACs in preference to vitamin K antagonists for thromboprophylaxis in atrial fibrillation in CKD G1-G4 1

Monitoring Recommendations

For patients with CKD stage 4 on apixaban:

1. Monitor renal function more frequently (at least every 3 months) 1
2. Reassess renal function during any acute illness that might affect kidney function 1
3. Consider dose reduction to 2.5 mg twice daily if meeting criteria 2
4. Monitor for signs of bleeding regularly

Important Caveats and Considerations

• While randomized controlled trial data in CKD stage 4 is limited, observational data consistently shows better safety profile for apixaban versus warfarin 1, 3, 6
• Apixaban's pharmacokinetic profile in CKD stage 4 shows substantial overlap with patients having better renal function, supporting its use 5
• For procedures requiring anticoagulation interruption, apixaban should be discontinued 48 hours (low bleeding risk) to 96 hours (high bleeding risk) before the procedure 1
• Avoid in patients with severe hepatic impairment (Child-Pugh class C) 2

In conclusion, current evidence strongly supports apixaban as a safe option for anticoagulation in CKD stage 4 patients, with a more favorable bleeding risk profile compared to warfarin while maintaining similar efficacy for preventing thromboembolic events.