Apixaban Use in Chronic Kidney Disease
Apixaban can be used in patients with chronic kidney disease with appropriate dose adjustments based on renal function, with non-vitamin K antagonist oral anticoagulants (NOACs) like apixaban being recommended over vitamin K antagonists (e.g., warfarin) for thromboprophylaxis in CKD G1-G4. 1
Dosing Recommendations Based on Kidney Function
- For patients with CKD stages G1-G3 (CrCl >30 mL/min), standard apixaban dosing can be used 1
- For patients with CKD stage G4 (CrCl 15-29 mL/min), apixaban should be prescribed at a reduced dose of 2.5 mg twice daily 2, 3
- Dose reduction to 2.5 mg twice daily is also required if the patient has at least two of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 3
- Apixaban is not officially indicated for use in patients with CrCl <15 mL/min who are not on dialysis 1, 3
Evidence Supporting Use in Advanced CKD
- Apixaban has the lowest renal clearance (27%) among NOACs, making it potentially more suitable for patients with impaired renal function 2, 4
- Recent studies have shown that apixaban has similar efficacy and potentially better safety profile compared to warfarin in patients with advanced CKD 5, 6
- A systematic review of patients with stage 4 and 5 CKD found that apixaban had equivalent efficacy to warfarin for prevention of stroke and systemic embolization, with an equivalent or better safety profile regarding bleeding events 5
Monitoring Recommendations
- Regular monitoring of renal function is essential in CKD patients on apixaban, with more frequent evaluation recommended for those with CrCl <60 mL/min 2
- For patients with CrCl <60 mL/min, renal function should be evaluated at least every 6-12 months 2
- For patients with CKD stage 4, monitoring renal function at least every 3 months is recommended 2
Special Considerations for Dialysis Patients
- In the United States, apixaban 5 mg twice daily is approved for use in chronic, stable dialysis-dependent patients, though plasma levels at this dose may be supratherapeutic 7
- For patients with end-stage renal disease on dialysis, apixaban 2.5 mg twice daily is often recommended based on pharmacokinetic studies showing this dose produces drug exposure similar to the standard dose in patients with normal renal function 7, 6
- The American College of Cardiology recommends apixaban 5 mg twice daily for ESRD patients on stable hemodialysis, with dose reduction to 2.5 mg twice daily if the patient is ≥80 years or weighs ≤60 kg 7
Safety Considerations
- A retrospective study comparing apixaban and warfarin in advanced CKD found similar bleeding rates at 3 months, but higher major bleeding rates with warfarin between 6 and 12 months 6
- Concomitant use of medications that may increase bleeding risk should be carefully evaluated 2
- When considering apixaban in CKD patients, assess both stroke risk (using CHA₂DS₂-VASc) and bleeding risk (using HAS-BLED) 2, 1
Clinical Pitfalls and Caveats
- Avoid using apixaban in patients with severe hepatic impairment (Child-Pugh class C) 3
- For patients transitioning from CKD stage 4 to stage 5 or dialysis, a careful reassessment of the anticoagulation strategy is warranted 2, 7
- There is limited evidence from randomized controlled trials specifically for CKD stage 5 and dialysis patients, as these populations were largely excluded from major clinical trials 5, 8
- When discontinuing apixaban before procedures, the timing depends on renal function and bleeding risk of the procedure - for CrCl 30-50 mL/min, discontinue ≥48 hours before high-risk procedures 1