Is Eliquis (apixaban) safe to use in patients with Acute Kidney Injury (AKI)?

Use of Eliquis (Apixaban) in Patients with Acute Kidney Injury

Apixaban should be used with caution in patients with AKI, with consideration for anti-Xa level monitoring when available, as it may be associated with increased bleeding risk compared to patients without AKI. 1

Assessment of AKI Severity and Risk Factors

When considering apixaban use in a patient with AKI:

• Determine the severity of AKI and baseline renal function
• Assess bleeding risk factors (HAS-BLED score)
• Evaluate concomitant medications that increase bleeding risk, especially P2Y12 inhibitors which significantly increase bleeding risk (odds ratio = 5.9) 1

Evidence-Based Recommendations by AKI Severity

Mild to Moderate AKI

• Apixaban may be used with appropriate dose adjustments
• Consider dose reduction to 2.5mg twice daily if patient meets two of the following criteria:
  • Serum creatinine ≥1.5 mg/dL
  • Age ≥80 years
  • Body weight ≤60 kg 2

Severe AKI (CrCl <15 mL/min)

• Consider alternative anticoagulation strategies
• If apixaban is deemed necessary, use reduced dosing (2.5mg twice daily) with close monitoring 2
• Consider transitioning to unfractionated heparin for inpatients with severe AKI 3

Monitoring Recommendations

The 2023 study by Keller et al. demonstrated that anti-Xa level monitoring was associated with significantly lower rates of major bleeding compared to standard monitoring in patients with AKI receiving apixaban (2.1% vs 14%, p<0.01) 4. Therefore:

• When available, use anti-Xa level monitoring to guide therapy
• Target anti-Xa levels <100 ng/mL when transitioning to heparin infusion 3
• Monitor renal function frequently during treatment
• Assess for signs of bleeding regularly

Special Considerations

1. Anticoagulant-Related Nephropathy (ARN): Be aware that apixaban can potentially worsen AKI through ARN, which has been reported with apixaban use 5

2. Concomitant Medications: Avoid medications that increase bleeding risk when possible, particularly antiplatelet agents 1, 4

3. Benefit in Renal Impairment: The ARISTOTLE trial showed that patients with renal impairment had the greatest relative reduction in major bleeding with apixaban compared to warfarin (HR 0.50,95% CI 0.38-0.66) 6

Clinical Pitfalls to Avoid

1. Failure to monitor renal function: Renal function can rapidly change during AKI episodes

2. Overlooking drug interactions: P-glycoprotein and CYP3A4 inhibitors can increase apixaban levels

3. Not considering alternative anticoagulation: In severe AKI, unfractionated heparin may be safer due to its non-renal clearance and reversibility

4. Inadequate bleeding risk assessment: Patients with AKI on apixaban have shown higher than normal bleeding rates (7.8% in AKI vs 3.4% in non-AKI patients) 1

By following these evidence-based recommendations and monitoring strategies, apixaban can be used in selected patients with AKI with appropriate caution and dose adjustments.