Should Apixaban (apixaban) be continued as an anticoagulant in a patient with impaired renal function (eGFR of 12) or switched to Low Molecular Weight Heparin (LMWH)?

From the Guidelines

For a patient with an eGFR of 12, apixaban should generally be discontinued and switched to low molecular weight heparin (LMWH). This recommendation is based on the most recent and highest quality study available, which highlights the concerns of using apixaban in patients with severe renal impairment due to the increased risk of bleeding complications 1. An eGFR of 12 falls below the threshold where apixaban's safety and efficacy are well established, making LMWH a safer alternative in this context.

Key Considerations for Switching to LMWH

• Discontinue apixaban and begin LMWH after 12 hours (or longer if renal function is severely impaired): This allows for a safe transition between anticoagulants, minimizing the risk of thrombotic events or bleeding complications.
• LMWH dosing should be adjusted based on weight and renal function: Typically, this requires a dose reduction in severe renal impairment. For example, enoxaparin might be reduced to 1 mg/kg once daily instead of twice daily, as indicated in guidelines for managing patients with severe renal dysfunction 1.
• Monitoring of anti-Xa levels: This is crucial for adjusting LMWH dosing in patients with severe renal impairment, providing a safety advantage by allowing for personalized anticoagulation management 1.

Rationale for the Recommendation

The decision to switch from apixaban to LMWH in a patient with an eGFR of 12 is primarily driven by the safety concerns associated with apixaban's use in severe renal impairment. Apixaban has partial renal clearance, and its use in patients with CrCl <30 mL/min is cautioned against due to the lack of sufficient data supporting its safe use in this population 1. In contrast, LMWH can be monitored and adjusted using anti-Xa levels, offering a more manageable anticoagulation strategy in patients with severe renal dysfunction.

Additional Recommendations

• Nephrology consultation: Given the severely reduced kidney function, consulting with a nephrologist is advisable to discuss the anticoagulation strategy and the potential need for dialysis.
• Careful monitoring: Patients switched to LMWH should be closely monitored for signs of bleeding or thrombosis, and their renal function should be regularly assessed to adjust the anticoagulation plan as necessary.

This approach prioritizes minimizing the risk of morbidity, mortality, and improving the quality of life for the patient by selecting an anticoagulant that can be safely managed in the context of severe renal impairment.

From the FDA Drug Label

The recommended dose of apixaban tablets is 2.5 mg twice daily in patients with at least two of the following characteristics:

• age greater than or equal to 80 years
• body weight less than or equal to 60 kg
• serum creatinine greater than or equal to 1.5 mg/dL

The patient's eGFR of 12 indicates severe renal impairment, but the label does not provide a direct recommendation for dose adjustment in this specific scenario. No conclusion can be drawn regarding whether apixaban should be continued or switched to LMWH in a patient with an eGFR of 12. 2

From the Research

Apixaban vs LMWH in Patients with eGFR of 12

• The decision to continue apixaban or switch to Low Molecular Weight Heparin (LMWH) in a patient with an estimated glomerular filtration rate (eGFR) of 12 should be based on the patient's individual risk factors and the potential benefits and risks of each treatment option 3.
• A systematic review and meta-analysis found that apixaban was associated with a significant reduction in venous thromboembolism (VTE) recurrence and major bleeding events compared to warfarin in patients with severe renal failure, including those with an eGFR < 30 mL/min/m2 3.
• However, the study also noted that more evidence is required due to the limited number of randomized controlled trials and prospective studies in this population 3.
• Another study found that LMWH should be adjusted to 50-65% and 75-85% of the original dose for patients with a creatinine clearance (CrCL) of <30 mL/min and 30-60 mL/min, respectively 4.
• In patients with end-stage renal disease (ESRD) on hemodialysis, LMWH anti-Xa levels have been used to guide the reversal of apixaban, but more evidence is needed to support this approach 5.

Considerations for Switching to LMWH

• The patient's renal function and the potential for LMWH dose adjustments should be carefully considered when deciding whether to switch from apixaban to LMWH 4.
• Trough concentration anti-Xa monitoring is preferred over peak monitoring for LMWH, aiming at a maximum concentration of 0.4 IU/mL for once-daily dosed tinzaparin and 0.5 IU/mL for twice-daily dosed enoxaparin and nadroparin 4.
• The patient's clinical status and the risk of VTE recurrence should also be taken into account when making this decision 3, 5.

Additional Factors to Consider

• The patient's overall health status, including the presence of any comorbidities, should be considered when deciding on the best treatment option 6, 7.
• Aerobic exercise has been shown to have a beneficial effect on kidney function and cardiovascular health in patients with chronic kidney disease (CKD) stages 3-4, but its impact on patients with an eGFR of 12 is unclear 6, 7.