What are the considerations for using oral anticoagulants in patients with Chronic Kidney Disease (CKD)?

From the Guidelines

Oral anticoagulants in chronic kidney disease (CKD) should be carefully selected and dosed based on kidney function, with direct oral anticoagulants (DOACs) like apixaban generally preferred over warfarin when appropriate, as supported by the 2019 AHA/ACC/HRS guideline update 1. For patients with CKD requiring anticoagulation, the choice of anticoagulant and dosing strategy depends on the stage of CKD, with specific recommendations varying by CKD stage.

• In moderate CKD (eGFR 30-60 mL/min), apixaban 5 mg twice daily (reduced to 2.5 mg twice daily if age ≥80 years or weight ≤60 kg) is often recommended, as stated in the 2019 AHA/ACC/HRS guideline update 1 and the 2018 CHEST guideline 1.
• In severe CKD (eGFR 15-29 mL/min), apixaban with dose reduction may be used, while in dialysis-dependent patients, warfarin with target INR 2-3 remains common despite emerging data supporting apixaban, as discussed in the 2019 JACC review 1. Key considerations in the management of anticoagulation in CKD include:
• Regular monitoring of kidney function, as emphasized in the 2018 CHEST guideline 1 and the 2019 JACC review 1.
• Assessment of bleeding risk using tools like the HAS-BLED score, as recommended in the 2018 CHEST guideline 1.
• Drug interactions, particularly with medications that affect P-glycoprotein or CYP3A4 pathways, as noted in the 2019 JACC review 1. The benefit of anticoagulation must always be weighed against increased bleeding risk in CKD patients, with individualized decision-making based on indication, CKD stage, comorbidities, and patient preferences, as emphasized in the 2019 AHA/ACC/HRS guideline update 1 and the 2018 CHEST guideline 1.

From the FDA Drug Label

In pharmacokinetic studies, compared to healthy adult subjects with normal creatinine clearance, rivaroxaban exposure increased by approximately 44 to 64% in adult subjects with renal impairment. Nonvalvular Atrial Fibrillation Patients with Chronic Kidney Disease not on Dialysis In the ROCKET AF trial, patients with CrCl 30 to 50 mL/min were administered XARELTO 15 mg once daily resulting in serum concentrations of rivaroxaban and clinical outcomes similar to those in patients with better renal function administered XARELTO 20 mg once daily Patients with CrCl <30 mL/min were not studied, but administration of XARELTO 15 mg once daily is expected to result in serum concentrations of rivaroxaban similar to those in patients with moderate renal impairment Avoid the use of XARELTO in patients with CrCl <15 mL/min

The use of rivaroxaban in patients with Chronic Kidney Disease (CKD) requires careful consideration of the patient's renal function.

• For patients with CrCl 30 to 50 mL/min, a dose of 15 mg once daily is recommended.
• For patients with CrCl <30 mL/min, the use of rivaroxaban is not well studied, but a dose of 15 mg once daily is expected to result in similar serum concentrations to those with moderate renal impairment.
• The use of rivaroxaban is contraindicated in patients with CrCl <15 mL/min due to the increased risk of bleeding. 2

From the Research

Oral Anticoagulants in CKD

• The use of oral anticoagulants in patients with chronic kidney disease (CKD) has been a topic of interest in recent years, with several studies comparing the safety and efficacy of different anticoagulants in this population 3, 4, 5, 6.
• A systematic review and meta-analysis found that direct oral anticoagulants (DOACs) were associated with a reduced risk of stroke, systemic embolism, and venous thromboembolism compared to warfarin in patients with CKD, with a significant reduction in major bleeding events 5.
• Another study found that apixaban was associated with a significantly better risk reduction of stroke, systemic embolism, and venous thromboembolism, as well as major bleeding, compared to warfarin in patients with CKD stage 4-5 or on dialysis 6.
• The safety and efficacy of rivaroxaban and apixaban in patients with atrial fibrillation and stage 4-5 CKD or on dialysis have also been evaluated, with results suggesting that these agents are safe and at least as effective as warfarin in this population 4, 6.

Warfarin Dosing in CKD

• A study evaluating warfarin dose requirements in patients with CKD stages 3-5 and end-stage renal disease (ESRD) found that patients with reduced kidney function required lower warfarin doses, with an average daily dose of 4.3-4.8 mg compared to 5.6 mg in patients with normal kidney function 7.
• The time to reach a therapeutic international normalized ratio (INR) was also significantly lower in patients with CKD/ESRD compared to those with normal kidney function, suggesting that these patients may require less time to achieve a therapeutic INR 7.

DOACs in CKD

• The use of DOACs in patients with CKD has been shown to be effective and safe, with a reduced risk of stroke, systemic embolism, and venous thromboembolism compared to warfarin 3, 4, 5.
• DOACs have also been associated with a lower risk of major bleeding events compared to warfarin in patients with CKD, although the evidence is not uniform and more studies are needed to fully evaluate the safety and efficacy of these agents in this population 4, 5, 6.