What direct oral anticoagulants (DOACs) are approved for use in patients with severe impaired renal function (GFR <30)?

DOACs Approved for Use in Patients with GFR <30 mL/min

Apixaban is the only direct oral anticoagulant (DOAC) approved for use in patients with severe renal impairment (GFR <30 mL/min) at a reduced dose of 2.5 mg twice daily. 1

Evidence-Based Recommendations

Approved DOACs for Severe Renal Impairment

1. Apixaban (Eliquis)

   • Dose: 2.5 mg twice daily 1
   • Rationale: Least dependent on renal clearance (only 27% renal elimination) 1
   • FDA approved for use in severe renal impairment 1

2. Other DOACs (NOT approved for GFR <30 mL/min)

   • Dabigatran: Contraindicated in CrCl <30 mL/min 2
   • Rivaroxaban: Contraindicated in CrCl <30 mL/min 2
   • Edoxaban: Contraindicated in CrCl <30 mL/min 2

Renal Clearance of DOACs

DOAC	Renal Clearance	Use in GFR <30 mL/min
Apixaban	27%	Approved (2.5 mg BID)
Rivaroxaban	35%	Contraindicated
Edoxaban	50%	Contraindicated
Dabigatran	80%	Contraindicated

Clinical Considerations

Monitoring Requirements

• Monitor renal function at least every 3 months 1
• More frequent monitoring during acute illness 1
• Watch for signs of anticoagulant-related nephropathy (acute kidney injury) 1
• Assess for bleeding complications at each visit 1

Important Cautions

• All DOACs have higher blood levels and longer half-lives in patients with renal dysfunction 2
• Patients with renal dysfunction may also present with uremia-associated platelet dysfunction 2
• Dabigatran is the only DOAC that can be removed by hemodialysis 2

Special Populations

Dialysis Patients

• No DOACs are approved for use in dialysis patients 2
• For patients on dialysis, vitamin K antagonists (warfarin) remain the standard of care 2

Kidney Transplant Patients

• DOACs are not recommended for kidney transplant patients under immunosuppression with calcineurin inhibitors 3
• Conventional therapy with vitamin K antagonists is the only option for these patients 3

Practical Algorithm for DOAC Selection in Renal Impairment

1. Assess renal function accurately:

   • Use Cockcroft-Gault formula (as used in most DOAC trials) 2
   • Determine exact GFR/CrCl value

2. For patients with GFR <30 mL/min:

   • First choice: Apixaban 2.5 mg twice daily 1
   • If apixaban is contraindicated: Consider well-managed warfarin (TTR >65-70%) 1

3. For patients with GFR <15 mL/min or on dialysis:

   • Avoid all DOACs 2
   • Use warfarin with careful monitoring 2

Common Pitfalls to Avoid

1. Incorrect dosing: Registry data suggests inconsistent dosing of DOACs in renal impairment, which may lead to avoidable thromboembolic and bleeding events 4

2. Failure to reassess renal function: Renal function can deteriorate rapidly, especially in elderly patients or during acute illness 1

3. Drug interactions: Be aware of concomitant medications that affect DOAC levels, particularly P-glycoprotein inhibitors 1

4. Concomitant antiplatelet therapy: Should be avoided unless absolutely necessary due to substantially increased bleeding risk 1

By following these evidence-based recommendations, clinicians can appropriately select anticoagulation therapy for patients with severe renal impairment while minimizing risks of both thromboembolism and bleeding.