What anticoagulants can be used in patients with impaired renal function?

Anticoagulants for Patients with Renal Dysfunction

For patients with renal dysfunction, apixaban and rivaroxaban are the preferred anticoagulants, with specific dose adjustments based on the degree of renal impairment. 1

Anticoagulant Options by Degree of Renal Impairment

Mild to Moderate Renal Impairment (CrCl 30-80 mL/min)

• All NOACs (novel oral anticoagulants) can be used with appropriate dose adjustments 1
• NOACs show better safety profile compared to vitamin K antagonists (VKAs) in this population 2
• Recommended options:
  • Apixaban: 5 mg twice daily (reduce to 2.5 mg twice daily if two of the following: age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) 1
  • Rivaroxaban: 15-20 mg once daily (15 mg for CrCl 30-49 mL/min) 1
  • Edoxaban: 30-60 mg once daily (30 mg for CrCl 30-49 mL/min) 1
  • Dabigatran: 150 mg twice daily (outside US, 110 mg twice daily may be used in elderly or high bleeding risk) 1
  • VKAs (e.g., warfarin): Target INR 2-3 with good time in therapeutic range (TTR >65-70%) 1

Severe Renal Impairment (CrCl 15-29 mL/min)

• Rivaroxaban (15 mg once daily), apixaban (2.5 mg twice daily), and edoxaban (30 mg once daily) are approved in Europe for this population 1
• Apixaban may be preferable due to lowest renal clearance (27%) 1, 3
• VKAs can be used with close monitoring (TTR >65-70%) 1
• Dabigatran should be avoided in Europe (in US, 75 mg twice daily is approved based on pharmacokinetic simulations) 1

End-Stage Renal Disease (CrCl <15 mL/min or dialysis)

• Limited data exists for any anticoagulant in this population 1
• Well-managed VKAs (TTR >65-70%) may be considered 1
• In the US only, apixaban 5 mg twice daily is approved for chronic, stable dialysis patients, though plasma levels may be supra-therapeutic 1
• Reduced dose apixaban (2.5 mg twice daily) may achieve plasma levels similar to those in patients with normal renal function 1
• Avoid dabigatran and edoxaban 1

Parenteral Anticoagulants in Renal Dysfunction

Low Molecular Weight Heparins (LMWH)

• Dose reduction required for CrCl <30 mL/min or contraindicated depending on specific agent 1, 4
• Enoxaparin: Dose adjustment required if CrCl <30 mL/min 1

Unfractionated Heparin (UFH)

• Generally does not require dose adjustment in renal dysfunction 4
• Close monitoring recommended in severe renal impairment 4

Other Parenteral Options

• Fondaparinux: Contraindicated if CrCl <30 mL/min, though may be considered due to lower bleeding risk compared to enoxaparin 1
• Bivalirudin: Reduce infusion to 1.0 mg/kg/h if CrCl <30 mL/min; reduce to 0.25 mg/kg/h for hemodialysis patients 1

Glycoprotein IIb/IIIa Inhibitors

• Tirofiban: 50% dose reduction if CrCl <30 mL/min 1
• Eptifibatide: Reduce infusion to 1 mg/kg/min if CrCl <50 mL/min; contraindicated if CrCl <30 mL/min 1
• Abciximab: No specific dose adjustment, but careful evaluation of bleeding risk needed 1

Monitoring Recommendations

• Regular assessment of renal function, especially in NOAC users 1
• For VKAs, maintain TTR >65-70% 1
• For NOACs, adjust doses based on current renal function 1
• Consider drug-drug interactions that may increase bleeding risk 1

Special Considerations

• Apixaban shows better outcomes compared to warfarin in patients with renal dysfunction in recent studies 3, 5
• Avoid combining anticoagulants with antiplatelets, NSAIDs, or SSRIs when possible to reduce bleeding risk 1
• In patients requiring procedures, timing of anticoagulant discontinuation should be based on renal function 1
• For dabigatran, consider longer discontinuation periods (4-5 days before surgery for CrCl 30-50 mL/min) 1

Practical Algorithm for Anticoagulant Selection in Renal Dysfunction

1. Assess degree of renal impairment (CrCl using Cockcroft-Gault equation)
2. For CrCl 30-80 mL/min: Consider any NOAC with appropriate dose adjustment or well-managed VKA
3. For CrCl 15-29 mL/min: Consider apixaban (preferred), rivaroxaban, or well-managed VKA
4. For CrCl <15 mL/min: Consider well-managed VKA or apixaban (with caution)
5. For dialysis patients: Consider well-managed VKA; apixaban may be an alternative in stable patients
6. Regularly monitor renal function and adjust doses accordingly 1