Which anticoagulants are contraindicated in patients with Chronic Kidney Disease (CKD)?

Anticoagulants Contraindicated in Chronic Kidney Disease

In patients with end-stage chronic kidney disease (CrCl <15 mL/min) or on dialysis, direct thrombin inhibitor dabigatran and factor Xa inhibitors rivaroxaban and edoxaban are contraindicated, while apixaban requires careful consideration with appropriate dose adjustments. 1

Contraindications by CKD Severity

End-Stage CKD (CrCl <15 mL/min) or Dialysis

• Dabigatran: Contraindicated by European Medicines Agency (EMA); not approved by FDA 1
• Rivaroxaban: Contraindicated by EMA; limited clinical data per FDA 1
• Edoxaban: Contraindicated by EMA; not approved by FDA 1
• Fondaparinux: Contraindicated (CrCl <20 mL/min) 1

Severe CKD (CrCl 15-30 mL/min)

• Dabigatran: Contraindicated by EMA; FDA allows 75mg BID (USA only) 1
• Fondaparinux: Contraindicated (CrCl <20 mL/min) 1

Recommended Anticoagulants in CKD

End-Stage CKD/Dialysis

• Warfarin: Remains the anticoagulant of choice with target INR 2.0-3.0 and good TTR >65-70% 1
• Apixaban: In USA only, 5mg BID is approved for hemodialysis patients 1

Severe CKD (CrCl 15-30 mL/min)

• Warfarin: First-line option with dose adjustment for INR 2.0-3.0 1
• Apixaban: 2.5mg BID (use with caution) 1
• Rivaroxaban: 15mg daily (use with caution) 1
• Edoxaban: 30mg daily (use with caution) 1

Dose Adjustments Required in Moderate CKD (CrCl 30-50 mL/min)

• Rivaroxaban: Reduce to 15mg daily with evening meal 1
• Enoxaparin: Dose reduction required; consider anti-Xa monitoring 1
• Bivalirudin: Reduce infusion rate to 1mg/kg/h 1
• Eptifibatide: Contraindicated if CrCl <30 mL/min 1
• Tirofiban: 50% reduction of bolus dose and infusion if CrCl <30 mL/min 1

Monitoring Recommendations

1. Renal function monitoring:

   • Evaluate before initiation of any anticoagulant
   • Monitor at least yearly in stable patients
   • More frequent monitoring if CrCl <60 mL/min (minimum frequency in months = CrCl/10) 1
   • Reassess during acute illness that may affect renal function

2. Anticoagulation monitoring:

   • For warfarin: Target INR 2.0-3.0 with TTR >65-70% 1
   • For UFH: Monitor aPTT closely, especially in severe CKD 1
   • For LMWH in severe CKD: Consider anti-Xa monitoring 1

Important Clinical Considerations

• Patients with CKD are often overdosed with anticoagulants, increasing bleeding risk 1
• Warfarin may promote vascular calcification in CKD patients, a specific concern due to excess calcium and phosphate body deposition 1
• Anticoagulant-related nephropathy occurs twice as frequently in CKD patients on warfarin compared to those without underlying renal disease 1
• For patients with moderate CKD, DOACs (with appropriate dose adjustments) have shown better safety profiles than warfarin in post-hoc analyses 2

Common Pitfalls to Avoid

1. Using unadjusted doses of renally cleared anticoagulants in CKD
2. Failing to regularly reassess renal function during anticoagulation therapy
3. Overlooking drug-drug interactions that may affect anticoagulant levels
4. Neglecting to consider the increased bleeding risk in CKD patients
5. Using contraindicated anticoagulants in severe CKD or dialysis patients

By following these guidelines and carefully selecting appropriate anticoagulants with proper dose adjustments based on renal function, clinicians can optimize the benefit-risk ratio for CKD patients requiring anticoagulation.