What is the appropriate dosing for anticoagulants in older patients with impaired renal function?

Anticoagulant Dosing in Older Patients with Impaired Renal Function

For older patients with impaired renal function, anticoagulant doses should be reduced according to the specific agent and degree of renal impairment, with apixaban and warfarin being preferred options for severe renal impairment (CrCl <30 mL/min). 1

Assessing Renal Function in Older Patients

• Calculate creatinine clearance using the Cockcroft-Gault equation before initiating any anticoagulant 2
• Reassess renal function at least annually in stable patients and more frequently (2-3 times per year) in those with moderate to severe impairment 2
• Consider that older patients often have decreased renal function, altered pharmacokinetics, and increased bleeding risk 1

Anticoagulant Selection and Dosing by Renal Function

Moderate Renal Impairment (CrCl 30-59 mL/min)

1. Direct Oral Anticoagulants (DOACs):

   • Apixaban: 5 mg twice daily; reduce to 2.5 mg twice daily if age ≥80 years, weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1, 2
   • Rivaroxaban: 15 mg daily with food 1, 3
   • Dabigatran: 150 mg twice daily (110 mg twice daily outside US for patients ≥75 years) 1
   • Edoxaban: 30 mg daily 1

2. Parenteral Anticoagulants:

   • Enoxaparin: 1 mg/kg SC every 12 hours (standard dose) 1
   • Fondaparinux: 2.5 mg SC daily 1
   • Unfractionated Heparin (UFH): Weight-based dosing with close monitoring of aPTT 1

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

1. DOACs:

   • Apixaban: 2.5 mg twice daily (preferred DOAC in severe renal impairment) 1, 2
   • Rivaroxaban: 15 mg daily with food (use with caution) 1, 3
   • Dabigatran: 75 mg twice daily in US only (not recommended outside US) 1
   • Edoxaban: 30 mg daily (not universally recommended) 1

2. Parenteral Anticoagulants:

   • Enoxaparin: 1 mg/kg SC once daily (reduced frequency) 1
   • UFH: Consider as alternative to LMWH; standard dosing with careful monitoring 1
   • Fondaparinux: Avoid if CrCl <30 mL/min 1
   • Bivalirudin: Reduce to 1 mg/kg/h if CrCl <30 mL/min 1

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

1. Preferred Options:

   • Warfarin: Adjusted dose with target INR 2-3 and good TTR >65-70% 1
   • Apixaban: 5 mg twice daily or 2.5 mg twice daily if meeting dose reduction criteria (US only) 1, 2

2. Not Recommended:

   • Dabigatran: Avoid (80% renal clearance) 1
   • Rivaroxaban: Avoid 1, 3
   • Edoxaban: Avoid 1
   • Fondaparinux: Contraindicated 1

Special Considerations for Older Patients

• Start Low, Go Slow: Initiate at lower doses, especially for patients ≥75 years 1
• Bleeding Risk: Older patients have increased risk of bleeding complications, particularly gastrointestinal and intracranial bleeding 1
• Drug Interactions: Consider potential interactions with common medications in older adults (e.g., amiodarone, verapamil) 1
• Monitoring: More frequent monitoring of renal function and anticoagulant effect may be necessary 1, 2

Practical Recommendations

• For patients ≥75 years with AF and moderate renal impairment, apixaban is often preferred due to lower renal clearance (27%) compared to other DOACs 1, 2
• For patients requiring anticoagulation post-MI or for VTE with severe renal impairment, consider warfarin with good INR control or apixaban 1
• For patients on hemodialysis, warfarin with good TTR (>65-70%) is generally preferred, though apixaban may be considered in the US 1
• When using enoxaparin in older patients with renal impairment, consider anti-Xa monitoring to guide dosing 1

Common Pitfalls to Avoid

• Overestimation of renal function: Using weight or serum creatinine alone without calculating CrCl can lead to overdosing
• Failure to reassess renal function: Renal function may decline rapidly in older patients during acute illness
• Inappropriate DOAC selection: Not all DOACs are suitable for severe renal impairment
• Inadequate monitoring: Older patients with renal impairment require closer follow-up for bleeding complications
• Drug interactions: P-glycoprotein inhibitors can increase DOAC levels, especially in renal impairment

By following these guidelines and carefully selecting and dosing anticoagulants based on renal function, clinicians can optimize the balance between preventing thromboembolism and minimizing bleeding risk in older patients with impaired renal function.