Are clopidogrel or apixaban associated with impaired renal function?

Apixaban and Clopidogrel in Relation to Renal Function

Neither clopidogrel nor apixaban is associated with causing impaired renal function, but apixaban requires careful consideration in patients with existing renal impairment due to its partial renal clearance. 1, 2

Renal Clearance and Considerations

Apixaban

• 27% renal clearance as unchanged drug 1
• Decreasing renal function results in modestly increased apixaban exposure:
  • AUC increases by approximately 44% in severe renal impairment 3
  • Cmax is not affected by renal impairment 3
• Dose adjustment considerations:
  • No dose adjustment required solely based on renal function 3
  • However, clinical guidelines recommend monitoring renal function at least yearly in patients on NOACs, and more frequently if renal function is impaired (CrCl ≤60 mL/min) 1

Clopidogrel

• No significant renal clearance 2
• No dose adjustment necessary in renal impairment 1, 2
• Limited information available on patients with severe renal dysfunction 2
• Studies show clopidogrel 75mg once daily is well tolerated in both moderate and severe renal failure 4

Clinical Outcomes in Renal Impairment

Apixaban

• In the ARISTOTLE trial, apixaban was more effective than warfarin in preventing stroke/systemic embolism and reducing mortality irrespective of renal function 5
• Apixaban was associated with less major bleeding events across all ranges of eGFRs 5
• The relative risk reduction in major bleeding was greater in patients with eGFR ≤50 mL/min (HR 0.50,95% CI 0.38-0.66) 5
• Worsening renal function (annual decrease in eGFR >20%) was associated with higher risk of stroke, bleeding, and mortality, but apixaban maintained its superior efficacy and safety compared to warfarin even in these patients 6

Clopidogrel

• The CURE trial showed clopidogrel's beneficial effect was observed across all tertiles of renal function 7
• Clopidogrel treatment increased the risk of minor bleeding in all renal function tertiles 7
• The risk of major bleeding with clopidogrel did not appear to be greatest in those with the lowest renal function 7

Monitoring Recommendations

Apixaban

• Monitor renal function at least yearly in all patients on apixaban 1
• For impaired renal function (CrCl ≤60 mL/min), more frequent evaluation is recommended:
  • Divide CrCl by 10 to obtain minimum frequency of renal function testing in months 1
  • Example: CrCl of 40 mL/min = testing every 4 months
• More frequent monitoring for patients with additional risk factors (older age, frailty, multiple comorbidities) 1
• Reassess during intercurrent acute illness (infections, heart failure) 1

Clopidogrel

• No specific renal monitoring requirements for clopidogrel 1, 2
• Standard clinical monitoring is sufficient 2

Clinical Implications

• When choosing between anticoagulants for patients with renal impairment, apixaban may be preferable to other NOACs due to its lower renal clearance (27% vs 35% for rivaroxaban, 50% for edoxaban, and 80% for dabigatran) 1
• For patients requiring antiplatelet therapy with renal impairment, clopidogrel does not require dose adjustment 1
• The combination of anticoagulants and antiplatelet agents increases bleeding risk and should be carefully balanced against potential benefits 1

Common Pitfalls to Avoid

1. Failing to assess baseline renal function before starting apixaban
2. Not adjusting monitoring frequency based on degree of renal impairment
3. Confusing acute renal failure with chronic kidney disease when assessing renal function
4. Not reassessing renal function during acute illness in patients on apixaban
5. Assuming that all NOACs have similar renal clearance profiles

Remember that while neither drug causes renal impairment, renal function affects apixaban's clearance and should be monitored appropriately to ensure safe and effective therapy.