What is the recommended dose of Eliquis (apixaban) for stroke prevention in a patient with non-valvular atrial fibrillation and impaired renal function (creatinine 1.75)?

Apixaban Dosing for Stroke Prevention in a Patient with Creatinine 1.75

For a patient with non-valvular atrial fibrillation and a serum creatinine of 1.75 mg/dL, the recommended dose of Eliquis (apixaban) is 2.5 mg twice daily.

Dose Selection Rationale

• According to FDA labeling, apixaban dose should be reduced to 2.5 mg twice daily in patients with at least two of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1
• With a serum creatinine of 1.75 mg/dL, this patient meets one criterion for dose reduction, and if they have either age ≥80 years or weight ≤60 kg, the reduced dose would be indicated 1
• If the patient does not meet any other criteria (i.e., is younger than 80 years and weighs more than 60 kg), the standard dose of 5 mg twice daily would be recommended despite the elevated creatinine 2, 1

Clinical Evidence Supporting This Recommendation

• The ARISTOTLE trial, which established apixaban's efficacy for stroke prevention in non-valvular atrial fibrillation, included patients with impaired renal function and demonstrated that apixaban was superior to warfarin in reducing stroke and systemic embolism (HR 0.79; 95% CI, 0.66-0.95) 3
• Secondary analysis of the ARISTOTLE trial found consistent efficacy of apixaban in subjects with impaired renal function (estimated glomerular filtration rate <80 mL/min) 3
• Importantly, apixaban showed significantly greater reduction in major bleeding among those with more advanced renal dysfunction (estimated glomerular filtration rate ≤50 mL/min) compared to warfarin 3

Special Considerations for Renal Impairment

• Unlike other direct oral anticoagulants that require dose adjustments based solely on creatinine clearance, apixaban has more complex dosing criteria that consider multiple factors 4
• Apixaban has the lowest renal clearance (~27%) among direct oral anticoagulants, making it often preferred for patients with kidney impairment 5
• However, even with limited renal excretion, drug levels can accumulate in patients with severe renal impairment, potentially increasing bleeding risk 5

Monitoring Recommendations

• Regular monitoring of renal function is important, as fluctuations in kidney function are common in patients with atrial fibrillation and can necessitate dose adjustments 6
• Studies have shown that 29% of patients with atrial fibrillation after acute heart failure required apixaban dosage adjustment during a 6-month follow-up period due to changes in renal function 6
• Be vigilant for signs of bleeding, particularly at unusual sites such as pleural, pericardial, or intracranial spaces, especially in patients with compromised renal function 5

Common Prescribing Pitfalls to Avoid

• Research indicates that apixaban dosing in clinical practice is frequently inconsistent with labeling recommendations 7
• Inappropriate dose reduction often occurs based on age, weight, and serum creatinine levels, even when these factors don't meet the criteria for dose reduction 7
• One study found that 60.8% of patients receiving reduced-dose apixaban did not meet labeling criteria for dose reduction 7
• Conversely, some patients who should receive dose-reduced apixaban are prescribed the standard dose, potentially increasing bleeding risk 4

Algorithmic Approach to Dosing

1. Assess if patient meets criteria for dose reduction:

   • Serum creatinine ≥1.5 mg/dL (patient meets this with creatinine of 1.75)
   • Age ≥80 years
   • Body weight ≤60 kg

2. Determine appropriate dose:

   • If patient meets at least 2 of the above criteria: Use 2.5 mg twice daily 1
   • If patient meets only 1 criterion (serum creatinine 1.75): Use 5 mg twice daily 1

3. Monitor renal function periodically and adjust dose if additional criteria are met during follow-up 2, 6