What is the recommended dosage and usage of apixaban (a direct oral anticoagulant) for preventing stroke and treating deep vein thrombosis or pulmonary embolism in patients with non-valvular atrial fibrillation and impaired renal function?

Apixaban Dosing and Usage in Nonvalvular Atrial Fibrillation with Renal Impairment

Standard Dosing for Stroke Prevention

The recommended dose of apixaban for most patients with nonvalvular atrial fibrillation is 5 mg orally twice daily, with dose reduction to 2.5 mg twice daily ONLY when patients meet at least TWO of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1

Dose Reduction Criteria - Critical Algorithm

• Standard dose (5 mg twice daily): Use for patients with 0 or 1 of the dose-reduction criteria 2, 3
• Reduced dose (2.5 mg twice daily): Use ONLY when ≥2 criteria are met simultaneously 4, 1
  • Age ≥80 years
  • Body weight ≤60 kg
  • Serum creatinine ≥1.5 mg/dL

Renal Function Considerations

Apixaban can be used across a wide range of renal function, including severe impairment (CrCl 15-30 mL/min), with the standard dosing algorithm applied for patients with CrCl >15 mL/min not on dialysis. 3

• For patients with stage III chronic kidney disease (CrCl 30-60 mL/min), apixaban 5 mg twice daily reduced stroke by 68% compared to aspirin without significant increase in major bleeding 5
• Apixaban may be considered in patients with CrCl 15-30 mL/min who have at least one additional stroke risk factor, though safety and efficacy have not been fully established 4
• Apixaban is contraindicated in patients with CrCl <15 mL/min who are NOT on dialysis 3, 1

End-Stage Renal Disease on Hemodialysis

• Start with 5 mg twice daily 3
• Reduce to 2.5 mg twice daily ONLY if age ≥80 years OR body weight ≤60 kg (note: only ONE criterion needed in dialysis patients, not two) 3

Treatment of Deep Vein Thrombosis and Pulmonary Embolism

For acute DVT/PE treatment, apixaban dosing is 10 mg orally twice daily for the first 7 days, then 5 mg twice daily thereafter. 1

• This dosing regimen is independent of renal function for patients with CrCl >15 mL/min 6
• After at least 6 months of treatment, the dose for preventing recurrent DVT/PE is 2.5 mg twice daily 1

Clinical Efficacy Evidence

• In the ARISTOTLE trial, apixaban 5 mg twice daily demonstrated 21% reduction in stroke/systemic embolism compared to warfarin (HR 0.79,95% CI 0.66-0.95) 4, 2
• Major bleeding was reduced by 31% compared to warfarin (2.1% vs 3.1% per year) 4, 7
• Intracranial hemorrhage was reduced by 58% (0.2% vs 0.5% per year) 4
• All-cause mortality was reduced by 11% 7

Critical Pitfalls to Avoid

Inappropriately reducing the dose to 2.5 mg twice daily in patients who meet only ONE criterion (not two) may compromise stroke prevention efficacy and increase thromboembolic risk. 2

• Patients with normal renal function and normal weight who receive the reduced 2.5 mg dose are undertreated 2
• Do not assume a lower dose is always safer—underdosing increases stroke risk without providing additional bleeding protection 2
• Stage III CKD alone (without meeting two dose-reduction criteria) does not warrant dose reduction 5

Switching Between Anticoagulants

From Warfarin to Apixaban

• Discontinue warfarin and start apixaban when INR falls below 2.0 1
• No bridging therapy is needed 3

From Apixaban to Warfarin

• Discontinue apixaban and begin both parenteral anticoagulant AND warfarin at the time of the next scheduled apixaban dose 1
• Continue parenteral anticoagulant until INR reaches therapeutic range 1

From Other DOACs to Apixaban

• Simply discontinue the other DOAC and start apixaban at the time the next dose of the previous DOAC would have been due 3, 1

Monitoring Requirements

• No routine coagulation monitoring is required 3
• Assess renal function before starting and at least annually thereafter 3
• More frequent renal monitoring (every 3-6 months) if CrCl 30-50 mL/min or other risk factors for deterioration 3
• Evaluate for signs of bleeding or thromboembolism at each visit 3

Perioperative Management

• Discontinue at least 48 hours prior to elective surgery with moderate or high bleeding risk 1
• Discontinue at least 24 hours prior to procedures with low bleeding risk 1
• Bridging anticoagulation is not generally required 1
• Restart as soon as adequate hemostasis is established 1

Combination with Antiplatelet Therapy

• The safety and efficacy of combining apixaban with antiplatelet agents have not been established 4
• For patients requiring coronary intervention, apixaban with clopidogrel (without aspirin) after a brief periprocedural period reduces bleeding while maintaining efficacy 3
• Do not routinely combine apixaban with aspirin, as this increases bleeding without providing additional stroke protection in most atrial fibrillation patients 7