Apixaban Dosing for Non-valvular Atrial Fibrillation
The standard recommended dose of apixaban for most patients with non-valvular atrial fibrillation is 5 mg taken orally twice daily, with a reduced dose of 2.5 mg twice daily for patients with at least two of the following characteristics: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Standard Dosing Protocol
- Standard dose: 5 mg twice daily
- Reduced dose: 2.5 mg twice daily if patient has at least two of:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
This dosing regimen is supported by high-quality evidence from the ARISTOTLE trial, which demonstrated that apixaban was superior to warfarin in preventing stroke or systemic embolism while causing less bleeding 2.
Efficacy and Safety Profile
Apixaban has demonstrated:
- 21% reduction in stroke or systemic embolism compared to warfarin
- 31% reduction in major bleeding compared to warfarin
- 11% reduction in all-cause mortality compared to warfarin 3
The benefits of apixaban are consistent across different patient subgroups, including those with renal impairment 3. In the ARISTOTLE trial, apixaban showed greater reduction in hemorrhagic stroke (49% reduction) compared to ischemic stroke (8% reduction) 2.
Special Populations and Considerations
Renal Impairment
- For patients with severe renal impairment (CrCl 15-29 mL/min), the dose should be reduced to 2.5 mg twice daily 3
- For patients with end-stage renal disease on hemodialysis, the recommended dose is 2.5 mg twice daily if they are either ≥80 years or ≤60 kg in weight 3
- Regular monitoring of renal function is essential for patients on apixaban 3
Single Dose-Reduction Criterion
Research from the ARISTOTLE trial demonstrated that patients with only one dose-reduction criterion (either advanced age, low body weight, or renal dysfunction) who received the standard 5 mg twice daily dose showed consistent benefits compared to warfarin, with similar safety profiles to those without any dose-reduction criteria 4.
Common Pitfalls in Apixaban Dosing
Inappropriate dose reduction: Studies have shown that 43-60% of patients receiving reduced-dose apixaban do not meet the criteria for dose reduction 5, 6. This "underdosing" occurs more frequently in older patients, despite not meeting the specific criteria for dose reduction 5.
Missing doses: If a dose is missed, it should be taken as soon as possible on the same day, and twice-daily administration should be resumed. The dose should not be doubled to make up for a missed dose 1.
Drug interactions: Approximately 3.2% of patients receiving apixaban take medications that could potentially interact with it through pharmacokinetic or pharmacodynamic mechanisms 7. Careful evaluation of concomitant medications is necessary.
Perioperative Management
- Discontinue apixaban at least 48 hours prior to elective surgery or invasive procedures with moderate/high bleeding risk 1
- Discontinue apixaban at least 24 hours prior to procedures with low bleeding risk 1
- Restart apixaban as soon as adequate hemostasis has been established 1
- Bridging anticoagulation during the 24-48 hours after stopping apixaban is not generally required 1
Switching Between Anticoagulants
- From warfarin to apixaban: Discontinue warfarin and start apixaban when INR is below 2.0 1
- From apixaban to warfarin: Consider starting both a parenteral anticoagulant and warfarin when the next dose of apixaban would have been taken, discontinuing the parenteral agent when INR reaches an acceptable range 1
- From apixaban to other anticoagulants: Discontinue apixaban and begin the new anticoagulant at the time of the next scheduled apixaban dose 1
By following these evidence-based dosing recommendations, clinicians can optimize the efficacy and safety of apixaban therapy for patients with non-valvular atrial fibrillation.