Apixaban for Nonvalvular Atrial Fibrillation
For most patients with nonvalvular atrial fibrillation, prescribe apixaban 5 mg orally twice daily; reduce to 2.5 mg twice daily ONLY if the patient meets at least TWO of these three criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Standard Dosing Algorithm
The default dose is 5 mg twice daily for stroke prevention in nonvalvular atrial fibrillation, which demonstrated superiority over warfarin in the ARISTOTLE trial with a 21% reduction in stroke or systemic embolism (HR 0.79,95% CI 0.66-0.95) and a 31% reduction in major bleeding 2, 3, 4. This twice-daily regimen is necessary due to apixaban's 9-14 hour half-life 4.
Dose Reduction Criteria (Must Meet ≥2 of 3)
Reduce to 2.5 mg twice daily only when the patient has at least two of the following 1, 2:
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL (133 μmol/L)
Critical pitfall: Meeting only ONE criterion does not justify dose reduction 3. Real-world data shows that 60.8% of patients receiving reduced doses do not meet labeling criteria for dose reduction, with inappropriate underdosing driven by clinicians incorrectly reducing the dose based on a single factor 5. Underdosing patients who meet fewer than two criteria increases thromboembolic risk without proven bleeding benefit 3.
Renal Function Considerations
For severe renal impairment (CrCl 15-30 mL/min): Use the standard 5 mg twice daily dose unless the patient also meets the two-criterion rule for dose reduction 2, 4.
For end-stage renal disease on hemodialysis: Start with 5 mg twice daily, reducing to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg 2.
Contraindication: Do not use apixaban in patients with CrCl <15 mL/min who are NOT on dialysis 2, 4.
Apixaban demonstrated a 68% reduction in stroke events compared to aspirin in patients with stage III chronic kidney disease (mean eGFR 49 mL/min) without increasing major bleeding 6.
Initiation and Switching
Starting apixaban: No loading dose or bridging anticoagulation is required 2. Begin at the appropriate dose based on the criteria above 1.
Switching from warfarin: Discontinue warfarin and start apixaban when INR falls below 2.0 1, 2.
Switching to warfarin: Discontinue apixaban and begin both parenteral anticoagulant AND warfarin at the time of the next scheduled apixaban dose, continuing parenteral anticoagulation until INR reaches therapeutic range 1, 2.
Switching from other DOACs: Simply discontinue the other DOAC and start apixaban at the time the next dose would have been due 2.
Special Clinical Scenarios
Prior stroke or TIA: The standard dosing algorithm applies equally regardless of prior stroke history, as apixaban's benefit was consistent across subgroups with and without prior stroke in the ARISTOTLE trial 7, 2. In the AVERROES trial, apixaban was superior to aspirin for secondary prevention (2.5% vs 8.3% per year; NNT=16) 7.
Concurrent antiplatelet therapy: If coronary intervention is required, use apixaban with clopidogrel (without aspirin) after a brief periprocedural period to reduce bleeding while maintaining efficacy 2. For stable coronary disease without recent PCI, apixaban monotherapy is appropriate, as adding antiplatelet therapy increases bleeding without clear benefit 2.
Monitoring Requirements
No routine coagulation monitoring is required 2, 4. However, assess the following:
- Renal function before starting and at least annually, with more frequent monitoring if CrCl 30-50 mL/min 2, 4
- Body weight periodically 4
- Signs of bleeding or thromboembolism 2
Perioperative Management
Discontinue apixaban at least 48 hours prior to elective surgery with moderate or high bleeding risk, or at least 24 hours prior to procedures with low bleeding risk 1. Bridging anticoagulation during the 24-48 hours after stopping is not generally required 1. Restart apixaban as soon as adequate hemostasis is established 1.
Missed Dose Protocol
If a dose is missed, take it as soon as possible on the same day and resume twice-daily administration 1. Do not double the dose to make up for a missed dose 1.
Common Prescribing Errors to Avoid
The most frequent error is inappropriate dose reduction based on a single criterion rather than two 5, 8. In one study, only 79.3% of apixaban prescriptions were consistent with FDA labeling, with underdosing more common than overdosing 9. Age ≥80 years alone was the most common single factor incorrectly triggering dose reduction (56% of underdosed patients) 8. This underdosing compromises stroke prevention efficacy without proven safety benefit 3.