Apixaban Dosing for Stroke Prevention in Atrial Fibrillation
For most patients with nonvalvular atrial fibrillation, apixaban 5 mg orally twice daily is the recommended dose, with dose reduction to 2.5 mg twice daily ONLY when at least TWO of the following criteria are met: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1, 2
Standard Dosing Algorithm
The standard dose is 5 mg orally twice daily for stroke prevention in nonvalvular atrial fibrillation. 1, 3 This dosing was established in the ARISTOTLE trial, which demonstrated a 21% reduction in stroke or systemic embolism compared to warfarin (HR 0.79,95% CI 0.66-0.95) and a 31% reduction in major bleeding. 4, 2
Dose Reduction Criteria
Reduce to 2.5 mg twice daily ONLY when the patient meets at least TWO of these three criteria: 1, 3, 2
- Age ≥80 years
- Body weight ≤60 kg
- Serum creatinine ≥1.5 mg/dL
Patients with only ONE dose-reduction criterion should receive the standard 5 mg twice daily dose. 5 A secondary analysis of ARISTOTLE demonstrated that patients with a single dose-reduction criterion who received 5 mg twice daily had similar efficacy (HR 0.94 for stroke) and safety (HR 0.68 for major bleeding) compared to warfarin as those with no dose-reduction criteria. 5
Renal Function Considerations
For patients with CrCl >30 mL/min, apply the standard dosing algorithm above. 2
For patients with CrCl 15-30 mL/min (severe renal impairment), start with 5 mg twice daily and reduce to 2.5 mg twice daily only if ≥2 dose-reduction criteria are met. 4, 2 The European Heart Rhythm Association guidelines specifically note that dose reduction to 2.5 mg twice daily occurs if CrCl 15-29 mL/min OR if two of the three standard criteria are met. 3
For patients with 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 (note: only ONE criterion needed in dialysis patients). 4, 2
Apixaban is contraindicated in patients with CrCl <15 mL/min who are NOT on dialysis. 1, 4
Treatment Duration
Apixaban should be continued indefinitely for stroke prevention in atrial fibrillation, as premature discontinuation increases the risk of thrombotic events. 1 The FDA black box warning emphasizes that if anticoagulation must be discontinued for reasons other than pathological bleeding, coverage with another anticoagulant should be considered. 1
Initiation and Switching
No loading dose or bridging anticoagulation is required when starting apixaban. 4
When switching from warfarin to apixaban: Discontinue warfarin and start apixaban when INR falls below 2.0. 1, 4
When switching from apixaban to warfarin: Discontinue apixaban and begin both parenteral anticoagulant AND warfarin at the time of the next scheduled apixaban dose, continuing parenteral anticoagulant until INR reaches therapeutic range. 1, 4
When switching 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. 4
Special Populations
For patients with prior stroke or TIA, use the same dosing algorithm, as apixaban's benefit is independent of prior stroke history. 4, 2 The ARISTOTLE trial included 19% of patients with previous stroke, and efficacy was consistent regardless of prior stroke status. 3
For patients requiring concurrent antiplatelet therapy after coronary intervention, use clopidogrel (not aspirin) with apixaban after a brief periprocedural period to reduce bleeding risk. 4, 2 The safety of combining apixaban with antiplatelet agents has not been well established and increases bleeding risk. 3, 4
Monitoring Requirements
No routine coagulation monitoring is required. 4
Assess renal function before starting and at least annually thereafter, with more frequent monitoring (every 3-6 months) if CrCl 30-50 mL/min or other risk factors for renal deterioration exist. 4, 2
Monitor body weight periodically, particularly in patients near the 60 kg threshold, as weight changes may affect dose-reduction criteria. 2
Assess clinically for signs of bleeding or thromboembolism at each visit. 4
Common Pitfalls to Avoid
Do not reduce the dose to 2.5 mg twice daily in patients with only ONE dose-reduction criterion. 5 This is a common error that results in underdosing and potentially inadequate stroke prevention. Analysis shows that patients with a single criterion benefit from the full 5 mg twice daily dose without excess bleeding. 5
Do not use apixaban in patients with CrCl <15 mL/min who are not on dialysis, as safety and efficacy have not been established. 1, 4
Do not double the dose to make up for a missed dose. 1 If a dose is missed, take it as soon as possible on the same day and resume twice-daily administration. 1