What is the recommended apixaban regimen for stroke prevention in non‑valvular atrial fibrillation, including dose adjustments and contraindications?

Apixaban for Stroke Prevention in Nonvalvular 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 reserved only for patients meeting at least two of three specific criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1

Standard Dosing Regimen

• The standard dose is apixaban 5 mg orally twice daily for stroke prevention in patients with nonvalvular atrial fibrillation. 1
• 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). 2, 3
• Apixaban also reduced major bleeding by 31% compared to warfarin (2.13% vs 3.09% per year). 2
• No loading dose or bridging anticoagulation is required when initiating therapy. 4

Dose Reduction Criteria: The "2-of-3 Rule"

Reduce to 2.5 mg twice daily ONLY when the patient meets at least TWO of the following three criteria: 1

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL

Critical pitfall: Inappropriately reducing the dose when only one criterion is met leads to underdosing and increased thromboembolic risk. 2, 5 Real-world data show that 60.8% of patients receiving reduced-dose apixaban do not meet labeling criteria for dose reduction. 5

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. 4
• 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
• Contraindication: Apixaban is contraindicated in patients with CrCl <15 mL/min who are NOT on dialysis. 4, 1
• Assess renal function before starting and at least annually thereafter, with more frequent monitoring if CrCl 30-50 mL/min. 4

Guideline Recommendations and Evidence Quality

• The 2021 AHA/ASA guidelines give apixaban a Class I, Level B-R recommendation for stroke prevention in nonvalvular atrial fibrillation, recommending it in preference to warfarin. 6
• Direct oral anticoagulants (DOACs) including apixaban should not be used in patients with moderate-to-severe mitral stenosis or mechanical heart valves. 6
• The recommendation applies regardless of whether the AF pattern is paroxysmal, persistent, or permanent. 6

Switching Between Anticoagulants

From warfarin to apixaban: 1

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

From apixaban to warfarin: 1

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

From other DOACs to apixaban: 1

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

Perioperative Management

• Discontinue apixaban at least 48 hours prior to elective surgery or invasive procedures with moderate or high bleeding risk. 1
• Discontinue at least 24 hours prior to procedures with low bleeding risk or where bleeding would be easily controlled. 1
• Bridging anticoagulation during the 24-48 hours after stopping apixaban is not generally required. 1
• Restart apixaban after procedures as soon as adequate hemostasis has been established. 1

Timing of Anticoagulation After Stroke

• For TIA in the setting of nonvalvular AF: It is reasonable to initiate anticoagulation immediately after the index event (Class IIa, Level C-EO). 6
• For stroke at low risk for hemorrhagic conversion: It may be reasonable to initiate anticoagulation 2-14 days after the index event (Class IIb, Level B-NR). 6
• For stroke at high risk of hemorrhagic conversion: It is reasonable to delay initiation beyond 14 days to reduce ICH risk (Class IIa, Level B-NR). 6

Key Safety Considerations

• No antidote is currently available for emergent reversal in the setting of hemorrhage, though reversal agents are being developed. 6, 4
• Due to the short half-life (approximately 12 hours), patients who miss doses may be at increased risk for thromboembolic events. 4, 7
• No routine coagulation monitoring is required. 4
• Monitor for signs of bleeding or thromboembolism clinically. 4

Spinal/Epidural Procedures

Epidural or spinal hematomas may occur in patients receiving neuraxial anesthesia or spinal puncture, potentially resulting in permanent paralysis. 1 Risk factors include:

• Use of indwelling epidural catheters
• Concomitant use of NSAIDs, antiplatelet agents, or other anticoagulants
• History of traumatic or repeated epidural/spinal punctures
• History of spinal deformity or surgery

Monitor patients frequently for neurological impairment; if compromise is noted, urgent treatment is necessary. 1

Common Prescribing Errors to Avoid

• Do not reduce the dose to 2.5 mg twice daily unless the patient meets at least TWO of the three dose-reduction criteria. Underdosing may lead to inadequate anticoagulation and increased stroke risk. 2, 5
• Do not assume a lower dose is always safer—inappropriate dose reduction increases thromboembolic risk without providing additional bleeding protection. 2
• Age, weight, and renal function are the most common factors leading to inappropriate dose reduction when they do not meet the "2-of-3" threshold. 5