Apixaban Dosing and Treatment Guidelines
Nonvalvular Atrial Fibrillation
The standard dose of apixaban for stroke prevention in 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, 2
Standard Dosing (5 mg Twice Daily)
- Patients with only ONE dose-reduction criterion should receive the full 5 mg twice daily dose, as demonstrated in the ARISTOTLE trial where this dosing showed consistent efficacy (HR 0.94 for stroke/systemic embolism) and safety (HR 0.68 for major bleeding) compared to warfarin 3
- The 5 mg twice daily regimen reduced stroke or systemic embolism by 21% (HR 0.79,95% CI 0.66-0.95) and major bleeding by 31% compared to warfarin 4, 5
- This dose is appropriate regardless of prior stroke history, as the benefit was consistent across all subgroups in ARISTOTLE 4
Dose Reduction Criteria (2.5 mg Twice Daily)
- Reduce to 2.5 mg twice daily ONLY when at least TWO of these are present: 1, 2
- 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 undertreated patients with increased thromboembolic risk 4, 5
Renal Impairment Considerations
- For CrCl >50 mL/min: Use standard 5 mg twice daily (unless meeting two dose-reduction criteria) 1
- For CrCl 15-50 mL/min: Apply the standard dosing algorithm based on the three dose-reduction criteria 1
- 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 1, 4
- For CrCl <15 mL/min NOT on dialysis: Apixaban is contraindicated 1, 2
- Dialysis has limited impact on apixaban clearance, and standard-dose apixaban (5 mg) showed lower risk of stroke/embolism and death compared to low-dose in dialysis patients 1
Combination with Antiplatelet Therapy
- After coronary intervention, use apixaban with clopidogrel (P2Y12 inhibitor of choice) WITHOUT aspirin after the initial periprocedural period to reduce bleeding while maintaining efficacy 1, 4
- For stable coronary disease without recent PCI, apixaban monotherapy is appropriate as adding antiplatelet therapy increases bleeding without clear benefit 4
Deep Vein Thrombosis and Pulmonary Embolism
Initial Treatment (First 7 Days)
For acute DVT or PE, initiate apixaban at 10 mg orally twice daily for the first 7 days of therapy. 1, 2
Maintenance Treatment (After 7 Days)
- After the initial 7-day period, reduce to 5 mg orally twice daily for the remainder of the treatment course 1, 2
- No parenteral bridging anticoagulation is required when starting apixaban 2
Extended/Secondary Prevention (After ≥6 Months)
- After completing at least 6 months of initial treatment, either 5 mg twice daily OR 2.5 mg twice daily can be used for extended secondary prevention 1, 2
- The 2.5 mg twice daily dose for extended therapy was studied specifically for secondary prevention and showed efficacy in reducing recurrent VTE 1
Cancer-Associated VTE
- Apixaban is NOT currently recommended for cancer-associated VTE due to insufficient data in this population 1
- Only 2.7% of patients in the AMPLIFY trial had cancer, making evidence inadequate for this indication 1
- LMWH (dalteparin 200 units/kg daily for 1 month, then 150 units/kg daily for months 2-6, or enoxaparin 1 mg/kg twice daily) remains preferred for cancer patients 1
Prophylaxis After Hip or Knee Replacement Surgery
The recommended dose is 2.5 mg orally twice daily, with the initial dose taken 12-24 hours after surgery. 2
Switching Between Anticoagulants
From Warfarin to Apixaban
- Discontinue warfarin and start apixaban when INR falls below 2.0 4, 2
- No bridging therapy is needed 4
From Apixaban to Warfarin
- Discontinue apixaban and begin BOTH parenteral anticoagulant AND warfarin at the time of the next scheduled apixaban dose 4, 2
- Continue parenteral anticoagulant until INR reaches therapeutic range 2
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, 2
Perioperative Management
Elective Surgery or Invasive Procedures
- Discontinue apixaban at least 48 hours prior to procedures with moderate or high bleeding risk 2
- Discontinue at least 24 hours prior to procedures with low bleeding risk 2
- Bridging anticoagulation during the 24-48 hours after stopping is not generally required 2
- Restart apixaban as soon as adequate hemostasis is established 2
Special Scenario: VTE Patients Requiring PCI
- If a patient is within the first 3 months of time-limited OAC therapy for VTE and requires elective PCI, defer the PCI until OAC therapy is completed 1
- The anticoagulation dose should be VTE-specific (higher than AF dosing): for maintenance VTE treatment, use 20 mg daily rivaroxaban or 5 mg twice daily apixaban, NOT the lower AF doses 1
Monitoring and Follow-Up
- No routine coagulation monitoring is required 4
- Assess renal function before starting and at least annually thereafter 4
- More frequent renal monitoring (every 3-6 months) if CrCl 30-50 mL/min or other risk factors for deterioration 4
- Monitor for signs of bleeding or thromboembolism clinically 4
Contraindications and Special Warnings
Absolute Contraindications
- Mechanical heart valves: All NOACs including apixaban are contraindicated based on RE-ALIGN trial outcomes 1
- CrCl <15 mL/min NOT on dialysis 1, 2
- Active pathological bleeding 2
Neuraxial Anesthesia Warning
- Epidural or spinal hematomas may occur with neuraxial anesthesia or spinal puncture, potentially causing permanent paralysis 2
- Risk factors include indwelling epidural catheters, concomitant NSAIDs/antiplatelet agents, history of spinal procedures, and spinal deformity 2
- Monitor patients frequently for neurological impairment; if compromise noted, urgent treatment is necessary 2