What is the recommended use and dosage of Apixaban (apixaban) for patients with non-valvular atrial fibrillation or deep vein thrombosis/pulmonary embolism, considering factors such as impaired renal function?

Apixaban Dosing and Use in Nonvalvular Atrial Fibrillation and Venous Thromboembolism

Standard Dosing for 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 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

Evidence Supporting Standard Dosing

• The ARISTOTLE trial demonstrated that apixaban 5 mg twice daily reduced stroke or systemic embolism by 21% compared to warfarin (HR 0.79,95% CI 0.66-0.95), with a 31% reduction in major bleeding (2.1% vs 3.1% per year) 2, 3
• Apixaban also reduced intracranial hemorrhage by 58% compared to warfarin (0.2% vs 0.5%) 2
• All-cause mortality trended lower with apixaban compared to warfarin 2

Critical Dosing Algorithm

Apply this exact algorithm to determine the correct dose: 1

1. Start with 5 mg twice daily as the default
2. Count how many of these THREE criteria the patient meets:
   • Age ≥80 years
   • Body weight ≤60 kg
   • Serum creatinine ≥1.5 mg/dL
3. If ≥2 criteria present → reduce to 2.5 mg twice daily
4. If 0-1 criteria present → maintain 5 mg twice daily

Common Pitfall: Inappropriate Dose Reduction

The most critical error in clinical practice is reducing the dose to 2.5 mg twice daily when only ONE criterion is met—this undertreats patients and increases stroke risk. 3, 4

• Real-world data shows that 60.8% of patients receiving reduced-dose apixaban did not meet labeling criteria for dose reduction 5
• Clinicians inappropriately reduce doses based on age, weight, or renal function individually rather than requiring TWO criteria 5, 6
• Underdosing may lead to inadequate anticoagulation and increased thromboembolic events 4

Renal Function Considerations

Moderate to Severe Renal Impairment (CrCl 15-50 mL/min)

• For patients with CrCl >30 mL/min, apply the standard dosing algorithm above 7
• For patients with CrCl 15-30 mL/min, start with 5 mg twice daily and reduce to 2.5 mg twice daily ONLY if ≥2 dose-reduction criteria are met 3, 7
• Serum creatinine ≥1.5 mg/dL counts as ONE criterion toward dose reduction, but alone is insufficient 1

End-Stage Renal Disease on Hemodialysis

• Start with 5 mg twice daily 3, 7
• Reduce to 2.5 mg twice daily ONLY if age ≥80 years OR body weight ≤60 kg (note: only ONE criterion needed in dialysis patients, not two) 3, 7
• Clinical efficacy data in dialysis patients are limited, but pharmacokinetic modeling suggests similar drug levels to those in ARISTOTLE 1

Contraindications

• Apixaban should not be used in patients with CrCl <15 mL/min who are NOT on dialysis 2, 3
• Not recommended in severe hepatic impairment (Child-Pugh class C) 1

Dosing for Deep Vein Thrombosis and Pulmonary Embolism

Acute Treatment Phase

For acute DVT or PE treatment, use 10 mg orally twice daily for the first 7 days, then reduce to 5 mg twice daily for continued treatment. 1

• No dose adjustment needed for renal impairment in VTE treatment, including ESRD on dialysis 1
• This differs from the atrial fibrillation indication where dose reduction criteria apply 1

Extended Treatment for Recurrence Prevention

After completing at least 6 months of anticoagulation for DVT/PE, use 2.5 mg orally twice daily to reduce recurrence risk. 1

• This lower dose balances efficacy for preventing recurrent VTE against bleeding risk 1
• All patients receive 2.5 mg twice daily for extended prophylaxis regardless of age, weight, or renal function 1

Special Clinical Scenarios

Patients with Prior Stroke or TIA

• Apply the same dosing algorithm as for other atrial fibrillation patients—apixaban benefit is independent of prior stroke history 3, 7
• Recent data in subclinical atrial fibrillation shows a 7% absolute risk reduction in stroke over 3.5 years with apixaban versus aspirin in patients with prior stroke/TIA, compared to only 1% in those without prior events 8

Patients Requiring Antiplatelet Therapy

• If concurrent antiplatelet therapy is needed after PCI, use clopidogrel (NOT aspirin) with apixaban after a brief periprocedural period 3
• Triple therapy (apixaban + aspirin + P2Y12 inhibitor) increases bleeding risk without clear benefit and should be minimized 2
• The safety of combining apixaban with antiplatelet agents has not been well established 2

Switching Between Anticoagulants

From warfarin to apixaban: 1

• Discontinue warfarin
• Start apixaban when INR falls below 2.0
• No bridging therapy needed

From apixaban to warfarin: 1

• Discontinue apixaban
• Begin both 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
• Start apixaban at the time the next dose of the previous DOAC would have been due

Monitoring Requirements

• No routine coagulation monitoring is required 3
• Assess renal function before starting and at least annually thereafter 3, 7
• Monitor renal function more frequently if CrCl 30-50 mL/min or risk factors for deterioration present 7
• Evaluate body weight periodically, particularly in patients near the 60 kg threshold 7
• Assess clinically for signs of bleeding or thromboembolism 3

Perioperative Management

• Discontinue apixaban at least 48 hours prior to elective surgery with moderate or high bleeding risk 1
• Discontinue at least 24 hours prior to procedures with low bleeding risk 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 is established 1

Missed Dose Management

• If a dose is missed, take it as soon as possible on the same day 1
• Resume twice-daily administration 1
• Never double the dose to make up for a missed dose 1

Key Advantages Over Warfarin

• Superior efficacy in reducing stroke/systemic embolism (21% relative risk reduction) 2, 3
• Significantly lower rates of intracranial hemorrhage (58% relative risk reduction) 2
• Lower major bleeding rates (31% relative risk reduction) 3
• No need for routine INR monitoring 3
• Fewer drug-drug interactions 9
• Predictable pharmacokinetics across patient populations 9