What are the indications for Eliquis (apixaban) use in patients with non-valvular atrial fibrillation, deep vein thrombosis, or pulmonary embolism, considering factors such as age, weight, renal function, and bleeding risk?

Indications for Eliquis (Apixaban) Use

Eliquis is FDA-approved for five distinct indications: stroke prevention in nonvalvular atrial fibrillation, DVT prophylaxis after hip or knee replacement, treatment of DVT, treatment of PE, and reduction of recurrent DVT/PE risk. 1

Primary Indications

1. Nonvalvular Atrial Fibrillation (Stroke Prevention)

Apixaban is indicated for patients with nonvalvular atrial fibrillation who have at least one additional stroke risk factor. 2, 1

Standard dosing is 5 mg twice daily for most patients. 3, 4 The dose should be reduced to 2.5 mg twice daily only when patients meet at least 2 of the following 3 criteria: 2, 3

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL (133 μmol/L)

Key efficacy data: In the ARISTOTLE trial, apixaban demonstrated a 21% reduction in stroke or systemic embolism compared to warfarin (HR 0.79,95% CI 0.66-0.95), a 31% reduction in major bleeding, and an 11% reduction in all-cause mortality. 2, 3 This makes apixaban superior to warfarin across all three critical outcomes affecting morbidity and mortality.

Important caveat: Patients with only one dose-reduction criterion should receive the full 5 mg twice daily dose—underdosing these patients increases thromboembolic risk without additional safety benefit. 4, 5

2. Renal Function Considerations in Atrial Fibrillation

Apixaban can be used in patients with severe renal impairment (CrCl 15-30 mL/min), unlike dabigatran which is contraindicated below CrCl 30 mL/min. 2, 3

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 (not both criteria required in dialysis patients). 3

Contraindication: Apixaban should not be used in patients with CrCl <15 mL/min who are NOT on dialysis. 3, 4

3. Venous Thromboembolism (VTE)

Apixaban is indicated for: 1

• Prophylaxis of DVT following hip or knee replacement surgery
• Treatment of acute DVT
• Treatment of acute PE
• Reduction of recurrent DVT and PE risk after initial therapy

For VTE treatment: Initial dosing is 10 mg twice daily for 7 days, then 5 mg twice daily for continued treatment. 2 Unlike atrial fibrillation, there are no dose adjustment criteria based on age, weight, or renal function for VTE indications. 5

Contraindications and Special Populations

Valvular Heart Disease

"Nonvalvular atrial fibrillation" specifically excludes: 1, 6

• Mechanical prosthetic heart valves (absolute contraindication)
• Clinically significant mitral stenosis (absolute contraindication)

However, apixaban can be used in patients with: 6

• Moderate or severe valvular heart disease (other than mitral stenosis)
• Previous valve surgery (bioprosthetic valves)
• The ARISTOTLE trial included 26.4% of patients with moderate or severe valvular heart disease and showed consistent efficacy and safety

Bleeding Risk Considerations

Apixaban is preferred over warfarin in patients with elevated bleeding risk because it reduces major bleeding by 31% and intracranial hemorrhage by approximately 58% compared to warfarin. 2, 3 The European Heart Journal guidelines note that major bleeding appears lower with apixaban compared to other NOACs. 2

For patients deemed unsuitable for warfarin: Apixaban 5 mg twice daily is superior to aspirin, reducing stroke/systemic embolism by 55% without increasing major bleeding risk (AVERROES trial). 2

Practical Implementation

When to Choose Apixaban Over Other Anticoagulants

Apixaban should be strongly considered in patients with: 2

• Advanced age (≥75-80 years) due to lower bleeding risk
• Renal impairment (CrCl 15-50 mL/min) where dabigatran is contraindicated
• High bleeding risk (prior intracranial hemorrhage, falls risk)
• Poor warfarin control or inability to monitor INR

Monitoring Requirements

No routine coagulation monitoring is required. 3 However, assess: 3

• Renal function before initiation and at least annually (more frequently if CrCl 30-50 mL/min)
• Signs of bleeding or thromboembolism clinically
• Medication adherence (twice-daily dosing requires compliance)

Common Prescribing Errors to Avoid

Underdosing is more common than overdosing in clinical practice—only 79.3% of patients receive doses consistent with labeling. 7 Avoid these pitfalls:

• Do not reduce to 2.5 mg twice daily based on age alone—requires 2 of 3 criteria 2, 4
• Do not use in mechanical valves or significant mitral stenosis 1, 6
• Do not combine with dual antiplatelet therapy routinely—safety not established and bleeding risk substantially increased 2, 3
• Do not use if CrCl <15 mL/min without dialysis 3, 4