What are the indications for Apixaban (apixaban)?

Indications for Apixaban

Apixaban is FDA-approved for five primary indications: stroke prevention in nonvalvular atrial fibrillation, DVT prophylaxis after hip or knee replacement surgery, treatment of DVT, treatment of pulmonary embolism, and prevention of recurrent DVT/PE. 1

FDA-Approved Indications

1. Stroke Prevention in Nonvalvular Atrial Fibrillation

• Apixaban reduces stroke and systemic embolism risk in patients with nonvalvular atrial fibrillation (hazard ratio 0.79 vs warfarin, 95% CI 0.66-0.95, demonstrating superiority). 2, 1
• The drug provides a 49% reduction in hemorrhagic stroke and 8% reduction in ischemic stroke compared to warfarin. 2
• Standard dosing is 5 mg twice daily, with dose reduction to 2.5 mg twice daily for patients meeting ≥2 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 2
• Apixaban demonstrated superiority over aspirin in patients unsuitable for warfarin therapy (55% risk reduction in stroke/systemic embolism). 3, 4

2. VTE Prophylaxis After Orthopedic Surgery

• Apixaban is indicated for DVT prophylaxis following hip or knee replacement surgery, which may lead to pulmonary embolism. 1
• The recommended dose for VTE prophylaxis after orthopedic surgery is 2.5 mg twice daily. 2

3. Treatment of Deep Vein Thrombosis

• Apixaban is approved for acute treatment of DVT. 1

4. Treatment of Pulmonary Embolism

• Apixaban is indicated for treatment of acute PE. 1

5. Prevention of Recurrent VTE

• Apixaban reduces the risk of recurrent DVT and PE following initial therapy. 1

Clinical Evidence Supporting Use

Atrial Fibrillation Evidence

• The ARISTOTLE trial (18,201 patients) demonstrated apixaban's superiority over warfarin with stroke/systemic embolism rates of 1.27% vs 1.60% per year (P=0.01 for superiority). 2
• Major bleeding was significantly reduced (2.13% vs 3.09% per year) compared to warfarin. 2
• All-cause mortality was reduced by 11% (3.52% vs 3.94%, P=0.047). 2
• Benefits were consistent in patients with moderate or severe valvular heart disease (excluding mechanical valves and significant mitral stenosis), showing no differential effect. 5

Guideline Recommendations

• The American Heart Association/American Stroke Association gives apixaban a Class I, Level of Evidence B recommendation for stroke prevention in nonvalvular atrial fibrillation. 3
• Apixaban is recommended alongside warfarin, dabigatran, and rivaroxaban, with selection based on risk factors, cost, tolerability, patient preference, potential drug interactions, and clinical characteristics. 3

Critical Safety Considerations

Contraindications and Warnings

• Avoid in severe renal impairment (CrCl <15 mL/min). 2
• Use with caution in hepatic impairment (transaminases >2× upper limit of normal or total bilirubin >1.5× upper limit of normal). 2
• Black box warning: Discontinuation increases stroke risk; ensure coverage with another anticoagulant when stopping apixaban. 3

Bleeding Risk Management

• Discontinue at least 3 days before high bleeding risk procedures if CrCl >30 mL/min. 2
• Bleeding risk increases when combined with aspirin, NSAIDs, or other medications affecting hemostasis. 2
• Triple therapy (apixaban + aspirin + clopidogrel) should be avoided whenever possible due to prohibitive bleeding risk. 6
• In acute coronary syndrome, apixaban added to dual antiplatelet therapy resulted in unacceptably high major bleeding rates. 7

Monitoring Considerations

• No routine anticoagulation monitoring is required due to predictable pharmacokinetics. 7, 8
• If hemoglobin drops, investigate bleeding source rather than empirically reducing dose, as underdosing increases both bleeding and thrombotic risks. 9

Mechanism and Pharmacology

• Apixaban is a highly selective, reversible, direct factor Xa inhibitor that inhibits free factor Xa, prothrombinase activity, and clot-bound factor Xa. 7
• Oral bioavailability is approximately 50%, with peak concentration at 3-4 hours and half-life of 12 hours. 8
• Elimination occurs via multiple pathways (metabolism, biliary excretion, direct intestinal excretion), with 27% renal clearance. 8