What is Eliquis (apixaban) used for?

Eliquis (Apixaban) Uses

Eliquis (apixaban) is a direct factor Xa inhibitor primarily indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, for prophylaxis of deep vein thrombosis following hip or knee replacement surgery, and for treatment and reduction of recurrent deep vein thrombosis and pulmonary embolism. 1

Primary Indications

Stroke Prevention in Atrial Fibrillation

• Apixaban is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation 1
• It has demonstrated both noninferiority and superiority to warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (HR 0.79; 95% CI, 0.66–0.95) 2
• The benefit appears more pronounced in reducing hemorrhagic stroke (49% reduction) compared to ischemic stroke (8% reduction) 2

Venous Thromboembolism (VTE) Management

• Prophylaxis of deep vein thrombosis (DVT) in patients who have undergone hip or knee replacement surgery 1
• Treatment of established DVT and pulmonary embolism (PE) 1
• Reduction in the risk of recurrent DVT and PE following initial therapy 1, 3

Dosing Considerations

Standard Dosing

• For atrial fibrillation: 5 mg twice daily is the standard dose 2
• Dose reduction to 2.5 mg twice daily is recommended for patients meeting at least two of the following criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 2
• For VTE prophylaxis after orthopedic surgery: 2.5 mg twice daily 4

Special Populations

• Avoid use in patients with severe renal impairment (CrCl <15 mL/min) 5, 6
• Use with caution in patients with hepatic impairment (transaminases >2 times upper limit of normal or total bilirubin >1.5 times upper limit of normal) 5, 6
• Not recommended for patients with artificial heart valves 1
• Not recommended for patients with antiphospholipid syndrome with positive triple antibody testing and history of blood clots 1

Clinical Evidence and Efficacy

ARISTOTLE Trial (Atrial Fibrillation)

• In the ARISTOTLE trial (18,201 patients), apixaban demonstrated superiority over warfarin in preventing stroke or systemic embolism (1.27% vs 1.60% per year) 2
• Secondary endpoints also favored apixaban:
  • Lower mortality (3.52% vs 3.94%) 2
  • Reduced major bleeding (2.13% vs 3.09%) 2
• Consistent treatment effects were observed across various subgroups including those on concurrent aspirin, prior warfarin users, and patients with prior stroke or TIA 2

AMPLIFY Trials (VTE Treatment)

• Apixaban has demonstrated noninferiority to standard treatment (enoxaparin/warfarin) for acute VTE treatment with significantly lower bleeding risk 3
• In extended treatment (AMPLIFY-EXT), apixaban was significantly more effective than placebo in preventing recurrent VTE 3

Safety Considerations

Bleeding Risk

• Like all anticoagulants, apixaban carries a risk of bleeding which can be serious and rarely fatal 1
• However, it has demonstrated a favorable bleeding profile compared to warfarin 3, 7
• Increased bleeding risk when used with other medications that affect hemostasis, including:
  • Aspirin or aspirin-containing products
  • NSAIDs
  • Other anticoagulants
  • SSRIs/SNRIs 1

Perioperative Management

• Discontinue apixaban at least 3 days before procedures with high bleeding risk if CrCl >30 mL/min 5, 6
• Resume 24-72 hours after surgery when adequate surgical hemostasis is achieved 5
• Special caution needed with neuraxial anesthesia due to risk of spinal/epidural hematoma 1

Pharmacological Properties

Pharmacokinetics

• Oral bioavailability of approximately 50% 7
• Maximum concentration occurs 3-4 hours after administration 7
• Half-life of approximately 12 hours 7
• Multiple elimination pathways with approximately 27% renal excretion 7
• No clinically significant food interactions 7

Advantages Over Traditional Anticoagulants

• Predictable pharmacokinetics without need for routine monitoring 8, 9
• Fixed dosing regimen 8
• Fewer drug-drug and food interactions compared to warfarin 8, 7
• No need for bridging with parenteral anticoagulants 4

Common Pitfalls and Caveats

• No specific antidote was initially available, though andexanet alfa has been developed as a reversal agent 10
• Missing doses increases thromboembolism risk due to short half-life 2
• Transitioning from warfarin to apixaban requires careful management 2
• Avoid concomitant use with strong dual inhibitors of CYP3A4 and P-glycoprotein 1
• Monitor renal function as changes may require dose adjustment 5