What are the uses of Eliquis (apixaban) for patients with vascular disease, particularly those with non-valvular atrial fibrillation, deep vein thrombosis, or pulmonary embolism, and how does the treatment dose vary for patients with impaired renal function or high risk of bleeding?

Uses of Eliquis (Apixaban) for Vascular Disease

Eliquis is FDA-approved for stroke prevention in nonvalvular atrial fibrillation, treatment and prevention of deep vein thrombosis and pulmonary embolism, and prophylaxis after hip or knee replacement surgery—these are the only evidence-based indications for vascular disease management. 1

FDA-Approved Indications for Vascular Disease

Stroke Prevention in Nonvalvular Atrial Fibrillation

• Standard dose: 5 mg orally twice daily for most patients with atrial fibrillation and at least one stroke risk factor 1
• Reduced dose: 2.5 mg twice daily when patients meet at least 2 of these 3 criteria: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL 1, 2
• Apixaban demonstrated superiority over warfarin in the ARISTOTLE trial, reducing stroke/systemic embolism by 21%, major bleeding by 31%, and all-cause mortality by 11% 3
• Apixaban showed 55% reduction in stroke compared to aspirin in patients unsuitable for warfarin therapy in the AVERROES trial 3

Deep Vein Thrombosis and Pulmonary Embolism Treatment

• Initial treatment: 10 mg orally twice daily for 7 days, then 5 mg twice daily for continued treatment 1
• Prevention of recurrence: 2.5 mg twice daily after completing at least 6 months of treatment for DVT/PE 1

DVT Prophylaxis After Orthopedic Surgery

• Dose: 2.5 mg orally twice daily, starting 12-24 hours after surgery 1
• Duration: 35 days for hip replacement, 12 days for knee replacement 1

Critical Dosing Considerations for Renal Impairment

Atrial Fibrillation Dosing Algorithm

• CrCl >50 mL/min: Use 5 mg twice daily unless 2 of 3 dose-reduction criteria are met 2
• CrCl 30-50 mL/min (moderate impairment): Continue 5 mg twice daily unless patient meets 2 of 3 dose-reduction criteria (age ≥80, weight ≤60 kg, creatinine ≥1.5 mg/dL) 2
• CrCl 15-30 mL/min (severe impairment): Use 2.5 mg twice daily with caution 2
• End-stage renal disease on hemodialysis: FDA recommends 5 mg twice daily, reduced to 2.5 mg twice daily only if age ≥80 years OR weight ≤60 kg 3, 2
• CrCl <15 mL/min not on dialysis: Apixaban should be avoided 2

Pharmacokinetic Advantage in Renal Disease

• Apixaban has only 27% renal clearance, making it safer in renal impairment compared to dabigatran (80% renal) or rivaroxaban (66% renal) 3, 2
• Calculate creatinine clearance using the Cockcroft-Gault equation, not eGFR, as this is what FDA labeling and clinical trials used 2

Common Prescribing Errors to Avoid

Underdosing Pitfall

• The most common error is reducing apixaban to 2.5 mg twice daily based on a single criterion (e.g., renal impairment alone) rather than requiring 2 of 3 criteria 2
• Studies show 9.4-40.4% of apixaban prescriptions involve inappropriate underdosing 2
• Do not reduce dose based solely on perceived bleeding risk without meeting formal criteria 2

Monitoring Requirements

• Reassess renal function at least annually, and every 3-6 months if CrCl <60 mL/min 2
• No routine INR monitoring is required with apixaban 3, 2

Perioperative Management

Preoperative Discontinuation

• High bleeding risk procedures: Stop apixaban at least 48 hours before surgery 1
• Low bleeding risk procedures: Stop apixaban at least 24 hours before surgery 1
• Bridging anticoagulation is not generally required during the 24-48 hour interruption period 1

Postoperative Resumption

• Restart apixaban as soon as adequate hemostasis is established 1
• For high bleeding risk procedures like cervical spine surgery, wait 24-72 hours postoperatively before restarting therapeutic anticoagulation 4
• If epidural catheter was placed, delay therapeutic anticoagulation until after catheter removal 4

Drug Interactions

Contraindicated Combinations

• Avoid concomitant use with combined P-glycoprotein and strong CYP3A4 inhibitors (ketoconazole, ritonavir, itraconazole) in patients receiving 5 mg twice daily—reduce to 2.5 mg twice daily if necessary 2
• Avoid use with rifampin and other strong CYP3A4 inducers 2

Safe Combinations

• Proton pump inhibitors do not significantly interact with apixaban 2
• Aspirin up to 162 mg daily was permitted in clinical trials, though combined use increases bleeding risk 3

Comparative Efficacy in Atrial Fibrillation

The table below summarizes apixaban's performance versus warfarin in the ARISTOTLE trial 3:

• Ischemic stroke: HR 0.92 (95% CI 0.74-1.13)
• Hemorrhagic stroke: HR 0.51 (95% CI 0.35-0.75)
• All-cause mortality: HR 0.89 (95% CI 0.80-0.998)
• Major bleeding: HR 0.69 (95% CI 0.60-0.80)
• Gastrointestinal bleeding: HR 0.89 (95% CI 0.70-1.15)

Apixaban demonstrated consistent benefits across subgroups including patients with prior stroke/TIA, concurrent aspirin use, and varying degrees of renal impairment 3

Limitations and Unresolved Issues

• No specific antidote exists for emergent reversal in hemorrhage (though andexanet alfa has since been developed) 3
• Unknown safety with thrombolytic therapy for acute ischemic stroke 3
• Short half-life (~12 hours) means missed doses may increase thromboembolism risk 3, 5
• Limited long-term real-world adherence data outside structured anticoagulation clinics 3