Apixaban Non-Inferiority to Enoxaparin
Apixaban is non-inferior to enoxaparin for treatment of acute venous thromboembolism (VTE), but the answer varies significantly by clinical indication—apixaban demonstrates superiority for post-knee arthroplasty prophylaxis, non-inferiority for VTE treatment, but inferiority for medical thromboprophylaxis in acutely ill patients.
VTE Treatment (DVT/PE)
For treatment of acute DVT and PE, apixaban is non-inferior to enoxaparin/warfarin combination therapy with superior safety. 1, 2
AMPLIFY Trial Evidence
- In the AMPLIFY trial, apixaban (10 mg twice daily for 7 days, then 5 mg twice daily for 6 months) was non-inferior to enoxaparin/warfarin for preventing recurrent VTE or VTE-related death (2.3% vs 2.7%; relative risk 0.84,95% CI 0.60-1.18) 1, 2
- Apixaban demonstrated significantly superior bleeding outcomes with major bleeding at 0.6% versus 1.8% for enoxaparin/warfarin (relative risk 0.31,95% CI 0.17-0.55; P<0.001) 1
- Apixaban also reduced all-cause hospitalizations (5.72% vs 7.07%; hazard ratio 0.804,95% CI 0.650-0.995, P=0.045) and shortened hospital length of stay (0.57 vs 1.01 days, P<0.0001) 3
Guideline Recommendations
- The American College of Chest Physicians recommends apixaban over enoxaparin for acute DVT treatment in non-cancer patients due to comparable efficacy and significantly lower bleeding risk 4
- For cancer patients with VTE, LMWH (enoxaparin) remains preferred over apixaban (Grade 2C recommendation) 4
Post-Surgical Thromboprophylaxis
Knee Arthroplasty
Apixaban is superior to enoxaparin for VTE prophylaxis after total knee replacement. 5
- In ADVANCE-2, apixaban 2.5 mg twice daily (starting 12-24 hours post-surgery) was superior to enoxaparin 40 mg once daily for preventing total VTE or all-cause mortality (15.06% vs 24.37%; relative risk 0.62,95% CI 0.51-0.74; P<0.0001) 1, 5
- Major or clinically relevant non-major bleeding was similar between groups (4% vs 5%, P=0.09) 5
Hip Arthroplasty
- In ADVANCE-3, apixaban was superior to enoxaparin 40 mg once daily for hip replacement (1.4% vs 3.9%; relative risk 0.36,95% CI 0.22-0.54; P<0.001) 1
Important Caveat
- In ADVANCE-1 (comparing apixaban to enoxaparin 30 mg twice daily in knee arthroplasty), apixaban did not meet prespecified statistical criteria for non-inferiority, though bleeding was significantly lower with apixaban 1
Medical Thromboprophylaxis
Apixaban is NOT superior to enoxaparin for thromboprophylaxis in acutely ill medical patients and carries increased bleeding risk. 1
ADOPT Trial Evidence
- Apixaban 2.5 mg twice daily for 30 days was not superior to enoxaparin 40 mg once daily for 6-14 days in preventing VTE in acutely ill medical patients (2.71% vs 3.06%; relative risk 0.87,95% CI 0.62-1.23) 1
- Major bleeding was significantly higher with apixaban (0.47% vs 0.19%; relative risk 2.58,95% CI 1.02-7.24; P<0.04) 1
- Extended thromboprophylaxis with apixaban was not superior to shorter enoxaparin courses and caused more bleeding 1
Renal Impairment Considerations
Apixaban has advantages over enoxaparin in moderate renal impairment but should be avoided in severe renal dysfunction. 1, 6
- Apixaban has only 27% renal elimination compared to enoxaparin's predominantly renal clearance 1, 7
- Avoid apixaban when CrCl <15 mL/min (patients with CrCl <25 mL/min were excluded from clinical trials) 1, 8, 6
- Enoxaparin requires dose adjustment when CrCl <30 mL/min, making apixaban potentially preferable in moderate renal impairment (CrCl 25-50 mL/min) 1
Clinical Decision Algorithm
Use apixaban over enoxaparin when:
- Treating acute VTE in non-cancer patients (non-inferior efficacy, superior bleeding profile) 1, 4, 2
- Post-knee or hip arthroplasty prophylaxis (superior efficacy, similar bleeding) 1, 5
- Moderate renal impairment (CrCl 25-50 mL/min) where enoxaparin dosing is problematic 1
- Patient preference for oral administration over subcutaneous injections 7
Use enoxaparin over apixaban when: