Criteria for Low-Dose Eliquis (Apixaban)
For atrial fibrillation, reduce apixaban from 5 mg twice daily to 2.5 mg twice daily only when at least 2 of the following 3 criteria are present: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL. 1
Dose Reduction Criteria for Atrial Fibrillation
The FDA-approved criteria require at least 2 of 3 characteristics to be present simultaneously 1:
This is consistent across major guidelines including the American Heart Association 3, European Society of Cardiology 3, and European Heart Rhythm Association 3.
Critical Pitfall to Avoid
Do not reduce the dose if only 1 criterion is present. 2 The presence of a single dose-adjustment criterion does not justify dose reduction and may lead to underdosing with increased thromboembolic risk. In the ARISTOTLE trial, patients receiving standard-dose apixaban (5 mg twice daily) with 0 or 1 dose-adjustment criterion had better outcomes than those inappropriately receiving reduced doses 4.
Special Population: End-Stage Renal Disease on Hemodialysis
For patients with end-stage renal disease on stable hemodialysis 3:
- Standard dose: 5 mg twice daily 3
- Reduce to 2.5 mg twice daily only if age ≥80 years OR body weight ≤60 kg (note: only 1 criterion needed in this population, not 2) 3, 2
Recent observational data suggest that standard-dose apixaban (5 mg twice daily) in dialysis patients was associated with significantly lower risks of stroke/systemic embolism and death compared to reduced-dose apixaban (2.5 mg twice daily) 5.
Other Indications for 2.5 mg Twice Daily Dosing
VTE Prophylaxis After Orthopedic Surgery
- All patients receive 2.5 mg twice daily regardless of age, weight, or renal function 1
- Initial dose 12-24 hours post-surgery 1
Extended-Phase VTE Treatment (Secondary Prevention)
- 2.5 mg twice daily after completing at least 6 months of standard anticoagulation for DVT/PE 2, 1
- This reduced dose is used for long-term secondary prevention, not acute treatment 2
Renal Function Considerations
For creatinine clearance >30 mL/min in atrial fibrillation patients, no dose adjustment is needed based on renal function alone unless the patient meets at least 2 of the 3 dose-reduction criteria 3, 2.
Severe renal impairment (CrCl 15-29 mL/min): The dose should be 2.5 mg twice daily if the patient also has CrCl in this range, as this alone may warrant dose reduction in some guidelines 3, though FDA labeling emphasizes the 2-of-3 criteria 1.
Monitoring Requirements
- Evaluate renal function before initiation and at least annually 2
- Use Cockcroft-Gault method for creatinine clearance calculation 3, 2
- Reassess body weight and renal function periodically, as changes may affect dose-reduction criteria status 2
Evidence Supporting Dose-Adjustment Strategy
The ARISTOTLE trial demonstrated that patients with ≥2 dose-adjustment criteria receiving apixaban 2.5 mg twice daily had lower drug concentrations than standard-dose patients, but the effects versus warfarin were consistent for both efficacy (stroke/systemic embolism reduction) and safety (major bleeding reduction) 4. The interaction p-values were non-significant (p=0.26 for stroke, p=0.25 for major bleeding, p=0.72 for death), supporting the appropriateness of dose adjustment in this population 4.
However, in the AUGUSTUS trial of patients with atrial fibrillation and recent acute coronary syndrome or PCI, less than half of patients receiving reduced-dose apixaban actually met dose-reduction criteria, highlighting the problem of inappropriate underdosing in clinical practice 6.