Are there guidelines to decrease apixaban (Eliquis) dose in elderly patients with high bleeding risk from falls?

Guidelines for Apixaban (Eliquis) Dose Adjustment in Elderly Patients with High Fall Risk

According to current guidelines, fall risk alone should not be a reason to reduce the dose of apixaban (Eliquis) in elderly patients, as the benefits of stroke prevention typically outweigh the bleeding risks even in patients at high risk of falls. 1

Understanding Fall Risk and Anticoagulation

• Fall risk is commonly cited as a reason for underdosing apixaban, but this practice is not supported by evidence-based guidelines 1
• A Markov decision analysis demonstrated that an elderly patient would need to fall 458 times per year for the risks of apixaban to outweigh its benefits compared to aspirin 2
• The European Heart Rhythm Association (EHRA) guidelines specifically state that anticoagulation should only be withheld from patients with severe uncontrolled falls (e.g., epilepsy or advanced multisystem atrophy with backwards falls) 1

Appropriate Dose Reduction Criteria for Apixaban

According to the FDA label, apixaban dose should be reduced to 2.5 mg twice daily ONLY when patients meet at least TWO of the following criteria 3:

• Age ≥80 years
• Body weight ≤60 kg
• Serum creatinine ≥1.5 mg/dL

Common Reasons for Inappropriate Underdosing

Studies have identified several factors that lead to inappropriate underdosing of apixaban in elderly patients 1:

• Fall risk/frailty/dementia 1
• History of bleeding or active bleeding 1
• Concurrent use of antiplatelet medications 1
• Advanced age (as a single factor) 1
• Decreased renal function (as a single factor) 1
• Low body weight (as a single factor) 1

Clinical Consequences of Inappropriate Dosing

• Underdosing apixaban is the most common form of inappropriate prescribing (9.4%-40.4% of apixaban prescriptions) 1
• Counterintuitively, some studies have found higher bleeding rates in underdosed patients, likely because these patients had higher baseline bleeding risk 1
• A recent study found no significant differences in stroke (2.7% vs 2.2%) or bleeding outcomes between patients receiving off-label reduced dosing versus standard dosing 4
• However, all-cause mortality was higher in the off-label reduced-dose group (10.9% vs 1.4%) 4

Recommendations for High Fall Risk Elderly Patients

1. Do not reduce apixaban dose based on fall risk alone 1
2. Assess for the FDA-approved dose reduction criteria (≥2 of: age ≥80 years, weight ≤60 kg, creatinine ≥1.5 mg/dL) 3
3. Consider the following factors that may genuinely increase bleeding risk 1:
   • History of bleeding or predisposition for bleeding (anemia, thrombocytopenia)
   • Concomitant use of antiplatelet drugs, NSAIDs, or systemic corticosteroids
   • Severe frailty

Special Considerations

• For patients with severe uncontrolled falls, consider alternatives to anticoagulation or specialist consultation 1
• In patients with dementia, ensure medication adherence through caregiver support 1
• Regular monitoring of renal function is essential as elderly patients may experience fluctuations 1
• The benefit of NOACs over vitamin K antagonists has been best demonstrated for edoxaban and apixaban in frail elderly patients 1

Conclusion

The evidence strongly suggests that fall risk alone should not lead to dose reduction of apixaban in elderly patients. The benefits of stroke prevention with appropriate dosing typically outweigh the bleeding risks, even in patients at high risk for falls. Clinicians should follow the FDA-approved dose reduction criteria and avoid inappropriate underdosing based solely on concerns about falls.