Apixaban Concentrations in Routine Clinical Care of Older Adults With Nonvalvular Atrial Fibrillation

Area of Science:

• Pharmacology
• Geriatrics
• Cardiology

Background:

• Direct-acting oral anticoagulants (DOACs) are standard for stroke prevention in nonvalvular atrial fibrillation (NVAF).
• Limited data exist on DOACs, specifically apixaban, in the oldest patient populations and with reduced dosing regimens.

Purpose of the Study:

• To assess steady-state apixaban peak and trough concentrations in elderly NVAF patients under routine care.
• To compare these concentrations with those from clinical trials.
• To identify patient-specific factors associated with apixaban concentrations.

Main Methods:

• Cross-sectional study of medically stable NVAF patients aged 75 years or older (or 70+ if Black).
• Measured apixaban peak (2-4.4h post-dose) and trough (pre-dose) concentrations using anti-Xa activity assay.
• Multivariate modeling was employed to determine factors associated with observed concentrations.

Main Results:

• Older women (n=46) exhibited higher peak apixaban concentrations (248 ± 105 ng/mL) compared to men (n=69) (174 ± 67 ng/mL) on standard 5mg twice daily dosing (P < 0.001).
• Reduced 2.5mg twice daily dosing resulted in significantly lower peak (136 ± 87 ng/mL) and trough (65 ± 28 ng/mL) concentrations compared to standard dosing.
• Concentrations were influenced by patient sex, daily medication count, and creatinine clearance.

Conclusions:

• Elderly women may experience higher-than-expected apixaban peak concentrations.
• Reduced apixaban dosing (2.5mg BID) leads to lower concentrations than standard dosing.
• Additional factors beyond current dosing guidelines impact apixaban concentrations in older adults, warranting further outcome-based evaluation.