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

Abstract

BackgroundDirect-acting oral anticoagulants are first-line agents for prevention of stroke in patients with nonvalvular atrial fibrillation (NVAF), but data are limited for the oldest patients, and with reduced dosing. ObjectivesThe purpose of this study was to determine steady-state apixaban peak and trough concentrations during routine care of older adults with NVAF, compare concentrations to clinical trial concentrations, and explore factors associated with concentrations. MethodsA cross-sectional study of medically stable older adults with NVAF (age ≥75 years or ≥70 years if Black) receiving apixaban. Peak (2.0-4.4 hours post-dose) and trough (before next dose) concentrations were determined by anti-Xa activity calibrated chromogenic assay. Patient characteristics associated with concentrations were determined by multivariate modeling. ResultsThe median age of patients (n = 115) was 80 (interquartile range: 77-84) years. The cohort comprised 46 women and 69 men; of which 98 are White, 11 are Black, and 6 are Asian. With 5 mg twice daily per labelling (n = 88), peak concentrations were higher in women: 248 ± 105 vs 174 ± 67 ng/mL in men (P < 0.001) and exceeded expected 95% range in 6 of 30 vs 0 of 55 men (P = 0.002). With 2.5 mg twice daily per label (n = 11), concentrations were <5 mg twice daily (peak: 136 ± 87 vs 201 ± 90 ng/mL, P = 0.026; trough: 65 ± 28 vs 109 ± 56 ng/mL, P < 0.001), but not different than 2.5 mg twice daily without reduction criteria (n = 13; peak: 132 ± 88 ng/mL; trough: 65 ± 31 ng/mL). Covariates associated with concentrations included sex, number of daily medications, and creatinine clearance. ConclusionsOlder women had higher than expected peak apixaban concentrations, and 2.5 mg twice daily produced lower concentrations than standard dosing. Factors not currently included in dosing recommendations affected concentrations. The impact of apixaban concentrations on outcomes needs evaluation.