Influence of age on the relationship between apixaban concentration and anti-factor Xa activity in older patients with non-valvular atrial fibrillation

Background/objectivesDespite lower major bleeding rates associated with direct oral anticoagulants (DOACs) as compared to conventional warfarin therapy, bleeding rates remain higher in older patients compared to younger patients suggesting a potential role for DOAC measurements. The objective of this study is to examine the effect of age on the relationship between apixaban concentrations and anti-Factor Xa activity in patients with non-valvular atrial fibrillation (NVAF).MethodsThis is a retrospective analysis based on a database created using data from the ARISTOTLE study. Outpatient, stable adult patients with NVAF receiving apixaban were included in this study. Data collection consisted of apixaban concentration, anti-Factor Xa activity, age, weight, creatinine, and co-medications.ResultsThe database composed of 2058 patients receiving apixaban. Distribution of race, NVAF subtype, and aspirin use was fairly similar across each age quantile. Older patients received a higher number of co-medications and received the 2.5 mg apixaban dose more often as compared to younger patients (22% vs. < 1%). Linear regression demonstrated that the unadjusted slope for apixaban concentration effect on anti-Factor Xa activity was similar across each age quantile. Although, the overall adjusted linear regression analysis demonstrated that the age by concentration interaction was statistically significant, relative differences in anti-Factor Xa activity (< 8%) were not clinically meaningful.ConclusionData on apixaban concentrations and anti-Factor Xa activity from a pivotal randomized double-blind study of apixaban for the prevention of stroke in NVAF patients have confirmed that the chromogenic anti-Factor Xa activity assay can accurately assess apixaban concentrations in patients regardless of age. Age was not associated with a clinically relevant change in the apixaban vs. anti-Factor Xa activity response relationship and target ranges are unchanged