Clinical implications of assessment of apixaban levels in elderly atrial fibrillation patients: J-ELD AF Registry sub-cohort analysis

Abstract

Abstract Background Randomized clinical trials demonstrated the efficacy and safety of apixaban in preventing stroke in patients with atrial fibrillation (AF). However, data on distribution of apixaban levels and their relationships with clinical outcomes are limited. Purpose To evaluate the distribution of blood apixaban concentration and its relationship with clinical outcomes. Method The J-ELD AF Registry is a large-scale, multicenter prospective observational study of Japanese non-valvular AF patients aged ≥75 years taking on-label dose (standard dose of 5 mg bid or reduced dose of 2.5 mg bid) of apixaban. Among the entire cohort (3,015 patients from 110 institutions), plasma apixaban levels at trough was measured by anti-Xa assay (Api-AXA) in 943 patients. The 943 patients were divided into 2 groups by the apixaban dose (standard dose [n=431] and reduced dose [n=512]) and each group was further divided into 2 groups with low and high Api-AXA levels compared with the median value. Results In patients with standard dose, the incidence rates (/100 person-years) of stroke or systemic embolism (1.48 and 1.99), bleeding requiring hospitalization (0.98 and 1.49), and total deaths (0.49 and 0.99) were comparable between low and high Api-AXA groups, respectively. In patients with reduced dose, although the incidence rates (/100 person-years) of stroke or systemic embolism (0.84 and 1.68) were comparable, bleeding requiring hospitalization (0.42 and 4.64), and total deaths (2.52 and 6.65) were significantly higher in high Api-AXA group than in low Api-AXA group. Multivariable Cox regression analysis revealed that in patients with reduced dose, high Api-AXA level was independently associated with bleeding requiring hospitalization (HR 12.12, 95% CI: 1.56–94.22, P=0.017) and insignificantly with total deaths (HR 2.15, 95% CI: 0.83–5.55, P=0.116). Conclusions High trough apixaban level in patients with standard dose was not associated with adverse events, while that in patients with reduced dose was associated with bleeding requiring hospitalization and total deaths. Measurement of apixaban levels may be informative in elderly patients indicated for reduced dose possibly with the intent of risk stratification and decision making. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Bristol-Myers Squibb K.K.