Edoxaban monitoring strategy using chromogenic anti-Xa assays among patients with atrial fibrillation

Abstract Introduction Edoxaban, a direct oral anticoagulant for atrial fibrillation (AF) patients, reduces stroke and systemic embolism risk. However, dosing is complicated by factors such as renal function, body weight, and concomitant medications, which can significantly impact plasma concentration. ESC guidelines recommend chromogenic anti-Xa assays in complex cases. Purpose This study aimed to measure the edoxaban concentrations twice at one- or two-month intervals among stable ambulatory patients with AF to evaluate the monitoring strategy of reduced dose anticoagulant therapy. Methods This longitudinal study was conducted from February to November 2024. Inclusion criteria: AF patients on a stable 30 mg daily dose of edoxaban for at least 7 days. Exclusion criteria: (1) at least one missed dose in the last seven days; (2) creatinine clearance <30 mL/min (Cockcroft-Gault formula); (3) serious comorbidities that could affect prognosis; (4) taking amiodarone (or used 2 months ago), digoxin (or used 2 weeks ago), dronedarone, verapamil, and other known drugs/substances significantly impacting edoxaban concentrations or anti-Xa assays; (5) initiation or discontinuation of another daily medication or supplement within the past week, or within five half-lives for medications taken weekly or less frequently. Blood samples were collected at trough concentration immediately prior to the next scheduled dose and at peak concentration 1.5 hours (± 10 minutes) post-dose administration. Functional anti-Xa assays Hyphen Biomed was used. Nonparametric descriptive statistics, such as median [Q1–Q3], were utilised in Jamovi. Results Eight patients participated in this study. The median Ctrough and Cmax were 20 [15.5-24.3] and 190 [158.5-218.5] ng/mL at the first visit, and 19 [17.5-21.5] and 183 [141.0-206.0] ng/mL at the second visit, respectively. The median of absolute deviations from the first visit was 28.8% [9.0%-31.9%]. More detailed data are presented in the graph. No adverse effects were observed. Conclusions Substantial variation of edoxaban concentrations were observed in repeated measurements among users of 30 mg dose. Larger and dedicated studies are needed to investigate confounding factors and optimal monitoring methods of edoxaban concentrations in such high-risk individuals.