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Aim: As the direct oral anticoagulant most recently approved in China, data pertaining to clinical edoxaban use are still scarce. This study investigated the prevalence of and contemporary trends in edoxaban prescription among Chinese patients as well as factors associated with its inappropriate use in a multicentre registry of patients treated in real‐world clinical practice. Methods: This real‐world, prospective, multicentre and non‐interventional study included 1005 inpatients treated with edoxaban. According to National Medical Products Administration and European Heart Rhythm Association guidelines, edoxaban therapy was determined to be appropriate or inappropriate in each case. Results: The median patient age was 70.0 years (interquartile range 61.0‐78.0 years) and 46.3% were women. Overall, 456 (45.4%) patients received inappropriate edoxaban therapy, and common issues included an inappropriately low dosage (183, 18.2%) or wrong drug selection (109, 10.8%), high dosage (73, 7.3%), unreasonable off‐label use (49, 4.9%), contraindicated medication combinations (27, 2.7%) and incorrect administration timing (16, 1.6%). Several factors, such as age ≥75 years (odds ratio [OR] = 1.921, 95% confidence interval [CI] 1.355‐2.723, P < 0.001), weight >60 kg (OR = 2.657, 95%CI 1.970‐3.583, P < 0.001), severe renal insufficiency (OR = 1.988, 95% CI 1.043‐3.790, P = 0.037), current anaemia (OR = 1.556, 95% CI 1.151‐2.102, P = 0.004) and history of bleeding (OR = 2.931, 95% CI 1.605‐5.351, P < 0.001) were associated with an increased risk of inappropriate edoxaban therapy, whereas factors associated with cardiovascular specialties, such as admission to a cardiovascular department (OR = 0.637, 95% CI 0.464‐0.873, P = 0.005), dronedarone use (OR = 0.065, 95% CI 0.026‐0.165, P < 0.001) and amiodarone use (OR = 0.365, 95% CI 0.209‐0.637, P < 0.001) decreased this risk. Conclusion: In this real‐world study, 45.4% of patients received an inappropriate treatment with edoxaban. Multiple clinical characteristics can help identify patients who should receive edoxaban. Further development and implantation of educational activities and management strategies are needed to ensure the correct use of edoxaban. [ABSTRACT FROM AUTHOR]

The aim was to investigate the bioequivalence of 2 orally administered edoxaban 60-mg tablets and the food effects on the pharmacokinetics of edoxaban. Sixty-four healthy Chinese subjects participated in this open-label, randomized, 2-sequence, 4-period, crossover study. All subjects randomly received 60-mg generic (test) or branded (reference) edoxaban tablet in each period. Plasma edoxaban concentrations were determined using liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters maximum concentration (C max ) and area under the concentration-time curve (AUC) were compared to assess bioequivalence. The geometric least-squares mean ratios for C max , AUC from time 0 to the last measurable time point (AUC 0-t ), and AUC from time 0 extrapolated to infinity (AUC 0-∞ ) were 97.0%, 95.4%, and 96.1%, respectively, in the fasting test, and 98.6%, 100.0%, and 99.8%, respectively, in the fed test. Food increased exposure and prolonged the time to maximum concentration of edoxaban. Both formulations displayed comparable safety profiles, with no serious adverse events reported. The 2 products of edoxaban tablets are bioequivalent and safe in healthy Chinese volunteers. Food may have a modest effect on the pharmacokinetic properties of edoxaban., (© 2022, The American College of Clinical Pharmacology.)

• Edoxaban use is associated with lower risks of new onset hip fractures, medically attended falls and mortality risks compared to warfarin. • This relationship was observed after propensity score matching adjusting for significant confounders. The three direct oral anticoagulants (DOAC), rivaroxaban, apixaban and dabigatran have been associated with lower risks of fractures compared to warfarin. However, no large scale studies have explored the associations with the newest DOAC, edoxaban, with fracture risk. The present study aims to elucidate the effects of edoxaban on the risk of hip fracture amongst elderly patients by comparing the incidence of new onset hip fracture between edoxaban and warfarin users in a Chinese population. This was a retrospective population-based cohort study of patients with edoxaban or warfarin use between January 1st, 2016 and December 31st, 2019 in Hong Kong, China. Patients with less than one-month exposure, medication switching between warfarin and edoxaban, those who died within 30 days after drug exposure, prior human immunodeficiency virus infection, age <50 years old, and those with prior hip fractures were excluded. Propensity score matching (1:2) between edoxaban and warfarin users using the nearest neighbour method was performed based on demographics, prior comorbidities, and use of different medications. The study outcomes were new onset hip fractures, medically attended falls and all-cause mortality. A total of 5014 patients including 579 edoxaban users and 4435 warfarin users (median age: 70 years old [interquartile range (IQR): 62–79], 56.66% males) with a median follow-up of 637.5 (IQR: 320–1073) days were included. In the matched cohort, edoxaban users had significantly lower rates of new onset hip fractures, medically attended falls and all-cause mortality. The protective value of edoxaban use against new onset hip fracture (hazard ratio [HR]: 0.13, 95% confidence interval [CI]: [0.03–0.54], p = 0.0051), medically attended falls (HR: 0.47, [0.29–0.75], p = 0.0018) and all-cause mortality (HR: 0.61, [0.42–0.87], p = 0.0059) in comparison to warfarin use persisted after matching. The significant relationship between edoxaban use and lower fracture risk was preserved in all sensitivity analyses using different approaches using the propensity score. Edoxaban use is associated with lower risks of new onset hip fractures, medically attended falls and mortality risks compared to warfarin after propensity score matching. [ABSTRACT FROM AUTHOR]

1. This study investigated the pharmacokinetics and pharmacodynamics of single-dose edoxaban in healthy Chinese subjects. 2. This single-centre, open-label, 3-occasion, cross-over study enrolled six males and six females. Subjects received a single-oral-dose of edoxaban 30-90 mg in each study occasion under fasting condition. Serial blood samples were collected to measure the plasma concentrations of edoxaban and its major active metabolite D21-2393. Meanwhile, PT, INR, aPTT were measured pre- and post-dose. Safety was assessed. 3. After administration, edoxaban was rapidly absorbed (median T max  =   1-2 h). With rapid transformation, peak concentration of D21-2393 was reached within 2-h post-dose. The elimination half-life of edoxaban was 5-20 h. The dose-exposure relationships were slightly lower-than-dose-proportional for both edoxaban and D21-2393. Although women had higher plasma exposure of edoxaban and D21-2393 than men, it was considered clinically insignificant. 4. The effects of edoxaban on all pharmacodynamic biomarkers were concentration-dependent and linearly-correlated to plasma level of the compound. Minor bleeding was the most commonly reported adverse events. 5. Single oral doses of edoxaban 30-90 mg were safe and well tolerated in healthy Chinese volunteers. 6. The pharmacokinetic and pharmacodynamic profiles of edoxaban in Chinese subjects were comparable to those observed in Caucasian and Japanese populations.