Purpose

To investigate the distribution of plasma apixaban levels and their relationships with clinical outcomes in elderly patients with atrial fibrillation (AF).

Method

The J-ELD AF Registry is a multicenter prospective observational study of Japanese non-valvular AF patients aged ≥75 years taking an on-label dose of apixaban (3015 patients from 110 institutions). Among them, plasma apixaban levels at trough were estimated by anti-Xa assay (Api-AXA) in 943 patients. Patients with standard (5 mg bid; n = 431) and reduced (2.5 mg bid; n = 512) dose were further divided into two groups with low and high Api-AXA levels (boundary: median value).

Results

The incidence rates (per 100 person-years) of events in the low- and high-Api-AXA groups were as follows: 1.48 and 1.99 (log-rank test, P = 0.695) for stroke or systemic embolism, 0.98 and 1.49 (P = 0.652) for bleeding requiring hospitalization, and 0.49 and 0.99 (P = 0.565) for total deaths in patients with standard dose, versus 0.84 and 1.68 (P = 0.414), 0.42 and 4.64 (P = 0.004), and 2.52 and 6.65 (P = 0.035) in patients with a reduced dose, respectively. In multivariate Cox regression analysis among patients with a reduced dose, a high Api-AXA level was independently associated with bleeding requiring hospitalization (HR 12.12, 95% CI: 1.56–94.22) and nonsignificantly with total deaths.

Conclusions

A high trough apixaban level in patients indicated for standard dose was not associated with adverse events, while a high apixaban level in patients indicated for a reduced dose was associated with bleeding requiring hospitalization.

中文翻译：

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老年房颤患者阿哌沙班水平评估的临床意义：J-ELD AF登记亚组分析。

目的

研究血浆阿哌沙班水平的分布及其与老年房颤（AF）患者临床预后的关系。

方法

J-ELD AF注册中心是一项多中心前瞻性观察性研究，研究对象是≥75岁的日本非瓣膜性AF患者，他们服用了阿哌沙班的标签剂量（来自110个机构的3015例患者）。其中，通过抗Xa分析（Api-AXA）对943例患者的血浆阿哌沙班水平进行了估算。标准剂量（5 mg bid；n  = 431）和减少 剂量（2.5 mg bid；n = 512）的患者被进一步分为两组，Api-AXA水平低和高（边界：中值）。

结果

低和高Api-AXA组的事件发生率（每100人年）如下： 中风或全身性栓塞的1.48和1.99（对数秩检验，P = 0.695），0.98和1.49（ 对于需要住院的出血，P = 0.652） ，标准剂量患者的总死亡为0.49和0.99（P = 0.565），而0.84和1.68（P  = 0.414），0.42和4.64（P  = 0.004），2.52和6.65 （P = 0.035）。在减少剂量的患者中进行多因素Cox回归分析，高Api-AXA水平与需要住院的出血无关（HR 12.12，95％CI：1.56-94.22），与总死亡无关紧要。

结论

指示标准剂量的患者高谷阿哌沙班水平与不良事件无关，而指示剂量减少的患者高阿哌沙班水平与需要住院的出血有关。