Background We evaluated the pharmacokinetics (PK) of low-dose (15 mg) edoxaban in very elderly patients (≥80 years) with nonvalvular atrial fibrillation (NVAF) and high bleeding risk.

Methods This subanalysis of the phase 3, randomized, double-blind, placebo-controlled, multicenter ELDERCARE-AF study evaluated edoxaban plasma concentrations and compared them with the Japanese population of the ENGAGE AF-TIMI 48 and Japanese severe renal impairment (SRI) studies.

Results The PK analysis population included 451 patients, 53.8% of whom concomitantly used antiplatelet drugs, 41.0% had SRI, and 38.0% had low body weight. Edoxaban plasma concentrations at trough and 1 to 3 hours post-dose in ELDERCARE-AF were 17.3 ± 13.9 (n = 427) and 93.3 ± 57.8 ng/mL (n = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 (n = 79; 12.4 ± 12.1 and n = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group (n = 83; 25.1 ± 36.6 and n = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study (n = 39; 18.4 ± 11.2 and n = 40; 96.8 ± 48.3 ng/mL, respectively). ELDERCARE-AF patients with SRI and low body weight (≤45 kg) had higher concentrations than those without, and those taking antiplatelet drugs had lower concentrations than those who were not.

Conclusion PK data support edoxaban 15 mg once daily for very elderly NVAF patients with high bleeding risk, with caution for patients with SRI and/or low body weight.

背景 我们评估了低剂量（15 mg）艾多沙班在患有非瓣膜性心房颤动（NVAF）和高出血风险的高龄患者（≥80 岁）中的药代动力学（PK）。

方法 这项 3 期、随机、双盲、安慰剂对照、多中心 ELDERCARE-AF 研究的亚分析评估了艾多沙班血浆浓度，并将其与 ENGAGE AF-TIMI 48 和日本严重肾功能不全 (SRI) 研究的日本人群进行比较。

结果 PK分析人群包括451例患者，其中53.8%同时使用抗血小板药物，41.0%有SRI，38.0%有低体重。 ELDERCARE-AF 中艾多沙班血浆浓度在谷值和给药后 1 至 3 小时分别为 17.3 ± 13.9 ( n  = 427) 和 93.3 ± 57.8 ng/mL ( n  = 447)。这些值略高于 ENGAGE AF-TIMI 48 中的 15 mg 组（分别为n  = 79；12.4 ± 12.1 和n  = 115；78.7 ± 45.0 ng/mL），低于 ENGAGE AF-TIMI 48 高剂量组减少至 30 mg 组（分别为n  = 83；25.1 ± 36.6 和n  = 111；150 ± 91.6 ng/mL），但与日本 SRI 研究类似（n  = 39；18.4 ± 11.2 和n  = 40；96.8 ±分别为 48.3 纳克/毫升）。患有SRI和低体重（≤45 kg）的ELDERCARE-AF患者浓度高于未服用抗血小板药物的患者，而服用抗血小板药物的患者浓度低于未服用抗血小板药物的患者。

结论 PK 数据支持艾多沙班 15 mg 每天一次用于具有高出血风险的高龄 NVAF 患者，对于 SRI 和/或低体重患者应谨慎使用。