BACKGROUND Apixaban is increasingly used instead of vitamin K antagonists (VKAs) for long-term anticoagulation during HeartMate 3 (HM3) support. However, data on its pharmacokinetics in this context is lacking. We present real-world data on apixaban levels and outcomes in adult and pediatric HM3 patients, and evaluate our dosing strategy based on plasma sampling. METHODS Since June-2023, all new HM3 recipients were initiated on apixaban. Additionally, hospitalized adult HM3 patients were transitioned from VKA to apixaban. Trough apixaban levels were measured in all patients, and dose adjustment was considered to exceed 50ng/ml. RESULTS This retrospective study includes 34 HM3 patients, 4 pediatric (all primary use) and 30 adult patients (16 primary use). In primary use, apixaban was started at median of 14 (interquartile range [IQR]: 11-16, pediatric) and 11 (IQR: 6-13, adult) days postoperatively. No major coagulopathic events occurred during an overall follow-up of 3,191 patient-days. Six minor bleeding events occurred (0.69 events per patient-year), mostly (67%) during dual therapy with aspirin. Fourteen patients had dose adjustment; median trough and peak levels on final dosage were 73 (IQR: 50-92) and 179 (IQR: 133-242) ng/ml in the pediatric group and 109 (IQR: 83-144) and 176 (IQR: 134-228) ng/ml in the adult cohort, respectively. Inter- and intraindividual variation in apixaban peak levels was considerable, while trough levels showed less variability. CONCLUSIONS With a dosing strategy to target trough apixaban levels of >50ng/ml, there were no thrombotic events during a follow-up of 3,191 patient-days (of which 820 patient-days in children). We observed no major, and only few non-major bleeds, mainly in patients concomitantly taking aspirin.

中文翻译：

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支持 HeartMate 3 的患者的阿哌沙班血浆水平。


背景在 HeartMate 3 （HM3） 支持期间，阿哌沙班越来越多地用于代替维生素 K 拮抗剂 （VKA） 进行长期抗凝。然而，在这种情况下缺乏关于其药代动力学的数据。我们提供了成人和儿童 HM3 患者阿哌沙班水平和结果的真实世界数据，并根据血浆采样评估我们的给药策略。方法 自 2023 年 6 月以来，所有新的 HM3 受体均开始使用阿哌沙班。此外，住院的成年 HM3 患者从 VKA 过渡到阿哌沙班。测量所有患者的谷阿哌沙班水平，剂量调整被认为超过 50ng/ml。结果 这项回顾性研究包括 34 名 HM3 患者、4 名儿科患者 （所有主要使用） 和 30 名成人患者 （16 名主要使用）。在初次使用中，阿哌沙班在术后 14 天 （四分位距 [IQR]： 11-16，儿童） 和 11 天 （IQR： 6-13，成人） 开始。在 3,191 个患者日的整体随访中未发生重大凝血病事件。发生 6 例轻微出血事件 （每患者年 0.69 次事件），大部分 （67%） 发生在阿司匹林二联治疗期间。14 例患者进行了剂量调整;儿童组最终剂量的中位谷值和峰值水平分别为 73 （IQR： 50-92） 和 179 （IQR： 133-242） ng/ml，成人队列分别为 109 （IQR： 83-144） 和 176 （IQR： 134-228） ng/ml。阿哌沙班峰值水平的个际和个体内差异相当大，而谷水平的变异性较小。结论 对于针对 >50ng/ml 的阿哌沙班谷水平的给药策略，在 3,191 个患者天 （其中儿童 820 个患者日） 的随访期间没有血栓事件。我们没有观察到严重出血，只有少数非严重出血，主要发生在同时服用阿司匹林的患者中。