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How to handle the delayed or the missed dose of edoxaban in patients with non-valvular atrial fibrillation: model-informed remedial strategy
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  • Yi-wei Yin,
  • Xiaoqin Liu,
  • Jiaqin Gu,
  • Ziran Li,
  • Zheng Jiao
Yi-wei Yin
Shanghai Jiao Tong University Affiliated Chest Hospital

Corresponding Author:yinyiweivv@gmail.com

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Xiaoqin Liu
Huashan Hospital Fudan University
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Jiaqin Gu
Shanghai Jiao Tong University Affiliated Chest Hospital
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Ziran Li
Huashan Hospital Fudan University
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Zheng Jiao
Shanghai Jiao Tong University Affiliated Chest Hospital
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Aim: Edoxaban is a non-vitamin K antagonist oral anticoagulant (NOAC) widely used for long-term stroke prevention in patients with non-valvular atrial fibrillation (NVAF). Adherence to NOACs is unsatisfactory and decreases over time. The aim of this study was to explore appropriated remedial dosing regimens for non-adherent edoxaban-treated NVAF patients through the Monte Carlo simulation. Methods: Six proposed regimens were compared with the recommendations in the European Heart Rhythm Association (EHRA) guide regarding the trough total deviation time considering both edoxaban plasma concentration and inactive factor Xa activity. Monte Carlo simulations were performed using RxODE based on the published population pharmacokinetics/pharmacodynamics model. Results: The proposed remedial strategies were different from EHRA recommendations and were related to delay duration. The missed dose can be taken immediately if the delay time is within 11 h. When the delay period is between 12 and 19 h, a half dose followed by a regular dosing schedule is recommended. When the delay time exceeds 19 h, a full dose followed by a half dose is preferred compared to that recommended in the EHRA guide. Our proposed strategies resulted in a shorter total deviation time than EHRA guide. Conclusion: PK/PD modelling and simulation are effective in developing and evaluating the remedial strategies of edoxaban, which could help maximize its therapeutic effect.
31 Oct 2021Submitted to British Journal of Clinical Pharmacology
15 Nov 2021Submission Checks Completed
15 Nov 2021Assigned to Editor
26 Nov 2021Reviewer(s) Assigned
15 Dec 2021Review(s) Completed, Editorial Evaluation Pending
22 Jan 2022Editorial Decision: Revise Major
07 Mar 20221st Revision Received
08 Mar 2022Submission Checks Completed
08 Mar 2022Assigned to Editor
08 Mar 2022Review(s) Completed, Editorial Evaluation Pending
14 Mar 2022Editorial Decision: Accept
06 Apr 2022Published in British Journal of Clinical Pharmacology. 10.1111/bcp.15316