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Responses of prothrombin time and activated partial thromboplastin time to edoxaban in Japanese patients with non-valvular atrial fibrillation: characteristics of representative reagents in Japan (CVI ARO 7)

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Abstract

The aims of this study were to determine the distribution of plasma concentration of edoxaban (PC-Ed) with their 90% interval (on therapy range) and its correlation with anticoagulation markers in patients with non-valvular atrial fibrillation (NVAF). Consecutive 97 NVAF patients under edoxaban therapy were evaluated (60/30 mg dose, n = 48/49; men/women, n = 71/26; age, 69 years). CHADS2 score 0, 1, and ≥ 2 were 27%, 44%, and 29%, respectively. The mean (90% interval) of PC-Ed by LC–MS/MS was 194.3 (49.4–345.3) and 17.0 (4.8–40.7) ng/mL at peak (2–4 h post-dose) and trough (pre-dose), respectively. Correlation of prothrombin time (PT) with PC-Ed was higher than that of activated partial thromboplastin time (aPTT). Among 6 PT reagents, Coagupia PT–N and Simplastin Excel S (both PT reagents) showed the highest predictive capability for the upper outlier of PC-Ed at peak and trough. Among 4 aPTT reagents, only Thrombocheck APTT measured at peak had a significant predictive capability. When using PT reagents, both peak and trough sampling showed a similar predictive capability for the upper outliers of PC-Ed with a high sensitivity, but a relatively low specificity. We demonstrated the distributions of plasma concentration, PT with 6 reagents, and aPTT with 4 reagents under edoxaban therapy in Japanese patients with NVAF, showing their 90% intervals. For predicting the upper outlier of PC-Ed, PT was more sensitive compared with aPTT, whereas predicting capability for the outliers of PC-Ed was mostly similar between peak and trough samplings among PT reagents (UMIN 000032492).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, The Cardiovascular Institute, 3-2-19 Nishi-azabu, Minato-ku, Tokyo, 106-0031, Japan

    Shinya Suzuki, Naoharu Yagi, Takayuki Otsuka, Takuto Arita & Takeshi Yamashita

  2. Medical Science Department, Daiichi Sankyo Co., Ltd, Tokyo, Japan

    Yoshiyuki Morishima

  3. Safety and Risk Management Department, Daiichi Sankyo Co., Ltd, Tokyo, Japan

    Atsushi Takita

Authors
  1. Shinya Suzuki
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  2. Yoshiyuki Morishima
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  4. Naoharu Yagi
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  7. Takeshi Yamashita
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Correspondence to Shinya Suzuki.

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Conflict of interest

This work was financially supported by Daiichi Sankyo. Dr. Suzuki received research funding from Daiichi Sankyo and Mitsubishi-Tanabe. Dr. Yamashita received research funding from Boehringer Ingelheim and Daiichi Sankyo, and remuneration from Boehringer Ingelheim, Daiichi Sankyo, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Eisai and Ono Pharmaceutical. Dr. Morishima and Mr. Takita are employees of Daiichi Sankyo. The management of this work was supported by Cardiovascular Institute Academic Research Organization (CVI ARO) [25,26,27,28,29,30,31,32,33,34].

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Suzuki, S., Morishima, Y., Takita, A. et al. Responses of prothrombin time and activated partial thromboplastin time to edoxaban in Japanese patients with non-valvular atrial fibrillation: characteristics of representative reagents in Japan (CVI ARO 7). Heart Vessels 34, 2011–2020 (2019). https://doi.org/10.1007/s00380-019-01438-6

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