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Target Drug-Calibrated Anti-Xa Activity Assays and Expected Peak–Trough Levels in an Asian Population: A Multicenter Study

  • Original Research Article
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Abstract

Background

For patients taking factor Xa (FXa) inhibitors who have life-threatening bleeding, emergency surgery, drug interactions, etc., a rapid and precise assay is needed to monitor for potential medication failure, to assess safety during periprocedural anticoagulation management, and to manage the care of chronically anticoagulated patients. Anti-factor Xa (anti-Xa) activity assays have been recommended in guidelines, but the evaluation of different calibrations of anti-Xa activity assays and the data on the recommended range are still limited, especially in the Asian population.

Methods

This is a nationwide multicenter methodology exploratory study in an Asian population, including nine hospitals from Beijing, Shanghai, Liaoning, Shandong, Jiangsu, Anhui, Henan, Chongqing, and Fujian. A total of 485 healthy volunteers and 219 patients taking rivaroxaban or apixaban (single dose) were enrolled in the study. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) was employed to detect plasma rivaroxaban and apixaban. The prothrombin time (PT), activated partial thromboplastin time (APTT), and levels of anti-Xa activity were tested as pharmacodynamic parameters in plasma samples. We evaluated the correlation of anti-Xa activity and blood concentration via HPLC-MS, and then compared the two methods of target drug-calibrated and low-molecular-weight heparin (LMWH)-antithrombin–calibrated anti-Xa activity. Correlations between variables were examined using Pearson’s correlation analysis. Logistic regression was applied to evaluate significant differences in anti-Xa activity and blood concentration, using models adjusted by baseline characteristics.

Results

The results suggested anti-Xa activity had better correlation with blood concentrations of apixaban and rivaroxaban than APTT and PT (p < 0.001). Target drug-calibrated anti-Xa activity had better correlation with HPLC-MS results at every dose level and blood collection time (p < 0.001). The expected concentrations (ng/mL) derived from rivaroxaban-calibrated assays of rivaroxaban 10 mg, 15 mg, and 20 mg were about 210, 330, and 270 at peak concentrations, and 28, 44, and 58, respectively, at the trough concentrations.

Conclusions

In this study, we confirm that target drug calibration of anti-Xa activity is a better quantitative detection method for oral direct FXa inhibitors than LMWH-calibrated anti-Xa activity in clinical practice, and expected peak–trough levels are recommended for the Asian population.

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Authors and Affiliations

  1. Department of Pharmacy, Peking University First Hospital, No. 6, Dahongluochang Street, Xicheng District, Beijing, 100034, China

    Zhiyan Liu, Qiufen Xie, Hanxu Zhang, Guangyan Mu, Shuang Zhou, Zining Wang, Qian Xiang & Yimin Cui

  2. School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing, China

    Hanxu Zhang & Yimin Cui

  3. Department of Cardiology, Peking University First Hospital, Beijing, China

    Jie Jiang

  4. Institute of Clinical Pharmacology, Peking University, Beijing, China

    Yimin Cui

Authors
  1. Zhiyan Liu
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  2. Qiufen Xie
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  3. Hanxu Zhang
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  4. Guangyan Mu
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  5. Shuang Zhou
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  6. Zining Wang
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  7. Jie Jiang
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  8. Qian Xiang
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  9. Yimin Cui
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Corresponding authors

Correspondence to Qian Xiang or Yimin Cui.

Ethics declarations

Funding

This study was supported by grants from the National Science and Technology Major Projects for “Major New Drugs Innovation and Development” of China (No. 2018ZX09201014, No. 2017ZX09101001 and No. 2017ZX09304028), National Natural Science Foundation of China (No. 81872940 and No. 81973395), and Natural Science Foundation of Beijing Municipality (No. 7171012).

Conflict of interest

We declare no competing interests.

Ethics approval and consent to participate

The protocol was approved by an independent ethics committee and the Institutional Review Board of Peking University First Hospital and all participating research sub-central hospitals. The trial registration number is NCT03161496. All subjects were enrolled in this study after signing informed consent.

Consent for publication

The manuscript has been approved by all authors for publication. The work described is original research that has not been published previously; nor is it under consideration for publication elsewhere, in whole or in part.

Availability of data and material

All data related to the study have been shown in the article, and other relevant data can be requested from the authors.

Code availability

Not applicable.

Author contributions

(1) Conception and design: YC, QX, and JJ; (2) provision of study materials or patients: ZL, QX, QX, HZ, GM, and SZ; (3) collection and assembly of data: ZL, QX, QX, HZ, GM, and SZ; (4) data analysis and interpretation: ZL, QX, HZ, and QX; (5) manuscript writing and final approval of manuscript: all authors.

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Liu, Z., Xie, Q., Zhang, H. et al. Target Drug-Calibrated Anti-Xa Activity Assays and Expected Peak–Trough Levels in an Asian Population: A Multicenter Study. Am J Cardiovasc Drugs 21, 669–679 (2021). https://doi.org/10.1007/s40256-021-00479-5

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  • DOI: https://doi.org/10.1007/s40256-021-00479-5

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