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Efficacy and Safety of Different Doses of Rivaroxaban and Risk Factors for Bleeding in Elderly Patients with Venous Thromboembolism: A Real-World, Multicenter, Observational, Cohort Study

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Abstract

Introduction

Venous thromboembolism (VTE) consists of deep vein thrombosis (DVT) and pulmonary embolism (PE). Rivaroxaban is a direct oral anticoagulant (DOAC) inhibiting activated coagulation factor X (FXa), and exerts several advantages in the treatment of VTE compared to conventional therapy. However, the efficacy and safety of rivaroxaban in elderly patients with VTE was still poorly understood.

Methods

The study was carried out using an observational and non-interventional approach. A total of 576 patients aged ≥ 60 years with newly diagnosed VTE were included in the study. All patients received rivaroxaban with recommended treatment duration of ≥ 3 months for secondary prevention. In addition, 535 elderly patients with various diseases except VTE were included in the study in a retrospective and randomized way.

Results

The total bleeding rate was 12.2% (70/576). Major bleeding and non-major clinically relevant (NMCR) bleeding occurred in 4 (0.69%) patients and 5 (0.87%) patients, respectively. The rate of recurrent VTE was 5.4%. The mean level of D-dimers was increased by 467.2% in the elderly patients with VTE compared with the elderly patients without VTE. The elderly patients with VTE receiving rivaroxaban at a dose of 10 mg once daily (n = 134) had lower risk for bleeding (3.7% vs 14.7%; P = 0.001) and a similar rate of recurrent VTE (4.5% vs 5.7%; P = 0.596) as compared to the elderly patients with VTE receiving rivaroxaban at higher doses including 15 mg once daily and 20 mg once daily (n = 442). In addition, age, concomitant aspirin, hemoglobin, activated partial thromboplastin time (APTT), and rivaroxaban doses were independent predictive factors for bleeding events.

Conclusions

The study suggested that a dose of 10 mg once daily should be the priority in elderly patients with VTE receiving long-term rivaroxaban anticoagulation therapy in view of reduced bleeding risk.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all the medical staff for providing us help in the collection of clinical data. The authors also thank all the participants of the study.

Funding

This work was supported by the Health Commission of Henan Province [grant number LHGJ20200577], and was sponsored by Henan provincial Medical Science and Technology Research Project [grant number LHGJ20200577]. The Rapid Service fee was funded by The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China.

Author information

Author notes

  1. Ke-Peng Lu, Qian-Qian Liao, and Ke-Wei Zhu have contributed equally to this work and share first authorship.

Authors and Affiliations

  1. Department of Pharmacy, The First Affiliated Hospital of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang, China

    Kepeng Lu

  2. Department of Pharmacy, People’s Hospital of Guilin, No.12 Civilization Road, Xiangshan District, Guilin, China

    Qian-Qian Liao, Hao Zhang, Qin Yu, Yang-Tao Dong & Qiu-Mian Wei

  3. Office of Pharmacovigilance, GuangZhou BaiYunShan Pharmaceutical Holdings CO., LTD. BaiYunShan Pharmaceutical General Factory, No. 88 Yunxiang Road Tonghe Street, Baiyun District, Guangzhou, 510515, Guangdong Province, China

    Ke-Wei Zhu

  4. Department of Clinical Pharmacology, Xiangya Hospital, Central South University, No. 110 Xiangya Road, Changsha, China

    Ke-Wei Zhu & Peng Chen

  5. Department of Pharmacy, People’s Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, No. 301 Zhengyuan North Street, Jinfeng District, Yinchuan, China

    Ying Yao

  6. Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32 West Second Section, 1st Ring Road, Qingyang District, Chengdu, China

    Xiao-Jiao Cui

  7. Department of Pharmacy, Nanchang Hongdu Hospital of TCM, No. 128 Xiangshan North Road, Donghu District, Nanchang, China

    Ying Bi

  8. Department of Pharmacy, The Affiliated Hospital of Southwest Medical University, No. 25 Taiping Street, Jiangyang District, Luzhou, China

    Meng Zhong

  9. Administration Office of Medication Clinical Trial, People’s Hospital of Guilin, No.12 Civilization Road, Xiangshan District, Guilin, China

    Jing-Cai Tang

  10. Department of Pharmacy, The Second Affiliated Hospital of Guilin Medical University, No. 212 Renmin Road, Lingui District, Guilin, China

    Jia-Kui Yue

  11. Department of Pharmacology, Renshou People’s Hospital, No. 177, Section 1, Longtan Avenue, Huairen Street, Renshou County, Meishan, China

    Hui He

  12. Department of Pharmacy, Affiliated Hospital of Guilin Medical University, No. 15 Lequn Road, Guilin, China

    Ze-Feng Zhu

  13. Department of Pharmacology, People’s Hospital of Qiandongnan Prefecture, No. 31 Shaoshan South Road, Kaili, Qiandongnan Miao and Dong Autonomous Prefecture, China

    Ze-Zheng Cai

  14. Department of Pharmacy, North China Medical Health Group Xingtai General Hospital, No. 202 Bayi Street, Xingtai, China

    Zhe Yang

  15. Department of Pharmacy, Yangquan Coal Industry (Group) General Hospital, No. 218 North Street, Mining Area, Yangquan, China

    Wei Zhang

  16. Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Henan University of Science and Technology, No. 24 Jinghua Road, Jianxi District, Luoyang, 471003, Henan Province, China

    Xuegai He

  17. Department of Pharmacy, The First Affiliated Hospital of Hainan Medical University, No.31 Longhua Road, Longhua District, Haikou, China

    Wei Zhang

Authors
  1. Kepeng Lu
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  2. Qian-Qian Liao
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  3. Ke-Wei Zhu
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  4. Ying Yao
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  6. Peng Chen
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  7. Ying Bi
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  20. Xuegai He
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Contributions

All authors contributed to the study conception and design. Kepeng Lu, Qian-Qian Liao, Ying Yao, Xiao-Jiao Cui, Ying Bi, Meng Zhong, Hao Zhang, Jing-Cai Tang, Qin Yu, Jia-Kui Yue, Hui He, Ze-Feng Zhu, Ze-Zheng Cai, Zhe Yang, Wei Zhang, Yang-Tao Dong, Qiu-Mian Wei were responsible for clinical data collection and follow-up. Among them, Kepeng Lu and Qian-Qian Liao were key contributors. Ke-Wei Zhu and Peng Chen were responsible for statistical analysis. Xuegai He was responsible for project administration and supervision. The first draft of the manuscript was written by Ke-Wei Zhu, Xuegai He were responsible for the modification and submission guidance, and the other co-authors revised it critically for important intellectual content. All authors reviewed the manuscript and agreed the final version of the article to be published. All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding authors

Correspondence to Ke-Wei Zhu or Xuegai He.

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Conflict of Interest

Author Ke-Wei Zhu is employed by Guangzhou Baiyunshan Pharmaceutical Holding Co., Ltd. Baiyunshan Pharmaceutical General Factory, Guangzhou, China. Author Zhe Yang is employed by the North China Medical Health Group Xingtai General Hospital, Xingtai, China. Author Wei Zhang was previously employed by the Yangquan Coal Industry (Group) General Hospital, Yangquan, China. Kepeng Lu, Qian-Qian Liao, Ying Yao, Xiao-Jiao Cui, Peng Chen, Ying Bi, Meng Zhong, Hao Zhang, Jing-Cai Tang, Qin Yu, Jia-Kui Yue, Hui He, Ze-Feng Zhu, Ze-Zheng Cai, Yang-Tao Dong, Qiu-Mian Wei, and Xuegai He declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical Approval

The study was performed in accordance with the Helsinki Declaration of 1964, and its later amendments. For the study involving the patients with VTE, it was firstly approved by the independent Medical Ethics Committee of the First Affiliated Hospital of Henan University of Science and Technology (No. 2022-03-B049), Luoyang, China. Then, the study was approved by the independent Medical Ethics Committee of People’s Hospital of Guilin (No. 2022013-KY), Guilin, China. Ultimately, each study was approved by the local ethics committee. All the patients with VTE provided verbal informed consent to participate in the study.

The clinical data of the patients without VTE were collected from electronic medical records (EMRs) in the People’s Hospital of Guilin. Written informed consent was waived in view of the non-interventional approach. The waiver and the study protocol were approved by the independent Medical Ethics Committee of People’s Hospital of Guilin (No. 2022-011KY).

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Lu, K., Liao, QQ., Zhu, KW. et al. Efficacy and Safety of Different Doses of Rivaroxaban and Risk Factors for Bleeding in Elderly Patients with Venous Thromboembolism: A Real-World, Multicenter, Observational, Cohort Study. Adv Ther 41, 391–412 (2024). https://doi.org/10.1007/s12325-023-02717-5

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