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Anticoagulation strategies and clinical outcomes after bleeding events during anticoagulation therapy for venous thromboembolism in the practice-based Japanese registry

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Abstract

There is a paucity of data on anticoagulation strategies and clinical outcomes after bleeding events for venous thromboembolism (VTE). In a multicenter Japanese registry enrolling 3027 patients with acute symptomatic VTE, after excluding 430 patients with thrombolysis and 207 patients without anticoagulation therapy, the current study population consisted of 2390 patients, who were divided into patients with major bleeding, clinically relevant non-major (CRNM) bleeding and no bleeding during anticoagulation therapy. All-cause death at 90 days after the bleeding events was evaluated as the primary outcome. There were 189 patients with major bleeding, 147 patients with CRNM bleeding, and 2054 patients without bleeding. Among 189 patients with major bleeding, 142 patients (75%) discontinued anticoagulants, of whom patients with temporary discontinuation and those with permanent discontinuation accounted for 63 patients (44%) and 79 patients (56%), and 58 patients (30.7%) died within 90 days after the bleeding events. The multivariable logistic regression model among patients with bleeding events revealed that active cancer and bleeding events within 90 days after VTE diagnosis were independently associated with 90-day mortality after the bleeding events (active cancer: OR 5.05, 95%CI 2.82–9.05; bleeding events within 90 days after VTE diagnosis: OR 2.23, 95%CI 1.25–3.96). In this practice-based large registry, anticoagulants were frequently discontinued in patients who experienced major bleeding events during anticoagulation therapy and nearly half of them restarted anticoagulants with mortality rate of approximately 30% within 90 days after the bleeding events, and active cancer was the most prevalent cause of death.

Clinical trial registration COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000021132.

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Acknowledgements

We appreciate the support and collaboration of the co-investigators participating in the COMMAND VTE Registry. We are indebted to the independent clinical research organization (Research Institute for Production Development, Kyoto, Japan) for technical support.

Funding

The COMMAND VTE Registry is supported by the independent clinical research organization (Research Institute for Production Development, Kyoto, Japan) and research funding from Mitsubishi Tanabe Pharma Corporation. The research funding had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto, 606-8507, Japan

    Yugo Yamashita, Takao Kato, Koh Ono & Takeshi Kimura

  2. Department of Clinical Epidemiology, Hyogo College of Medicine, Nishinomiya, Japan

    Takeshi Morimoto

  3. Department of Medicine, Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, The Netherlands

    Frederikus A. Klok

  4. Center for Thrombosis and Hemostasis, University Medical Center, Mainz, Germany

    Frederikus A. Klok & Stefano Barco

  5. Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland

    Stefano Barco

  6. Department of Cardiology, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki, Japan

    Yuji Nishimoto

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  1. Yugo Yamashita
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  2. Takeshi Morimoto
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  3. Frederikus A. Klok
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  7. Koh Ono
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the COMMAND VTE Registry Investigators

Contributions

YY, FK, SB contributed to the design of the study, the analysis and interpretation of data, and drafted the manuscript. TM and TK contributed to the analysis and interpretation of data, and drafted the manuscript. All other authors contributed to acquisition and interpretation of data, and reviewed the manuscript.

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Correspondence to Yugo Yamashita.

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Conflict of interest

Dr. Yamashita received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, and Bayer Healthcare. Dr Morimoto reports lecturer's fees from Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Kowa, Kyocera, Novartis, and Toray; manuscript fees from Bristol-Myers Squibb and Kowa; advisory board for Sanofi. Dr. Klok reports research grants from Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, MSD, Daiichi-Sankyo, Actelion, the Dutch thrombosis association, The Netherlands Organization for Health Research and Development and the Dutch Heart foundation, all outside the current work. Dr. Nishimoto received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, and Bayer Healthcare. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For the COMMAND VTE Registry of retrospective study formal consent is not required.

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Yamashita, Y., Morimoto, T., Klok, F.A. et al. Anticoagulation strategies and clinical outcomes after bleeding events during anticoagulation therapy for venous thromboembolism in the practice-based Japanese registry. J Thromb Thrombolysis 54, 524–534 (2022). https://doi.org/10.1007/s11239-022-02665-x

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