Use of direct oral anti-coagulants for the treatment of venous thromboembolism in patients with advanced cancer: a prospective observational study

  • Takuya OyakawaEmail author
  • Nao Muraoka
  • Kei Iida
  • Masatoshi Kusuhara
  • Keita Mori
Original Article



The efficacy of direct oral anti-coagulants (DOACs) for the treatment of venous thromboembolism (VTE) in Japanese patients with advanced cancer is largely unknown.


This prospective single-center observational study enrolled Japanese patients with unresectable advanced cancer who started DOAC treatment for new-onset VTE between December 2015 and May 2018. Patients were followed for 3 months to evaluate bleeding and VTE recurrences. The primary study endpoint was major and non-major bleeding.


One hundred and forty-five of 147 enrolled patients were analyzed. Of these, 8 [5.5%, 95% confidence interval (CI) 2.8–10.5] and 29 patients (20%, 95% CI 14.3–27.2) experienced major and non-major bleeding, respectively. Patients with bleeding were more likely to have a poor performance status (PS) [hazard rate (HR) 2.04, 95% CI 1.15–3.63] and more frequent use of non-steroidal anti-inflammatory drugs (NSAIDs) (HR 2.75, 95% CI 1.62–4.67) relative to those without bleeding. In a multivariate analysis, combined DOAC and NSAID use correlated significantly with bleeding (odds ratio 4.63, 95% CI 1.70–12.9, p = 0.003). Among 105 of 145 patients included in the VTE recurrence assessment, 9 experienced a VTE recurrence (8.6%, 95% CI 4.6–15.5).


Our findings confirm the risk of bleeding during DOAC treatment for VTE in Japanese patients with advanced cancer, particularly those with poor PS and those using NSAIDs. The risk of bleeding in these patients may be reduced by avoiding the combined use of DOACs and NSAIDs.


Advanced cancer Venous thromboembolism Pulmonary thromboembolism Direct oral anti-coagulant Bleeding Cardio-oncology 



This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Japan Society of Clinical Oncology 2019

Authors and Affiliations

  • Takuya Oyakawa
    • 1
    Email author
  • Nao Muraoka
    • 1
  • Kei Iida
    • 1
  • Masatoshi Kusuhara
    • 2
  • Keita Mori
    • 3
  1. 1.Division of CardiologyShizuoka Cancer CenterShizuokaJapan
  2. 2.Research InstituteShizuoka Cancer CenterShizuokaJapan
  3. 3.Clinical Research Promotion Unit, Clinical Research Support CenterShizuoka Cancer CenterShizuokaJapan

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