Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.

Introduction: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE).
Materials and Methods: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg.
Results: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41).
Conclusions: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yoshito Ogihara reports a relationship with Bayer Healthcare that includes: funding grants and speaking and lecture fees. Yoshito Ogihara reports a relationship with Daiichi Sankyo Co Ltd. that includes: funding grants and speaking and lecture fees. Yoshito Ogihara reports a relationship with Bristol Myers Squibb that includes: speaking and lecture fees. Yoshito Ogihara reports a relationship with Pfizer that includes: speaking and lecture fees. Yugo Yamashita reports a relationship with Bayer Healthcare that includes: funding grants and speaking and lecture fees. Yugo Yamashita reports a relationship with Daiichi-Sankyo that includes: funding grants and speaking and lecture fees. Yugo Yamashita reports a relationship with Bristol Myers Squibb that includes: speaking and lecture fees. Yugo Yamashita reports a relationship with Pfizer that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Daiichi Sankyo that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Japan Lifeline that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Kowa that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Kyocera that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Novartis that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Toray that includes: speaking and lecture fees. Takeshi Morimoto reports a relationship with Sanofi that includes: consulting or advisory. Kazuhisa Kaneda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Kazuhisa Kaneda reports a relationship with Pfizer that includes: speaking and lecture fees. Kazuhisa Kaneda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Pfizer that includes: speaking and lecture fees. Yuji Nishimoto reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Nobutaka Ikeda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Satoshi Ikeda reports a relationship with Daiichi-Sankyo that includes: speaking and lecture fees. Norimichi Koitabashi reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Norimichi Koitabashi reports a relationship with Pfizer that includes: funding grants. Kaoru Dohi reports a relationship with Bayer Healthcare that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Bristol-Myers Squibb that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Pfizer that includes: speaking and lecture fees. Kaoru Dohi reports a relationship with Daiichi Sankyo that includes: funding grants and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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