Risk Factors for Major Bleeding During Anticoagulation Therapy in Cancer-Associated Venous Thromboembolism ― From the COMMAND VTE Registry ―
Yuji Nishimoto, Yugo Yamashita, Kitae Kim, Takeshi Morimoto, Syunsuke Saga, Hidewo Amano, Toru Takase, Seiichi Hiramori, Maki Oi, Masaharu Akao, Yohei Kobayashi, Mamoru Toyofuku, Toshiaki Izumi, Tomohisa Tada, Po-Min Chen, Koichiro Murata, Yoshiaki Tsuyuki, Tomoki Sasa, Jiro Sakamoto, Minako Kinoshita, Kiyonori Togi, Hiroshi Mabuchi, Kensuke Takabayashi, Yusuke Yoshikawa, Hiroki Shiomi, Takao Kato, Takeru Makiyama, Koh Ono, Yukihito Sato, Takeshi Kimura, on behalf of the COMMAND VTE Registry Investigators
Abstract
BACKGROUND: Patients with cancer-associated venous thromboembolism (VTE) are at high risk for recurrent VTE and are recommended to receive prolonged anticoagulation therapy if they are at a low risk for bleeding. However, there are no established risk factors for bleeding during anticoagulation therapy. METHODS AND RESULTS: The COMMAND VTE Registry is a multicenter retrospective registry enrolling 3,027 consecutive patients with acute symptomatic VTE among 29 Japanese centers. The present study population consisted of 592 cancer-associated VTE patients with anticoagulation therapy. We constructed a multivariable Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the potential risk factors for major bleeding. During a median follow-up period of 199 days, major bleeding occurred in 72 patients. The cumulative incidence of major bleeding was 5.8% at 3 months, 13.8% at 1 year, 17.5% at 2 years, and 28.1% at 5 years. The most frequent major bleeding site was gastrointestinal tract (47%). Terminal cancer (adjusted HR, 4.17; 95% CI, 2.22-7.85, P<0.001), chronic kidney disease (adjusted HR, 1.89; 95% CI 1.06-3.37, P=0.031), and gastrointestinal cancer (adjusted HR, 1.78; 95% CI, 1.04-3.04, P=0.037) were independently associated with an increased risk of major bleeding. CONCLUSIONS: Major bleeding events were common during anticoagulation therapy in real-world cancer-associated VTE patients. Terminal cancer, chronic kidney disease, and gastrointestinal cancer were the independent risk factors for major bleeding.