Risk Factors for Major Bleeding during Prolonged Anticoagulation Therapy in Patients with Venous Thromboembolism: From the COMMAND VTE Registry.

 There are limited data assessing the risk for bleeding on anticoagulation therapy beyond the acute phase in patients with venous thromboembolism (VTE). The present study aimed to identify risk factors for major bleeding during prolonged anticoagulation therapy in VTE patients.  The COMMAND VTE Registry is a multicenter registry enrolling 3,027 consecutive patients with acute symptomatic VTE. The current study population consisted of 2,728 patients who received anticoagulation therapy beyond the acute phase, after excluding those patients with major bleeding events (n = 48), death (n = 66), or loss to follow-up (n = 32) during the initial parenteral anticoagulation period within 10 days after diagnosis, and those without anticoagulation therapy beyond 10 days after diagnosis (n = 153).  During the median follow-up period of 555 days, major bleeding occurred in 189 patients (70 patients within 3 months; 119 patients beyond 3 months) with fatal bleeding in 24 patients (13%). The cumulative incidence of major bleeding was 2.7% at 3 months, 5.2% at 1 year, and 11.8% at 5 years. Active cancer (hazard ratio [HR], 3.06, 95% confidence interval [CI], 2.23-4.18), previous major bleeding (HR, 2.38, 95% CI, 1.51-3.59), anemia (HR, 1.75, 95% CI, 1.27-2.43), thrombocytopenia (HR, 2.11, 95% CI, 1.27-3.33), and age ≥75 years (HR, 1.64, 95% CI, 1.22-2.20) were independently associated with an increased risk for major bleeding by the multivariable Cox regression model.  Major bleeding events were not uncommon during prolonged anticoagulation therapy in real-world VTE patients. Active cancer, previous major bleeding, anemia, thrombocytopenia, and old age were the independent risk factors for major bleeding.

Kim K ，Yamashita Y ，Morimoto T ，Kitai T ，Yamane T ，Ehara N ，Kinoshita M ，Kaji S ，Amano H ，Takase T ，Hiramori S ，Oi M ，Akao M ，Kobayashi Y ，Toyofuku M ，Izumi T ，Tada T ，Chen PM ，Murata K ，Tsuyuki Y ，Saga S ，Sasa T ，Sakamoto J ，Kinoshita M ，Togi K ，Mabuchi H ，Takabayashi K ，Shiomi H ，Kato T ，Makiyama T ，Ono K ，Furukawa Y ，Kimura T ，COMMAND VTE Registry Investigators ... -  《-》

Risk Factors for Major Bleeding During Anticoagulation Therapy in Cancer-Associated Venous Thromboembolism　- From the COMMAND VTE Registry.

Nishimoto Y ，Yamashita Y ，Kim K ，Morimoto T ，Saga S ，Amano H ，Takase T ，Hiramori S ，Oi M ，Akao M ，Kobayashi Y ，Toyofuku M ，Izumi T ，Tada T ，Chen PM ，Murata K ，Tsuyuki Y ，Sasa T ，Sakamoto J ，Kinoshita M ，Togi K ，Mabuchi H ，Takabayashi K ，Yoshikawa Y ，Shiomi H ，Kato T ，Makiyama T ，Ono K ，Sato Y ，Kimura T ，COMMAND VTE Registry Investigators ... -  《-》

Risk factors of thrombotic recurrence and major bleeding in patients with intermediate-risk for recurrence of venous thromboembolism.

Prolonged anticoagulation therapy is recommended for patients with intermediate-risk for recurrence of venous thromboembolism (VTE). The current study aimed to identify risk factors of VTE recurrence and major bleeding in intermediate-risk patients. The COMMAND VTE Registry is a multicenter registry enrolled consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1703 patients with intermediate-risk for recurrence. The primary outcome measure was recurrent VTE during the entire follow-up period, and the secondary outcome measures were recurrent VTE and major bleeding during anticoagulation therapy. In the multivariable Cox regression model for recurrent VTE incorporating the status of anticoagulation therapy as a time-updated covariate, off-anticoagulation therapy was strongly associated with an increased risk for recurrent VTE (HR 9.42, 95% CI 5.97-14.86). During anticoagulation therapy, the independent risk factor for recurrent VTE was thrombophilia (HR 3.58, 95% CI 1.56-7.50), while the independent risk factors for major bleeding were age ≥ 75 years (HR 2.04, 95% CI 1.36-3.07), men (HR 1.52, 95% CI 1.02-2.27), history of major bleeding (HR 3.48, 95% CI 1.82-6.14) and thrombocytopenia (HR 3.73, 95% CI 2.04-6.37). Among VTE patients with intermediate-risk for recurrence, discontinuation of anticoagulation therapy was a very strong independent risk factor of recurrence during the entire follow-up period. The independent risk factors of recurrent VTE and those of major bleeding during anticoagulation therapy were different: thrombophilia for recurrent VTE, and advanced age, men, history of major bleeding, and thrombocytopenia for major bleeding. CLINICAL TRIAL REGISTRATION: Unique identifier: UMIN000021132. COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm .

Yamashita Y ，Amano H ，Morimoto T ，Kadota K ，Hata R ，Matsushita K ，Osakada K ，Sano A ，Takase T ，Hiramori S ，Kim K ，Oi M ，Akao M ，Kobayashi Y ，Toyofuku M ，Inoko M ，Tada T ，Chen PM ，Murata K ，Tsuyuki Y ，Nishimoto Y ，Sasa T ，Sakamoto J ，Kinoshita M ，Togi K ，Mabuchi H ，Takabayashi K ，Kato T ，Ono K ，Kimura T ，COMMAND VTE Registry Investigators ... -  《-》

Anticoagulation Therapy for Venous Thromboembolism in the Real World　- From the COMMAND VTE Registry.

Yamashita Y ，Morimoto T ，Amano H ，Takase T ，Hiramori S ，Kim K ，Konishi T ，Akao M ，Kobayashi Y ，Inoue T ，Oi M ，Izumi T ，Takahashi K ，Tada T ，Chen PM ，Murata K ，Tsuyuki Y ，Sakai H ，Saga S ，Sasa T ，Sakamoto J ，Yamada C ，Kinoshita M ，Togi K ，Ikeda T ，Ishii K ，Kaneda K ，Mabuchi H ，Otani H ，Takabayashi K ，Takahashi M ，Shiomi H ，Makiyama T ，Ono K ，Kimura T ，COMMAND VTE Registry Investigators ... -  《-》

Validation of the VTE-BLEED score's long-term performance for major bleeding in patients with venous thromboembolisms: From the COMMAND VTE registry.

The recently proposed VTE-BLEED score to predict the risk of major bleeding in patients with venous thromboembolisms (VTEs) on prolonged anticoagulation therapy was validated externally in randomized controlled trials and in a selected cohort, but not applied in non-selective cohorts. The present study aimed to evaluate the generalizability of the VTE-BLEED score in a non-selective cohort. The COMMAND VTE Registry is a multicenter retrospective registry enrolling consecutive patients with acute symptomatic VTEs among 29 centers in Japan. The present study population consisted of 2124 patients with prolonged anticoagulation therapy beyond 30 days, including 2008 (95%) patients with a first VTE episode and 1075 (51%) with unprovoked VTEs, who were divided into 1445 patients (68%) with a VTE-BLEED score of ≥2 (high-risk group) and 679 (32%) with a VTE-BLEED score of <2 (low-risk group). During a median follow-up period of 672 days, major bleeding events occurred in 121 patients. The cumulative 5-year incidence of major bleeding beyond 30 days was significantly higher in the high-risk group than low-risk group (13.2% versus 5.4%, P < .001). The hazard function curves demonstrated that the hazards of the high-risk group were consistently higher over time compared with the low-risk group, which suggested the long-term predictive ability of the score. In the present real-world VTE registry, the VTE-BLEED score had  a long-term predictive ability for high-risk patients with major bleeding during prolonged anticoagulation therapy, which could be useful in determining the optimal duration of anticoagulation therapy in individual patients.

Nishimoto Y ，Yamashita Y ，Morimoto T ，Saga S ，Amano H ，Takase T ，Hiramori S ，Kim K ，Oi M ，Akao M ，Kobayashi Y ，Yoshikawa Y ，Shiomi H ，Kato T ，Makiyama T ，Ono K ，Sato Y ，Kimura T ，COMMAND VTE Registry Group ... -  《-》