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Background:  Real-world data on clinical characteristics and outcomes related to the use of different direct oral anticoagulants (DOACs) for cancer-associated venous thromboembolism (VTE) is lacking., Methods:  The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive patients with acute symptomatic VTE from 31 centers in Japan from January 2015 to August 2020. Our study population comprised 1,197 patients with active cancer who were divided into the edoxaban ( N  = 643, 54%), rivaroxaban ( N  = 297, 25%), and apixaban ( N  = 257, 22%) groups., Results:  The cumulative 5-year incidence of recurrent VTE (9.3, 10.2, and 8.5%, respectively, p  = 0.82) and all-cause death (67.5, 66.8, and 63.8%, respectively, p  = 0.22) did not differ among the groups. Despite adjusting for confounders, the risks of recurrent VTE and all-cause death did not differ significantly among the groups. The cumulative 5-year incidence of major and clinically relevant bleeding was significantly lower in the rivaroxaban group than those in the other groups (22.6, 14.0, and 22.8%, p  = 0.04; and 37.6, 26.8, and 38.3%, p  = 0.01, respectively). After adjusting for confounders, in the rivaroxaban group, the risk for major bleeding was numerically lower (hazard ratio [HR]: 0.65, 95% confidence interval [CI]: 0.40-1.01) and that of clinically relevant all bleeding was significantly lower (HR: 0.67, 95% CI: 0.48-0.92) than those in the edoxaban group., Conclusion:  The risks of recurrent VTE and all-cause death did not differ significantly among the different DOACs ; however, the risk of bleeding events could differ, with a potentially lower risk of bleeding with rivaroxaban., Competing Interests: Y.Y. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and grant support from Bayer Healthcare and Daiichi-Sankyo. T.M. 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. Y.N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. K.K. received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. N.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. S.I. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Y.O. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and research funds from Bayer Healthcare and Daiichi-Sankyo. K.T. received significant research grant from AMI Co., Ltd., Bayer Yakuhin, Ltd., Bristol-Myers K.K., EA Pharma Co., Ltd., MOCHIDA PHARMACEUTICAL CO., LTD., and scholarship fund from AMI Co., Ltd., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Edwards Lifesciences Corporation, Johnson & Johnson K.K., ONO PHARMACEUTICAL CO., LTD., Otsuka Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., and honoraria from Amgen K.K., Bayer Yakuhin, Ltd., Daiichi Sankyo Co., Ltd., Kowa Pharmaceutical Co. Ltd., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., and belongs to the endowed departments donated by Abbott Japan Co., Ltd., Boston Scientific Japan K.K., Fides-one, Inc., GM Medical Co., Ltd., ITI Co., Ltd., Kaneka Medix Co., Ltd., NIPRO CORPORATION, TERUMO Co, Ltd., Abbott Medical Co., Ltd., Cardinal Health Japan, Fukuda Denshi Co., Ltd., Japan Lifeline Co., Ltd., Medical Appliance Co., Ltd., Medtronic Japan Co., Ltd. All other authors have reported that they have no relationships relevant to the contents of this article to disclose., (Thieme. All rights reserved.)

Background: There is no established risk score for anticoagulant-related bleeding during the acute phase in patients with pulmonary embolism (PE). The PE-Syncope, Anemia, and Renal Dysfunction (PE-SARD) bleeding score was developed to predict early major bleeding but has not yet been fully externally validated., Objectives: To externally validate the PE-SARD bleeding score., Methods: Using the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) Registry-2 database, which enrolled 5197 consecutive acute symptomatic venous thromboembolism patients among 31 centers in Japan between January 2015 and August 2020, we identified acute PE patients. We divided them into 3 groups by the score: high-risk (>2.5 points), intermediate-risk (1-2.5 points), and low-risk (0 points). The discriminating and calibration performances of the score for 30-day major bleeding were assessed. Subgroup analyses based on active cancer were also performed., Results: Of 2781 eligible patients, the high-risk group accounted for 557 patients (20%), intermediate-risk group for 1412 (51%), and low-risk group for 812 (29%). Major bleeding occurred in 121 patients within 30 days. The cumulative 30-day incidence of major bleeding substantially increased in the higher risk categories by the score (high-risk group, 8.2% [95% CI, 5.9%-10.5%]; intermediate-risk group, 4.6% [95% CI, 3.5%-5.7%]; and low-risk group, 1.8% [95% CI, 0.8%-2.7%]). The discriminating power of the score was modest with a C statistic of 0.65 (95% CI, 0.61-0.70), with a good calibration performance with a score of <4 points, except for that in active cancer patients., Conclusion: The PE-SARD bleeding score had a modest discriminating performance with a limited calibration performance in acute PE patients without active cancer., Competing Interests: Declaration of competing interests Y.N. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo. Y.Y. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo, and grant support from Bayer Healthcare and Daiichi Sankyo. T.M. 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. K. Kaneda received lecture fees from Bristol Myers Squibb, Pfizer, and Daiichi Sankyo. N.I. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, and Daiichi Sankyo. S.I. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, and Daiichi Sankyo. Y.O. received lecture fees from Bayer Healthcare, Bristol Myers Squibb, Pfizer, and Daiichi Sankyo, and research funds from Bayer Healthcare and Daiichi Sankyo. N.K. received lecture fees from Bayer Healthcare and grant support from Pfizer. All other authors declare that they have no conflict of interest., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long-term outcomes from the warfarin era to the DOAC era., Methods and Results: We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010-2014) and Registry 2: 5197 patients in the DOAC era (2015-2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P <0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P =0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P =0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P =0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P =0.63)., Conclusions: Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.

Background: There have been still limited data on the transition of management strategies and clinical outcomes after introduction of direct oral anticoagulant (DOAC) for cancer-associated venous thromboembolism (VTE) in the real-world clinical practice., Methods: Using the 2 series of multicenter COMMAND VTE registries in Japan enrolling consecutive patients with acute symptomatic VTE, we compared 695 patients with cancer-associated VTE in the Registry-1 of the warfarin era and 1507 patients in the Registry-2 of the DOAC era., Results: Regarding oral anticoagulation therapy, 576 patients (82.9 %) in the Registry-1 received warfarin, whereas 1119 patients (79.6 %) in the Registry-2 received DOACs. The cumulative 3-year incidence of discontinuation of anticoagulation was not significantly different between the 2 registries (56.7 % vs. 62.7 %, P = 0.11). The cumulative 5-year incidence of recurrent VTE was significantly lower in the Registry-2 than in the Registry-1 (17.7 % vs. 10.1 %, P < 0.001). The cumulative 5-year incidence of major bleeding was significantly lower in the Registry-2 than in the Registry-1 (26.6 % vs. 20.4 %, P = 0.045). The proportion of gastrointestinal bleeding numerically increased from the Registry-1 to the Registry-2 (46.7 % and 49.5 %), whereas that of intracranial bleeding numerically decreased from the Registry-1 to the Registry-2 (17.1 % and 14.1 %)., Conclusions: In the current historical comparison of cancer-associated VTE between the 2 large real-world registries, there was a striking change in the treatment strategies with decreased risks of recurrent VTE and major bleeding in the DOAC era compared with those in the warfarin era, while there seemed to be unmet needs of DOAC-related gastrointestinal bleeding., Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htm UNIQUE IDENTIFIER: UMIN000044816., Competing Interests: Declaration of competing interest Dr. Yamashita received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo and grant support from Bayer Healthcare and Daiichi-Sankyo. Dr. Morimoto reports lecture 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. Kaneda received lecture fees from Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Nishimoto received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo. Dr. Ikeda N. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, and Daiichi-Sankyo. Dr. Ikeda S. received lecture fees from Bayer Healthcare, Bristol-Myers Squibb and Daiichi-Sankyo. All other authors report that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). 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. 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). 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. • There is limited data on the safety of DOACs in fragile patients with VTE. • Fragility was not associated with an increased risk of recurrent VTE. • Fragility showed a numerically higher rate of occurrence of major bleeding. • Fragility had a significantly increased risk of clinically relevant bleeding. [ABSTRACT FROM AUTHOR]