D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis

Abstract: Cancer-associated isolated distal deep vein thrombosis (IDDVT) is a common complication in patients with cancer. The Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients with Cancer study revealed the superiority of 12- over 3-month edoxaban trea...

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Main Authors: Tatsuya Nishikawa, Yugo Yamashita, Masashi Fujita, Takeshi Morimoto, Nao Muraoka, Michihisa Umetsu, Yuji Nishimoto, Takuma Takada, Yoshito Ogihara, Nobutaka Ikeda, Kazunori Otsui, Daisuke Sueta, Yukari Tsubata, Masaaki Shoji, Ayumi Shikama, Yutaka Hosoi, Yasuhiro Tanabe, Ryuki Chatani, Kengo Tsukahara, Naohiko Nakanishi, Kitae Kim, Satoshi Ikeda, Taku Yasui, Hironori Yamamoto, Koh Ono, Takeshi Kimura
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Blood Vessels, Thrombosis & Hemostasis
Online Access:http://www.sciencedirect.com/science/article/pii/S2950327225000208
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author Tatsuya Nishikawa
Yugo Yamashita
Masashi Fujita
Takeshi Morimoto
Nao Muraoka
Michihisa Umetsu
Yuji Nishimoto
Takuma Takada
Yoshito Ogihara
Nobutaka Ikeda
Kazunori Otsui
Daisuke Sueta
Yukari Tsubata
Masaaki Shoji
Ayumi Shikama
Yutaka Hosoi
Yasuhiro Tanabe
Ryuki Chatani
Kengo Tsukahara
Naohiko Nakanishi
Kitae Kim
Satoshi Ikeda
Taku Yasui
Hironori Yamamoto
Koh Ono
Takeshi Kimura
author_facet Tatsuya Nishikawa
Yugo Yamashita
Masashi Fujita
Takeshi Morimoto
Nao Muraoka
Michihisa Umetsu
Yuji Nishimoto
Takuma Takada
Yoshito Ogihara
Nobutaka Ikeda
Kazunori Otsui
Daisuke Sueta
Yukari Tsubata
Masaaki Shoji
Ayumi Shikama
Yutaka Hosoi
Yasuhiro Tanabe
Ryuki Chatani
Kengo Tsukahara
Naohiko Nakanishi
Kitae Kim
Satoshi Ikeda
Taku Yasui
Hironori Yamamoto
Koh Ono
Takeshi Kimura
author_sort Tatsuya Nishikawa
collection DOAJ
description Abstract: Cancer-associated isolated distal deep vein thrombosis (IDDVT) is a common complication in patients with cancer. The Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients with Cancer study revealed the superiority of 12- over 3-month edoxaban treatment with respect to thrombotic risk. However, it remains unclear whether D-dimer levels during anticoagulation influence the efficacy of extended anticoagulation. In this post hoc subgroup analysis, we stratified 519 patients into the low D-dimer (<1.0 μg/mL) (n = 308) and high D-dimer (≥1.0 μg/mL) (n = 211) subgroups based on D-dimer levels at 3 months. The cumulative incidence of a composite of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death was lower in the 12-month edoxaban group than in the 3-month edoxaban group in both the low D-dimer (0.8% vs 5.6%; P = .02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.66) and high D-dimer (0.9% vs 10.2%; P = .01; OR, 0.11; 95% CI, 0.01-0.62) subgroups without interaction. Furthermore, there was no significant difference in the cumulative incidence of major bleeding between the 12- and 3-month groups in both the low D-dimer (3.6% vs 1.8%; P = .64; OR, 1.96; 95% CI, 0.47-9.67) and high D-dimer (18.3% vs 14.6%; P = .29; OR, 1.27; 95% CI, 0.60-2.75) subgroups without interaction. In conclusion, a 12-month edoxaban treatment for cancer-associated IDDVT was superior to a 3-month treatment in reducing thrombotic events, irrespective of D-dimer levels after 3 months of anticoagulation therapy. There was no significant increased risk of major bleeding in the 12-month edoxaban group relative to the 3-month edoxaban group regardless of the D-dimer levels at 3 months. This trial was registered at www.clinicaltrials.gov as #NCT03895502.
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spelling doaj-art-7f9f7e7a5a5d400d9a6a48eca8cc5ddf2025-08-20T02:16:50ZengElsevierBlood Vessels, Thrombosis & Hemostasis2950-32722025-05-012210006310.1016/j.bvth.2025.100063D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosisTatsuya Nishikawa0Yugo Yamashita1Masashi Fujita2Takeshi Morimoto3Nao Muraoka4Michihisa Umetsu5Yuji Nishimoto6Takuma Takada7Yoshito Ogihara8Nobutaka Ikeda9Kazunori Otsui10Daisuke Sueta11Yukari Tsubata12Masaaki Shoji13Ayumi Shikama14Yutaka Hosoi15Yasuhiro Tanabe16Ryuki Chatani17Kengo Tsukahara18Naohiko Nakanishi19Kitae Kim20Satoshi Ikeda21Taku Yasui22Hironori Yamamoto23Koh Ono24Takeshi Kimura25Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, Japan; Department of Cardiology, Akashi Medical Center, Akashi, JapanDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Correspondence: Yugo Yamashita, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan;Department of Onco-Cardiology, Osaka International Cancer Institute, Osaka, Japan; Masashi Fujita, Department of Onco-Cardiology, Osaka International Cancer Institute, 3-1-69 Otemae, Chuo-ku, Osaka 541-8567, Japan;Department of Clinical Epidemiology, Hyogo Medical University, Nishinomiya, JapanDivision of Cardiology, Shizuoka Cancer Center, Nagaizumi, JapanDivision of Vascular Surgery, Department of Surgery, Tohoku University Hospital, Sendai, JapanDivision of Cardiology, Osaka General Medical Center, Osaka, JapanDepartment of Cardiology, Tokyo Women’s Medical University, Tokyo, JapanDepartment of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu, JapanDivision of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, JapanDepartment of General Internal Medicine, Kobe University Graduate School of Medicine, Kobe, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, JapanDivision of Medical Oncology and Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, JapanDepartment of Cardiovascular Medicine, National Cancer Center Hospital, Tokyo, JapanDepartment of Obstetrics and Gynecology, Faculty of Medicine, University of Tsukuba, Tsukuba, JapanDepartment of Cardiovascular Surgery, Kyorin University Faculty of Medicine, Tokyo, JapanDepartment of Cardiology, St. Marianna University School of Medicine, Kawasaki, JapanDepartment of Cardiovascular Medicine, Kurashiki Central Hospital, Kurashiki, JapanDivision of Cardiology, Fujisawa City Hospital, Fujisawa, JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, JapanDepartment of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, JapanDepartment of Cardiovascular Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Onco-Cardiology, Osaka International Cancer Institute, Osaka, JapanDepartment of Onco-Cardiology, Osaka International Cancer Institute, Osaka, JapanDepartment of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, JapanDepartment of Cardiology, Hirakata Kohsai Hospital, Hirakata, JapanAbstract: Cancer-associated isolated distal deep vein thrombosis (IDDVT) is a common complication in patients with cancer. The Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients with Cancer study revealed the superiority of 12- over 3-month edoxaban treatment with respect to thrombotic risk. However, it remains unclear whether D-dimer levels during anticoagulation influence the efficacy of extended anticoagulation. In this post hoc subgroup analysis, we stratified 519 patients into the low D-dimer (<1.0 μg/mL) (n = 308) and high D-dimer (≥1.0 μg/mL) (n = 211) subgroups based on D-dimer levels at 3 months. The cumulative incidence of a composite of symptomatic recurrent venous thromboembolism (VTE) or VTE-related death was lower in the 12-month edoxaban group than in the 3-month edoxaban group in both the low D-dimer (0.8% vs 5.6%; P = .02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.66) and high D-dimer (0.9% vs 10.2%; P = .01; OR, 0.11; 95% CI, 0.01-0.62) subgroups without interaction. Furthermore, there was no significant difference in the cumulative incidence of major bleeding between the 12- and 3-month groups in both the low D-dimer (3.6% vs 1.8%; P = .64; OR, 1.96; 95% CI, 0.47-9.67) and high D-dimer (18.3% vs 14.6%; P = .29; OR, 1.27; 95% CI, 0.60-2.75) subgroups without interaction. In conclusion, a 12-month edoxaban treatment for cancer-associated IDDVT was superior to a 3-month treatment in reducing thrombotic events, irrespective of D-dimer levels after 3 months of anticoagulation therapy. There was no significant increased risk of major bleeding in the 12-month edoxaban group relative to the 3-month edoxaban group regardless of the D-dimer levels at 3 months. This trial was registered at www.clinicaltrials.gov as #NCT03895502.http://www.sciencedirect.com/science/article/pii/S2950327225000208
spellingShingle Tatsuya Nishikawa
Yugo Yamashita
Masashi Fujita
Takeshi Morimoto
Nao Muraoka
Michihisa Umetsu
Yuji Nishimoto
Takuma Takada
Yoshito Ogihara
Nobutaka Ikeda
Kazunori Otsui
Daisuke Sueta
Yukari Tsubata
Masaaki Shoji
Ayumi Shikama
Yutaka Hosoi
Yasuhiro Tanabe
Ryuki Chatani
Kengo Tsukahara
Naohiko Nakanishi
Kitae Kim
Satoshi Ikeda
Taku Yasui
Hironori Yamamoto
Koh Ono
Takeshi Kimura
D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis
Blood Vessels, Thrombosis & Hemostasis
title D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis
title_full D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis
title_fullStr D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis
title_full_unstemmed D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis
title_short D-dimer after 3 months of anticoagulation therapy and outcomes in cancer-associated isolated distal deep vein thrombosis
title_sort d dimer after 3 months of anticoagulation therapy and outcomes in cancer associated isolated distal deep vein thrombosis
url http://www.sciencedirect.com/science/article/pii/S2950327225000208
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