Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era

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 D...

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Main Authors: Kazuhisa Kaneda, Yugo Yamashita, Takeshi Morimoto, Ryuki Chatani, Yuji Nishimoto, Nobutaka Ikeda, Yohei Kobayashi, Satoshi Ikeda, Kitae Kim, Moriaki Inoko, Toru Takase, Shuhei Tsuji, Maki Oi, Takuma Takada, Kazunori Otsui, Jiro Sakamoto, Yoshito Ogihara, Takeshi Inoue, Shunsuke Usami, Po‐Min Chen, Kiyonori Togi, Norimichi Koitabashi, Seiichi Hiramori, Kosuke Doi, Hiroshi Mabuchi, Yoshiaki Tsuyuki, Koichiro Murata, Kensuke Takabayashi, Hisato Nakai, Daisuke Sueta, Wataru Shioyama, Tomohiro Dohke, Ryusuke Nishikawa, Koh Ono, Takeshi Kimura
Format: Article
Language:English
Published: Wiley 2024-08-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.034412
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author Kazuhisa Kaneda
Yugo Yamashita
Takeshi Morimoto
Ryuki Chatani
Yuji Nishimoto
Nobutaka Ikeda
Yohei Kobayashi
Satoshi Ikeda
Kitae Kim
Moriaki Inoko
Toru Takase
Shuhei Tsuji
Maki Oi
Takuma Takada
Kazunori Otsui
Jiro Sakamoto
Yoshito Ogihara
Takeshi Inoue
Shunsuke Usami
Po‐Min Chen
Kiyonori Togi
Norimichi Koitabashi
Seiichi Hiramori
Kosuke Doi
Hiroshi Mabuchi
Yoshiaki Tsuyuki
Koichiro Murata
Kensuke Takabayashi
Hisato Nakai
Daisuke Sueta
Wataru Shioyama
Tomohiro Dohke
Ryusuke Nishikawa
Koh Ono
Takeshi Kimura
author_facet Kazuhisa Kaneda
Yugo Yamashita
Takeshi Morimoto
Ryuki Chatani
Yuji Nishimoto
Nobutaka Ikeda
Yohei Kobayashi
Satoshi Ikeda
Kitae Kim
Moriaki Inoko
Toru Takase
Shuhei Tsuji
Maki Oi
Takuma Takada
Kazunori Otsui
Jiro Sakamoto
Yoshito Ogihara
Takeshi Inoue
Shunsuke Usami
Po‐Min Chen
Kiyonori Togi
Norimichi Koitabashi
Seiichi Hiramori
Kosuke Doi
Hiroshi Mabuchi
Yoshiaki Tsuyuki
Koichiro Murata
Kensuke Takabayashi
Hisato Nakai
Daisuke Sueta
Wataru Shioyama
Tomohiro Dohke
Ryusuke Nishikawa
Koh Ono
Takeshi Kimura
author_sort Kazuhisa Kaneda
collection DOAJ
description 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.
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spelling doaj-art-5df8e7cb04aa414a9116a7c9beda522d2025-08-20T02:12:01ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-08-01131510.1161/JAHA.124.034412Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant EraKazuhisa Kaneda0Yugo Yamashita1Takeshi Morimoto2Ryuki Chatani3Yuji Nishimoto4Nobutaka Ikeda5Yohei Kobayashi6Satoshi Ikeda7Kitae Kim8Moriaki Inoko9Toru Takase10Shuhei Tsuji11Maki Oi12Takuma Takada13Kazunori Otsui14Jiro Sakamoto15Yoshito Ogihara16Takeshi Inoue17Shunsuke Usami18Po‐Min Chen19Kiyonori Togi20Norimichi Koitabashi21Seiichi Hiramori22Kosuke Doi23Hiroshi Mabuchi24Yoshiaki Tsuyuki25Koichiro Murata26Kensuke Takabayashi27Hisato Nakai28Daisuke Sueta29Wataru Shioyama30Tomohiro Dohke31Ryusuke Nishikawa32Koh Ono33Takeshi Kimura34Department of Cardiovascular Medicine, Graduate School of Medicine Kyoto University Kyoto JapanDepartment of Cardiovascular Medicine, Graduate School of Medicine Kyoto University Kyoto JapanDepartment of Clinical Epidemiology Hyogo College of Medicine Nishinomiya JapanDepartment of Cardiovascular Medicine Kurashiki Central Hospital Kurashiki JapanDepartment of Cardiology Hyogo Prefectural Amagasaki General Medical Center Amagasaki JapanDivision of Cardiovascular Medicine Toho University Ohashi Medical Center Tokyo JapanDepartment of Cardiovascular Center Osaka Red Cross Hospital Osaka JapanDepartment of Cardiovascular Medicine Nagasaki University Graduate School of Biomedical Sciences Nagasaki JapanDepartment of Cardiovascular Medicine Kobe City Medical Center General Hospital Kobe JapanCardiovascular Center The Tazuke Kofukai Medical Research Institute, Kitano Hospital Osaka JapanDepartment of Cardiology Kinki University Hospital Osaka JapanDepartment of Cardiology Japanese Red Cross Wakayama Medical Center Wakayama JapanDepartment of Cardiology Japanese Red Cross Otsu Hospital Otsu JapanDepartment of Cardiology Tokyo Women’s Medical University Tokyo JapanDepartment of General Internal Medicine Kobe University Hospital Kobe JapanDepartment of Cardiology Tenri Hospital Tenri JapanDepartment of Cardiology and Nephrology Mie University Graduate School of Medicine Tsu JapanDepartment of Cardiology Shiga General Hospital Moriyama JapanDepartment of Cardiology Kansai Electric Power Hospital Osaka JapanDepartment of Cardiology Osaka Saiseikai Noe Hospital Osaka JapanDivision of Cardiology, Nara Hospital Kinki University Faculty of Medicine Ikoma JapanDepartment of Cardiovascular Medicine Gunma University Graduate School of Medicine Maebashi JapanDepartment of Cardiology Kokura Memorial Hospital Kokura JapanDepartment of Cardiology National Hospital Organization Kyoto Medical Center Kyoto JapanDepartment of Cardiology Koto Memorial Hospital Higashiomi JapanDivision of Cardiology Shimada General Medical Center Shimada JapanDepartment of Cardiology Shizuoka City Shizuoka Hospital Shizuoka JapanDepartment of Cardiology Hirakata Kohsai Hospital Hirakata JapanDepartment of Cardiovascular Medicine Sugita Genpaku Memorial Obama Municipal Hospital Obama JapanDepartment of Cardiovascular Medicine, Graduate School of Medical Sciences Kumamoto University Kumamoto JapanDepartment of Cardiovascular Medicine Shiga University of Medical Science Otsu JapanDivision of Cardiology Kohka Public Hospital Koka JapanDepartment of Cardiovascular Medicine, Graduate School of Medicine Kyoto University Kyoto JapanDepartment of Cardiovascular Medicine, Graduate School of Medicine Kyoto University Kyoto JapanDepartment of Cardiology Hirakata Kohsai Hospital Hirakata JapanBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.124.034412direct oral anticoagulantmajor bleedingoutcomerecurrencevenous thromboembolismwarfarin
spellingShingle Kazuhisa Kaneda
Yugo Yamashita
Takeshi Morimoto
Ryuki Chatani
Yuji Nishimoto
Nobutaka Ikeda
Yohei Kobayashi
Satoshi Ikeda
Kitae Kim
Moriaki Inoko
Toru Takase
Shuhei Tsuji
Maki Oi
Takuma Takada
Kazunori Otsui
Jiro Sakamoto
Yoshito Ogihara
Takeshi Inoue
Shunsuke Usami
Po‐Min Chen
Kiyonori Togi
Norimichi Koitabashi
Seiichi Hiramori
Kosuke Doi
Hiroshi Mabuchi
Yoshiaki Tsuyuki
Koichiro Murata
Kensuke Takabayashi
Hisato Nakai
Daisuke Sueta
Wataru Shioyama
Tomohiro Dohke
Ryusuke Nishikawa
Koh Ono
Takeshi Kimura
Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
direct oral anticoagulant
major bleeding
outcome
recurrence
venous thromboembolism
warfarin
title Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era
title_full Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era
title_fullStr Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era
title_full_unstemmed Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era
title_short Temporal Changes in Long‐Term Outcomes of Venous Thromboembolism From the Warfarin Era to the Direct Oral Anticoagulant Era
title_sort temporal changes in long term outcomes of venous thromboembolism from the warfarin era to the direct oral anticoagulant era
topic direct oral anticoagulant
major bleeding
outcome
recurrence
venous thromboembolism
warfarin
url https://www.ahajournals.org/doi/10.1161/JAHA.124.034412
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