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Multicenter Study
. 2025 Jun;58(5):591-600.
doi: 10.1007/s11239-025-03105-2. Epub 2025 May 28.

Edoxaban treatment without initial heparin lead-in for acute venous thromboembolism: insight from the COMMAND VTE registry-2

Yuta Tsujisaka  1 , Yugo Yamashita  2   3 , Takeshi Morimoto  4 , Ryuki Chatani  5 , Kazuhisa Kaneda  1 , Yuji Nishimoto  6 , Nobutaka Ikeda  7 , Yohei Kobayashi  8 , Satoshi Ikeda  9 , Kitae Kim  10 , Moriaki Inoko  11 , Toru Takase  12 , Shuhei Tsuji  13 , Maki Oi  14 , Takuma Takada  15 , Kazunori Otsui  16 , Jiro Sakamoto  17 , Yoshito Ogihara  18 , Takeshi Inoue  19 , Shunsuke Usami  20 , Po-Min Chen  21 , Kiyonori Togi  22 , Norimichi Koitabashi  23 , Seiichi Hiramori  24 , Kosuke Doi  25 , Hiroshi Mabuchi  26 , Yoshiaki Tsuyuki  27 , Koichiro Murata  28 , Kensuke Takabayashi  29 , Hisato Nakai  30 , Daisuke Sueta  31 , Wataru Shioyama  32 , Tomohiro Dohke  33 , Ryusuke Nishikawa  1 , Koh Ono  1 , Takeshi Kimura  29 ; COMMAND VTE Registry-2 Investigators
Affiliations
Multicenter Study

Edoxaban treatment without initial heparin lead-in for acute venous thromboembolism: insight from the COMMAND VTE registry-2

Yuta Tsujisaka et al. J Thromb Thrombolysis. 2025 Jun.

Abstract

The package insert of edoxaban for acute venous thromboembolism (VTE) recommended administration following initial parenteral anticoagulation including heparin. We explored the effectiveness and safety of edoxaban for acute VTE without initial heparin lead-in treatment. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients in Japan between January 2015 and August 2020. The current study population consisted of 1842 patients with acute VTE treated with edoxaban. The baseline characteristics and clinical outcomes were compared between the 2 groups with or without initial heparin lead-in treatment stratified by pulmonary embolism (PE) (848 patients) and deep vein thrombosis (DVT) only (994 patients). Propensity score (PS) matching analysis was performed to balance potential baseline differences. PE and DVT patients without heparin lead-in treatment accounted for 225 (27%) and 750 (75%), respectively. PS matching provided 195 pairs of PE patients and 224 pairs of DVT patients. There was no significant difference between the no heparin and heparin groups in the cumulative 30-day incidence of all-cause death (PE: 2.6% vs. 4.2%, P = 0.40; DVT: 2.7% vs. 3.2%, P = 0.78) and a composite of all-cause death, recurrent VTE, or major bleeding (PE: 5.8% vs. 8.4%, P = 0.32; DVT: 4.6% vs. 6.4%, P = 0.41). In the current real-world VTE registry, a substantial proportion of patients with acute VTE were treated with edoxaban without initial heparin lead-in treatment. There was no obvious signal suggesting worse short-term clinical outcomes with edoxaban treatment without versus with initial heparin lead-in treatment.

Keywords: Edoxaban; Heparin; Lead-in; Outcome; Venous thromboembolism.

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Conflict of interest statement

Declarations. 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 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. 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. Dr. Ogihara received lecture fees from Bayer Healthcare, Bristol-Myers Squibb, Pfizer, and Daiichi-Sankyo, and a research fund from Bayer Healthcare. Dr. Koitabashi received lecture fees from Bayer Healthcare and grant support from Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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