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Randomized Controlled Trial
. 2024 Jan 30;149(5):406-409.
doi: 10.1161/CIRCULATIONAHA.123.067528. Epub 2023 Nov 13.

A Multicenter, Single-Blind, Randomized, Warfarin-Controlled Trial of Edoxaban in Patients With Chronic Thromboembolic Pulmonary Hypertension: KABUKI Trial

Kazuya Hosokawa  1 , Hiroko Watanabe  2 , Yu Taniguchi  3 , Nobutaka Ikeda  4 , Takumi Inami  5 , Satoshi Yasuda  6 , Toyoaki Murohara  7 , Masaru Hatano  8 , Yuichi Tamura  9 , Jun Yamashita  10 , Koichiro Tatsumi  11 , Ichizo Tsujino  12 , Yuko Kobayakawa  2 , Shiro Adachi  7 , Nobuhiro Yaoita  6 , Shun Minatsuki  8 , Koji Todaka  2 , Keiichi Fukuda  13 , Hiroyuki Tsutsui #  14 , Kohtaro Abe #  1 ; KABUKI Investigators
Affiliations
Randomized Controlled Trial

A Multicenter, Single-Blind, Randomized, Warfarin-Controlled Trial of Edoxaban in Patients With Chronic Thromboembolic Pulmonary Hypertension: KABUKI Trial

Kazuya Hosokawa et al. Circulation. .
No abstract available

Keywords: anticoagulants; factor Xa Inhibitors; hypertension, pulmonary; randomized controlled trial; thromboembolism; warfarin.

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Conflict of interest statement

Disclosures Dr Hosokawa reports personal fees from Janssen Pharmaceutical, Bayer Yakuhin, Nippon Shinyaku, and Pfizer, outside the submitted work. Dr Taniguchi reports grants from Janssen Pharmaceutical and Nippon Shinyaku; and personal fees from Janssen Pharmaceutical and Nippon Shinyaku, outside the submitted work. Dr Ikeda reports personal fees from Daiichi-Sankyo, Bayer Yakuhin, and Bristol-Myers Squibb, outside the submitted work. Dr Inami reports personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Murohara reports a grant and personal fees from Daiichi Sankyo, outside the submitted work. Dr Hatano reports a grant from Japan Agency for Medical Research and Development and personal fees from Janssen Pharmaceutical and Bayer Yakuhin, outside the submitted work. Dr Tamura reports grants from Bayer Yakuhin, Nippon Shinyaku, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Nippon Shinyaku, Daiichi Sankyo, and Janssen Pharmaceutical, outside the submitted work. Dr Yamashita reports a grant from Abbott Vascular Japan; and personal fees from Kaneka Medix, Boston Scientific Japan, Nihon Kohden, Philips Japan, Janssen Pharmaceutical, and Bayer Yakuhin, outside the submitted work. Dr Tsujino reports personal fees from Janssen Pharmaceutical and Nippon Shinyaku; and affiliation with the division supported by endowments from Nippon Shinyaku, Nippon Boehringer Ingelheim, and Mochida Pharmaceutical, outside the submitted work. Dr Yaoita reports personal fees from Bayer Yakuhin and Konica Minolta, outside the submitted work. Dr Minatsuki reports a grant from Fukuda Foundation for Medical Technology, outside the submitted work. Dr Todaka reports a grant from Mochida Pharmaceutical; and personal fee from Bayer Yakuhin, outside the submitted work. Dr Fukuda reports grants from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical; and personal fees from Bayer Yakuhin, Daiichi Sankyo, Nippon Boehringer Ingelheim, Pfizer, Eisai, Janssen Pharmaceutical, Nippon Shinyaku, GlaxoSmithKline, and Mochida Pharmaceutical, outside the submitted work. Dr Tsutsui reports grants from Mitsubishi Tanabe Pharma, IQVIA Services Japan, MEDINET, Medical Innovation Kyushu, Kowa, Daiichi Sankyo, Johnson & Johnson, NEC, and Nippon Boehringer Ingelheim; personal fees from Novartis Pharma, Ono Pharmaceutical, Nippon Boehringer Ingelheim, Bayer Yakuhin, Kowa, Teijin Pharma, Mitsubishi Tanabe Pharma, Pfizer Japan, Daiichi Sankyo, Novartis Pharma, Janssen Pharmaceutical, Pfizer Japan, Bayer Yakuhin, Otsuka Pharmaceutical, AstraZeneca, and Nippon Rinsho; and is Chairman of Japan Heart Failure Society, outside the submitted work. Dr Abe reports a grant from Konica Minolta and Daiichi Sankyo, outside the submitted work. Drs Watanabe, Yasuda, Kobayakawa, Adachi, and Tatsumi report no conflicts of interest.

Figures

Figure.
Figure.
Summary of primary findings in the KABUKI trial. A, Primary end point: week 48 to baseline ratio of pulmonary vascular resistance (PVR). Geometric mean ratio of PVR (week 48 to baseline) was 0.93 (95% CI, 0.86–1.01) in the edoxaban group and 1.01 (95% CI, 0.93–1.10) in the warfarin group, resulting in a treatment effect (ratio of geometric means for edoxaban compared with warfarin of 0.920 [95% CI, 0.820–1.032]; P<0.0001 for noninferiority). B, Exploratory outcome: change in PVR at week 48 from baseline. The least squares (LS) mean difference between the edoxaban group and warfarin group (treatment effect) of change in PVR at week 48 from baseline was −0.155 Wood Units (95% CI, −0.416 to 0.107; P=0.242). C, Secondary end point: changes in 6-minute walk distance at week 48 from baseline. The LS mean difference between the edoxaban group and warfarin group (treatment effect) of change in 6-minute walk distance at week 48 was 5.6 m (95% CI, –16.4 to 27.6; P=0.612). D, Secondary end point: changes in NT-proBNP level at prespecified visits from baseline. The LS mean difference between the edoxaban group and warfarin group (treatment effect) of change in NT-proBNP level at week 48 from baseline was 0.834 pg/mL (95% CI, 0.672–1.036; P=0.099). E, Exploratory outcome: changes in mean pulmonary artery pressure at week 48 from baseline. The LS mean difference between the edoxaban group and the warfarin group (treatment effect) of change in pulmonary artery pressure at week 48 from baseline was 0.2 mm Hg (95% CI, –2.0 to 2.3; P=0.888). F, Exploratory outcome: changes in d-dimer level at prespecified visits from baseline. The LS mean difference between the edoxaban group and the warfarin group (treatment effect) of change in d-dimer level at week 48 from baseline was 0.07 µg/mL (95% CI, –0.07 to 0.21; P=0.337). NT-proBNP indicates N-terminal pro–B-type natriuretic peptide.
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References

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