Clinical Outcomes of Off-Label Dosing of Direct Oral Anticoagulant Therapy Among Japanese Patients With Atrial Fibrillation Identified From the SAKURA AF Registry

被引：66

作者：

Murata, Nobuhiro ^{[1
]}

Okumura, Yasuo ^{[1
]}

Yokoyama, Katsuaki ^{[2
]}

Matsumoto, Naoya ^{[2
]}

Tachibana, Eizo ^{[3
]}

Kuronuma, Keiichiro ^{[3
]}

Oiwa, Koji ^{[4
]}

Matsumoto, Michiaki ^{[4
]}

Kojima, Toshiaki ^{[5
]}

Hanada, Shoji ^{[6
]}

Nomoto, Kazumiki ^{[7
]}

Arima, Ken ^{[8
]}

Takahashi, Fumiyuki ^{[9
]}

Kotani, Tomobumi ^{[10
]}

Ikeya, Yukitoshi ^{[11
]}

Fukushima, Seiji ^{[12
]}

Itoh, Satoru ^{[13
]}

Kondo, Kunio ^{[14
]}

Chiku, Masaaki ^{[15
]}

Ohno, Yasumi ^{[16
]}

Onikura, Motoyuki ^{[17
]}

Hirayama, Atsushi ^{[1
]}

Hirayama, A. ^{[18
,19
]}

Okumura, Y. ^{[18
]}

Kunimoto, S. ^{[18
]}

Okumura, Y. ^{[18
]}

Kato, M. ^{[18
]}

Udagawa, S. ^{[19
]}

Hirayama, A. ^{[18
,19
]}

Okumura, Y. ^{[18
]}

Watanabe, I ^{[18
]}

Hiro, T. ^{[18
]}

Takayama, T. ^{[18
]}

Kunimoto, S. ^{[18
]}

Nakai, T. ^{[18
]}

Kato, M. ^{[18
]}

Yokoyama, K. ^{[2
]}

Ikeda, A. ^{[2
]}

Matsumoto, N. ^{[2
]}

Tachibana, E. ^{[3
]}

Kuronuma, K. ^{[3
]}

Oiwa, K. ^{[4
]}

Matsumoto, M. ^{[4
]}

Nishida, T. ^{[4
]}

Kojima, T. ^{[5
]}

Ichikawa, M. ^{[5
]}

Hanada, S. ^{[20
]}

Nomoto, K. ^{[7
]}

Tosaka, T. ^{[7
]}

Sonoda, K. ^{[7
]}

机构：

[1] Nihon Univ, Itabashi Hosp, Div Cardiol, Tokyo, Japan

[2] Nihon Univ Hosp, Dept Cardiol, Tokyo, Japan

[3] Kawaguchi Municipal Med Ctr, Saitama, Japan

[4] Yokohama Chuo Hosp, Yokohama, Kanagawa, Japan

[5] Sekishindo Hosp, Saitama, Japan

[6] TMG Asaka Med Ctr, Saitama, Japan

[7] Tokyo Rinkai Hosp, Tokyo, Japan

[8] Kasukabe Med Ctr, Saitama, Japan

[9] Yasuda Hosp, Tokyo, Japan

[10] Makita Gen Hosp, Tokyo, Japan

[11] Itabashi Med Assoc Hosp, Tokyo, Japan

[12] Ukima Cent Hosp, Tokyo, Japan

[13] Itou Cardiovasc Clin, Saitama, Japan

[14] Kondo Clin, Tokyo, Japan

[15] Keiai Clin, Tokyo, Japan

[16] Ohno Med Clin, Tokyo, Japan

[17] Onikura Clin, Chiba, Japan

[18] Nihon Univ, Div Cardiol, Dept Med, Sch Med, Tokyo, Japan

[19] Nihon Univ, Dept Math, Sch Med, Tokyo, Japan

[20] Asakadai Cent Gen Hosp, Asaka, Saitama, Japan

[21] Kasukabe Municipal Hosp, Kasukabe, Saitama, Japan

[22] Kobari Gen Clin, Noda, Chiba, Japan

[23] Chikuma Cent Hosp, Nagano, Japan

[24] Yamada Clin, Nishio, Aichi, Japan

[25] Higashi Saitama Gen Hosp, Satte, Saitama, Japan

[26] Zengyodanchi Ishikawa Clin, Yokohama, Kanagawa, Japan

[27] Tokutake Clin, Saitama, Japan

[28] Sugino Clin, Hiroshima, Japan

[29] Yokohama Sotetsu Bldg Clin, Yokohama, Kanagawa, Japan

[30] Suzuki Clin, Tokyo, Japan

[31] Fujita Clin, Tokyo, Japan

[32] Yumikura Clin, Tokyo, Japan

[33] Keiai Hosp, Fujimi, Saitama, Japan

[34] Sekimachi Med Clin, Tokyo, Japan

[35] Tokiwadai Surg Hosp, Tokyo, Japan

[36] Hikarigaoka Clin, Kashiwa, Chiba, Japan

[37] Osuga Clin, Hamamatsu, Shizuoka, Japan

[38] Nakai Clin, Tokyo, Japan

[39] Kurumatani Clin, Tokyo, Japan

[40] Horinaka Hosp, Satte, Saitama, Japan

[41] Nasu Red Cross Hosp, Otawara, Tochigi, Japan

[42] Sato Clin, Hiroshima, Japan

[43] Kofune Clin, Tokyo, Japan

[44] Ikebukuro Okubo Clin, Tokyo, Japan

[45] Minami Machida Hosp, Machida, Tokyo, Japan

[46] Ishii Clin, Izumisano, Osaka, Japan

[47] Akabane Cent Hosp, Tokyo, Japan

[48] Hirose Clin, Suzuka, Mie, Japan

[49] Sekimoto Mem Hosp, Kawagoe, Saitama, Japan

[50] Matsumura Clin, Hirakata, Osaka, Japan

来源：

CIRCULATION JOURNAL | 2019年 / 83卷 / 04期

关键词：

Atrial fibrillation; Direct oral anticoagulants; Off-label dose therapy; ISCHEMIC-STROKE; VS; WARFARIN; RISK; RIVAROXABAN; DABIGATRAN; APIXABAN; EDOXABAN; EFFICACY; SAFETY;

D O I：

10.1253/circj.CJ-18-0991

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Off-label dosing of direct oral anticoagulants (DOACs) is encountered clinically among patients with atrial fibrillation (AF), although data on the clinical outcomes of over-and under-dosing are lacking in Japan. Methods and Results: We examined the clinical outcomes of off-label DOAC dosing using the SAKURA AF Registry, a prospective multicenter registry in Japan. Among 3,237 enrollees, 1,676 under any of the 4 DOAC regimens were followed up for a median of 39.3 months: 746 (45.0%), appropriate standard-dose; 477 (28.7%), appropriate low-dose; 66 (4.0%), over-dose; and 369 (22.2%) under-dose. Compared with the standard-dose group, patients in the under-and over-dose groups were significantly older and had a higher stroke risk. After multivariate adjustment, stroke/systemic embolism (SE) and death events were equivalent between the standard-and under-dose groups, but major bleeding events tended to be lower in the under-dose group (hazard ratio [HR] 0.474, P=0.0739). Composite events (stroke/SE, major bleeding, or death) were higher in the over-dose than in the standard-dose group (HR 2.714, P=0.0081). Conclusions: Clinical outcomes were not worse for under-dose than for standard-dose users among patients with different backgrounds. Over-dose users, however, were at higher risk for all clinical events and required careful follow-up. Further studies are needed to clarify the safety and effectiveness of off-label DOAC dosing in Japan.

引用

页码：727 / +

页数：11

共 50 条

[31] Clinical outcomes of ablation versus non-ablation therapy for atrial fibrillation in Japan: analysis of pooled data from the AF Frontier Ablation Registry and SAKURA AF Registry
Kazuki Iso
Koichi Nagashima
Masaru Arai
Ryuta Watanabe
Katsuaki Yokoyama
Naoya Matsumoto
Takayuki Otsuka
Shinya Suzuki
Akio Hirata
Masato Murakami
Mitsuru Takami
Masaomi Kimura
Hidehira Fukaya
Shiro Nakahara
Takeshi Kato
Hiroshi Hayashi
Yu-ki Iwasaki
Wataru Shimizu
Ikutaro Nakajima
Tomoo Harada
Junjiroh Koyama
Ken Okumura
Michifumi Tokuda
Teiichi Yamane
Kojiro Tanimoto
Yukihiko Momiyama
Noriko Nonoguchi
Kyoko Soejima
Koichiro Ejima
Nobuhisa Hagiwara
Masahide Harada
Kazumasa Sonoda
Masaru Inoue
Koji Kumagai
Hidemori Hayashi
Yoshinao Yazaki
Kazuhiro Satomi
Yuji Watari
Yasuo Okumura
Heart and Vessels, 2021, 36 : 549 - 560
[32] Clinical characteristics and outcomes of japanese patients with atrial fibrillation and mitral regurgitation: the fushimi af registry
Doi, K.
Iguchi, M.
Ogawa, H.
Esato, M.
Wada, H.
Hasegawa, K.
Abe, M.
Akao, M.
EUROPEAN HEART JOURNAL, 2018, 39 : 207 - 207
[33] Patient Characteristics and Predictors of Off-Label versus Standard Dosing of Direct Oral Anticoagulants in Medicare Beneficiaries With Atrial Fibrillation
Briasoulis, Alexandros
Gao Yubo
Vaughan Sarrazin, Mary
CIRCULATION, 2018, 138
[34] Impact of Direct Oral Anticoagulant Concentration on Clinical Outcomes in Asian Patients with Atrial Fibrillation
Lin, Shin-Yi
Tang, Sung-Chun
Kuo, Ching-Hua
Ho, Li-Ting
Liu, Yen-Bin
Peng, Yu-Fong
Tsai, Li-Kai
Huang, Chih-Fen
Jeng, Jiann-Shing
CLINICAL PHARMACOLOGY & THERAPEUTICS, 2023, 114 (01) : 230 - 238
[35] Current Status, Time Trends and Outcomes of Combination Therapy With Oral Anticoagulant and Antiplatelet Drug in Patients With Atrial Fibrillation - The Fushimi AF Registry -
Masunaga, Nobutoyo
Abe, Mitsuru
Ogawa, Hisashi
Aono, Yuya
Ikeda, Syuhei
Doi, Kosuke
An, Yoshimori
Ishii, Mitsuru
Iguchi, Moritake
Esato, Masahiro
Tsuji, Hikari
Wada, Hiromichi
Hasegawa, Koji
Lip, Gregory Y. H.
Akao, Masaharu
CIRCULATION JOURNAL, 2018, 82 (12) : 2983 - +
[36] Off-Label Dosing of Non-Vitamin K Antagonist Oral Anticoagulants and Adverse Outcomes The ORBIT-AF II Registry
Steinberg, Benjamin A.
Shrader, Peter
Thomas, Laine
Ansell, Jack
Fonarow, Gregg C.
Gersh, Bernard J.
Kowey, Peter R.
Mahaffey, Kenneth W.
Naccarelli, Gerald
Reiffel, James
Singer, Daniel E.
Peterson, Eric D.
Piccini, Jonathan P.
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2016, 68 (24) : 2597 - 2604
[37] Real-World Prevalence of Direct Oral Anticoagulant Off-Label Doses in Atrial Fibrillation: An Epidemiological Meta-Analysis
Shen, Nan-Nan
Zhang, Chi
Hang, Ying
Li, Zheng
Kong, Ling-Cong
Wang, Na
Wang, Jia-Liang
Gu, Zhi-Chun
FRONTIERS IN PHARMACOLOGY, 2021, 12
[38] Clinical outcomes of Japanese atrial fibrillation patients with combined valvular heart disease: the Fushimi AF Registry
Doi, K.
Ishigami, K.
Aono, Y.
Ikeda, S.
Hamatani, Y.
Fujino, A.
An, Y.
Ishii, M.
Iguchi, M.
Ogawa, H.
Masunaga, N.
Wada, H.
Hasegawa, K.
Abe, M.
Akao, M.
EUROPEAN HEART JOURNAL, 2020, 41 : 528 - 528
[39] Clinical characteristics and outcomes in Japanese atrial fibrillation patients with valvular heart disease: the Fushimi AF registry
Doi, K.
Ishigami, K.
Aono, Y.
Ikeda, S.
An, Y.
Ishii, M.
Iguchi, M.
Masunaga, N.
Esato, M.
Wada, H.
Hasegawa, K.
Ogawa, H.
Abe, M.
Akao, M.
EUROPEAN HEART JOURNAL, 2019, 40 : 2375 - 2375
[40] Clinical characteristics and outcomes of atrial fibrillation patients taking direct oral anticoagulants in the real-world: The Fushimi AF Registry
Yamashita, Y.
Uozumi, R.
Esato, M.
Chun, Y.
Wada, H.
Hasegawa, K.
Ogawa, H.
Abe, M.
Morita, S.
Akao, M.
EUROPEAN HEART JOURNAL, 2016, 37 : 495 - 495

← 1 2 3 4 5 →