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

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