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 27 条

[1] Comparative Determinants of 4-Year Cardiovascular Event Rates in Stable Outpatients at Risk of or With Atherothrombosis [J].

Bhatt, Deepak L. ;

Eagle, Kim A. ;

Ohman, E. Magnus ;

Hirsch, Alan T. ;

Goto, Shinya ;

Mahoney, Elizabeth M. ;

Wilson, Peter W. F. ;

Alberts, Mark J. ;

D'Agostino, Ralph ;

Liau, Chiau-Suong ;

Mas, Jean-Louis ;

Roether, Joachim ;

Smith, Sidney C., Jr. ;

Salette, Genevieve ;

Contant, Charles F. ;

Massaro, Joseph M. ;

Steg, Ph. Gabriel .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2010, 304 (12) :1350-1357

[2] Dabigatran versus Warfarin in Patients with Atrial Fibrillation. [J].

Connolly, Stuart J. ;

Ezekowitz, Michael D. ;

Yusuf, Salim ;

Eikelboom, John ;

Oldgren, Jonas ;

Parekh, Amit ;

Pogue, Janice ;

Reilly, Paul A. ;

Themeles, Ellison ;

Varrone, Jeanne ;

Wang, Susan ;

Alings, Marco ;

Xavier, Denis ;

Zhu, Jun ;

Diaz, Rafael ;

Lewis, Basil S. ;

Darius, Harald ;

Diener, Hans-Christoph ;

Joyner, Campbell D. ;

Wallentin, Lars .

NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (12) :1139-1151

[3] Risk of Bleeding With 2 Doses of Dabigatran Compared With Warfarin in Older and Younger Patients With Atrial Fibrillation An Analysis of the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Trial [J].

Eikelboom, John W. ;

Wallentin, Lars ;

Connolly, Stuart J. ;

Ezekowitz, Mike ;

Healey, Jeff S. ;

Oldgren, Jonas ;

Yang, Sean ;

Alings, Marco ;

Kaatz, Scott ;

Hohnloser, Stefan H. ;

Diener, Hans-Christoph ;

Franzosi, Maria Grazia ;

Huber, Kurt ;

Reilly, Paul ;

Varrone, Jeanne ;

Yusuf, Salim .

CIRCULATION, 2011, 123 (21) :2363-U72

[4] Validation of clinical classification schemes for predicting stroke - Results from the national registry of Atrial Fibrillation [J].

Gage, BF ;

Waterman, AD ;

Shannon, W ;

Boechler, M ;

Rich, MW ;

Radford, MJ .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2001, 285 (22) :2864-2870

[5] Edoxaban versus Warfarin in Patients with Atrial Fibrillation [J].

Giugliano, Robert P. ;

Ruff, Christian T. ;

Braunwald, Eugene ;

Murphy, Sabina A. ;

Wiviott, Stephen D. ;

Halperin, Jonathan L. ;

Waldo, Albert L. ;

Ezekowitz, Michael D. ;

Weitz, Jeffrey I. ;

Spinar, Jindrich ;

Ruzyllo, Witold ;

Ruda, Mikhail ;

Koretsune, Yukihiro ;

Betcher, Joshua ;

Shi, Minggao ;

Grip, Laura T. ;

Patel, Shirali P. ;

Patel, Indravadan ;

Hanyok, James J. ;

Mercuri, Michele ;

Vogelmann, O. ;

Gonzalez, C. ;

Ahuad Guerrero, R. ;

Rodriguez, M. ;

Albisu, J. ;

Rosales, E. ;

Allall, O. ;

Reguero, M. ;

Alvarez, C. ;

Garcia, M. ;

Ameriso, S. ;

Ameriso, P. ;

Amuchastegui, M. ;

Caceres, M. ;

Beloscar, J. ;

Petrucci, J. ;

Berli, M. ;

Budassi, N. ;

Valle, M. ;

Bustamante Labarta, G. ;

Saravia, M. ;

Caccavo, A. ;

Fracaro, V. ;

Cartasegna, L. ;

Novas, V. ;

Caruso, O. ;

Saa Zarandon, R. ;

Colombo, H. ;

Morandini, M. ;

Cuello, J. .

NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (22) :2093-2104

[6] Efficacy and Safety of Apixaban Compared with Warfarin for Stroke Prevention in Patients with Atrial Fibrillation from East Asia: A Subanalysis of the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial [J].

Goto, Shinya ;

Zhu, Jun ;

Liu, Lisheng ;

Oh, Byung-Hee ;

Wojdyla, Daniel M. ;

Aylward, Philip ;

Bahit, M. Cecilia ;

Gersh, Bernard J. ;

Hanna, Michael ;

Horowitz, John ;

Lopes, Renato D. ;

Wallentin, Lars ;

Xavier, Denis ;

Alexander, John H. .

AMERICAN HEART JOURNAL, 2014, 168 (03) :303-309

[7] Apixaban versus Warfarin in Patients with Atrial Fibrillation [J].

Granger, Christopher B. ;

Alexander, John H. ;

McMurray, John J. V. ;

Lopes, Renato D. ;

Hylek, Elaine M. ;

Hanna, Michael ;

Al-Khalidi, Hussein R. ;

Ansell, Jack ;

Atar, Dan ;

Avezum, Alvaro ;

Cecilia Bahit, M. ;

Diaz, Rafael ;

Easton, J. Donald ;

Ezekowitz, Justin A. ;

Flaker, Greg ;

Garcia, David ;

Geraldes, Margarida ;

Gersh, Bernard J. ;

Golitsyn, Sergey ;

Goto, Shinya ;

Hermosillo, Antonio G. ;

Hohnloser, Stefan H. ;

Horowitz, John ;

Mohan, Puneet ;

Jansky, Petr ;

Lewis, Basil S. ;

Luis Lopez-Sendon, Jose ;

Pais, Prem ;

Parkhomenko, Alexander ;

Verheugt, Freek W. A. ;

Zhu, Jun ;

Wallentin, Lars .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (11) :981-992

[8] Predictive factors for bleeding during treatment with rivaroxaban and warfarin in Japanese patients with atrial fibrillation - Subgroup analysis of J-ROCKET AF [J].

Hori, Masatsugu ;

Matsumoto, Masayasu ;

Tanahashi, Norio ;

Momomura, Shin-ichi ;

Uchiyama, Shinichiro ;

Goto, Shinya ;

Izumi, Tohru ;

Koretsune, Yukihiro ;

Kajikawa, Mariko ;

Kato, Masaharu ;

Cavaliere, Mary ;

Iekushi, Kazuma ;

Yamanaka, Satoshi .

JOURNAL OF CARDIOLOGY, 2016, 68 (5-6) :523-528

[9] Dabigatran Versus Warfarin Effects on Ischemic and Hemorrhagic Strokes and Bleeding in Asians and Non-Asians With Atrial Fibrillation [J].

Hori, Masatsugu ;

Connolly, Stuart J. ;

Zhu, Jun ;

Liu, Li Sheng ;

Lau, Chu-Pak ;

Pais, Prem ;

Xavier, Denis ;

Kim, Sung Soon ;

Omar, Razali ;

Dans, Antonio L. ;

Tan, Ru San ;

Chen, Jyh-Hong ;

Tanomsup, Supachai ;

Watanabe, Mitsunori ;

Koyanagi, Masahide ;

Ezekowitz, Michael D. ;

Reilly, Paul A. ;

Wallentin, Lars ;

Yusuf, Salim .

STROKE, 2013, 44 (07) :1891-+

[10] Rivaroxaban vs. Warfarin in Japanese Patients With Atrial Fibrillation - The J-ROCKET AF Study [J].

Hori, Masatsugu ;

Matsumoto, Masayasu ;

Tanahashi, Norio ;

Momomura, Shin-ichi ;

Uchiyama, Shinichiro ;

Goto, Shinya ;

Izumi, Tohru ;

Koretsune, Yukihiro ;

Kajikawa, Mariko ;

Kato, Masaharu ;

Ueda, Hitoshi ;

Iwamoto, Kazuya ;

Tajiri, Masahiro .

CIRCULATION JOURNAL, 2012, 76 (09) :2104-2111

← 1 2 3 →