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Clinical outcomes according to dose reduction criteria of apixaban in Japanese elderly patients with atrial fibrillation: J-ELD AF Registry subanalysis

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Abstract

Dose reduction of apixaban is applied in atrial fibrillation (AF) patients fulfilling ≥ 2 of the following criteria: (1) age ≥ 80 years, (2) body weight ≤ 60 kg and (3) serum creatinine ≥ 1.5 mg/dL. However, the clinical significance of each criterion remains unclear. The J-ELD AF Registry is a prospective observational study of elderly (≥ 75 years) Japanese AF patients receiving on-label dose of apixaban. In patients receiving the standard dose (5 mg bid, n = 1243), the incidence rates (% per patient-year) of stroke or systemic embolism in those fulfilling none [n = 516] or one of the above criteria (1) [n = 328], (2) [n = 378] and (3) [n = 21] were 1.24, 2.32, 1.41 and 4.93 (log-rank P = 0.422), respectively, and those of bleeding requiring hospitalization were 1.03, 0.99, 1.98 and 4.93 (P = 0.318), respectively. In patients receiving a reduced dose (2.5 mg bid, n = 1,515), the incidences of stroke or systemic embolism in those fulfilling (1)/(2) [n = 1,331], (1)/(3) [n = 65], (2)/(3) [n = 23] and all three criteria [n = 96] were 1.38, 1.64, 4.67 and 3.51 (P = 0.295), respectively, and those of bleeding requiring hospitalization were 2.04, 1.64, 0.00 and 4.71 (P = 0.318), respectively. Univariate analysis demonstrated that the types or combinations of each criterion was not significantly associated with the incidence of thromboembolic or bleeding events. The types or combinations of the three apixaban dose reduction criteria did not have significant impact on effectiveness and safety in Japanese elderly AF patients receiving on-label dose of apixaban, although the impact of the creatinine criterion remains uncertain due to the few number of the patients.

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Acknowledgements

We would like to thank the J-ELD AF investigators for their support in patient registration and data collection: Caress Sapporo Hokko Memorial Clinic (Ichiro SAKUMA), Tosei General Hospital (Masayoshi AJIOKA), National Cerebral and Cardiovascular Center (Kengo KUSANO), Tokyo Dental College Ichikawa General Hospital (Takahiro OHKI), Kyoto University Graduate School of Medicine (Takeshi KIMURA), Kyoto Medical Center (Masaharu AKAO), Yamamashi Kousei Hospital (Tetsuya ASAKAWA), Tachikawa General Hospital (Masaaki OKABE), Uwajima City Hospital (Akiyoshi OGIMOTO), Toho University Faculty of Medicine (Takanori IKEDA), Nara Medical University Hospital (Taku NISHIDA), Kameda Medical Center (Akira MIZUKAMI), Tabuchi Cardiovascular Internal Medicine Clinic (Toshifumi TABUCHI), The Cardiovascular Institute (Takeshi YAMASHITA), Honjo Daiichi Hospital (Yasushi SUZUKI), Kitasato University (Junya AKO), Keio University Hospital (Seiji TAKATSUKI), Kitaishikai Hospital (Takumi SUMIMOTO), Tokyo Women`s Medical University (Nobuhiwa HAGIWARA), Osaka General Medical Center (Takahisa YAMADA), Chikamori Hospital, Chikamori Health Care Group (Masahiko FUKATANI), Kanto Central Hospital (Nobuhiko ITO), Fukuda Memorial Hospital (Kohsuke NAKAJIMA), Japanese Red Cross Society Yamaguchi Hospital (Hiroyuki MICHISHIGE), National Hospital Organization Osaka National Hospital (Yukihiro KORETSUNE), Nakamura Memorial Hospital (Kenji KAMIYAMA), Ogori Daiichi General Hospital (Naoki SUGI), Yamato Municipal Hospital (Takaaki KUBO), Sendai City Hospital (Tetsuo YAGI), Hekinan Municipal Hospital (Atsushi SUGIURA), National Hospital Organization Tokyo Medical Center (Yukihiko MOMIYAMA), Oita Red Cross Hospital (Tetsu IWAO), Yao Municipal Hospital (Tetsuya WATANABE), Yuri Kumiai General Hospital (Tohru NAKANISHI), Fukushima Medical University Hospital (Yasuchika TAKEISHI), Okamisawa Clinic (Kunihiko KAMEDA), Dokkyo Medical University (Teruo INOUE), Saiseikai Kawaguchi General Hospital (Toshikazu FUNAZAKI), Nara Prefectural Seiwa Medical Center (Naofumi DOI), Osaka Police Hospital (Yoshiharu HIGUCHI), Tokyo Metropolitan Geriatric Hospital (Yusuke Tsuboko), Kitakami Saiseikai Hospital (Yoshihiro SATO), Machii Cardiovascular Internal Medicine Clinic (Kazuo MACHII), Tokyo Metropolitan Health and Medical Treatment Corporation Ebara Hospital (Yasunaga HIYOSHI), Ube-kohsan Central Hospital (Masahiko HARADA), Kitano Hospital, Tazuke Kofukai Medical Research Institute (Moriaki INOKO), Hirakata Kohsai Hospital (Hiroyuki TAKENAKA), Kobe City Medical Center General Hospital (Yutaka FURUKAWA), Kokura Memorial Hospital (Kenji ANDO), Tenri Hospital (Yoshihisa NAKAGAWA), Hyogo Prefectural Amagasaki General Medical Center (Kazuyasu YOSHITANI), Shimabara Hospital (Mamoru TAKAHASHI), Mitsubishi Kyoto Hospital (Shinji MIKI), Koto Memorial Hospital (Tomoyuki MURAKAMI), Sakurabashi Watanabe Hospital (Koichi INOUE), Japan Community Health Care Organization Hoshigaoka Medical Center (Yuzuru TAKANO), Nippon Medical School (Wataru SHIMIZU), Daido Hospital (Tomoharu ARAKAWA), Tokushima University Graduate School (Masataka SATA), Mashiko Hospital (Shogo SHIMIZU), Hirosaki Stroke and Rehabilitation Center (Joji HAGII), Kashiwaba Neurosurgical Hospital (Tetsuyuki YOSHIMOTO), Sendai Cardiovascular Center (Shinya Fujii), Faculty of Medicine, Oita University (Naohiko TAKAHASHI), Tsuji Clinic (Hikari TSUJI), Yamato Kashihara Hospital (Tamio NAKAJIMA), Omori Internal Medicine and Cardiology Clinic (Masayuki WATANABE), Fujita Health University School of Medicine (Eiichi WATANABE), Oita Medical Center (Masaya ARIKAWA), Ota Clinic (Akira OTA), Ozaki Cardiology Clinic (Masaharu OZAKI), NHO Kumamoto Saishusou Hospital (Ikuo MISUMI), Kansai Rosai Hospital (Masaaki UEMATSU), Hatayama Clinic (Toru HATAYAMA), SATO Internal Medicine Pediatrics clinic (Atsushi SATO), Narita Medical Clinic (Hidetoshi NARITA), Toyamori Internal Medicine pediatrics clinic (Hiroshi TOYAMORI), St.Mary's Heart Clinic (Kazuhiro YOSHIDA), Furukawa Medical Clinic (Kayoko FURUKAWA), Iwate Medical University (Takashi KOMATSU), Yamaguchi University Graduate School of Medicine (Akihiko SHIMIZU), Shizuoka City Shizuoka Hospital (Tomoya ONODERA), Igarashi Clinic, Cardiology and Internal Medicine (Morio IGARASHI), Fujino Circulation Clinic (Takao FUJINO), Japan Community Health Care Organization Osaka Hospital (Shinji HASEGAWA), Suzuki Internal Medicine Clinic (Tomomi SUZUKI), Odawara municipal hospital (Masaru YUGE), Inoue Cardiology and Internal Medicine Clinic (Takeshi INOUE), Okidate Heart Clinic (Takeshi KUDO), Saien Heart Medical Clinic (Toshihiko KOEDA), Japanese Red Cross Society Fukushima Hospital (Takayuki OHWADA), Sumi Cardiovascular Clinic (Hirokuni SUMI), Takei Clinic (Jinko YAMABE), Iwate Prefectural Kamaishi Hospital (Mahito OZAWA), Medical Corporation Association Koukeikai Sugiura Clinic (Toshiyuki SUGIURA), Hirosaki University Graduate School of Medicine (Ken OKUMURA and Hirofumi TOMITA), Kondo Internal Medicine Clinic (Kazuhiko KONDO), Chiba Surgical Hospital (Yasuhide MORIKAWA), Tokyo Women's Medical University, Yachiyo Medical Center (Shoji HARUTA), ISHIDA Medical Clinic (Shuji ISHIDA), Kindai University Nara Hospital (Manabu SHIROTANI), Nara Prefecture General Medical Center (Fumitaka INOUE), Kumamoto City Hospital (Koji SATO), National Hospital Organization Kumamoto Medical Center (Kazuteru FUJIMOTO), Tohoku Medical and Pharmaceutical University Hospital (Yoshiaki KATAHIRA), Awa Regional Medical Center (Akira MIZUKAMI), Horii Clinic (Norihiko MATSUMURA), JCHO Kumamoto General Hospital (Shinji TAYAMA), Japanese Red Cross Kumamoto Hospital (Ryusuke TSUNODA), Shiga General Hospital Cardiology division (Shigeru IKEGUCHI).

Funding

This study was conducted by the Cardiovascular Institute Academic Research Organization (CVI ARO), Tokyo, Japan, subsidized and funded by pharmaceutical and medical device companies. Bristol-Myers Squibb K.K. provided monetary support for this study. This study was partially supported by the Practical Research Project for Life-Style related Diseases including Cardiovascular Diseases and Diabetes Mellitus from Japan Agency for Medical Research and Development, AMED (JP19ek0210082h0003). The present study was funded by Bristol Myers Squibb, which had no role in the design, performing and reporting of the study.

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Authors and Affiliations

  1. Department of Cardiology, National Hospital Organization Kyoto Medical Center, 1-1 Fukakusa Mukaihata-cho, Fushimi-ku, Kyoto, Kyoto, 612-8555, Japan

    Masaharu Akao

  2. Department of Cardiovascular Medicine, The Cardiovascular Institute, Tokyo, Japan

    Takeshi Yamashita & Shinya Suzuki

  3. Division of Cardiology, Saiseikai Kumamoto Hospital, Kumamoto, Japan

    Ken Okumura

Authors
  1. Masaharu Akao
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  2. Takeshi Yamashita
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  3. Shinya Suzuki
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  4. Ken Okumura
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Consortia

J-ELD AF Investigators

  • Ichiro Sakuma
  • , Masayoshi Ajioka
  • , Kengo Kusano
  • , Takahiro Ohki
  • , Takeshi Kimura
  • , Masaharu Akao
  • , Tetsuya Asakawa
  • , Masaaki Okabe
  • , Akiyoshi Ogimoto
  • , Takanori Ikeda
  • , Taku Nishida
  • , Akira Mizukami
  • , Toshifumi Tabuchi
  • , Takeshi Yamashita
  • , Yasushi Suzuki
  • , Junya Ako
  • , Seiji Takatsuki
  • , Takumi Sumimoto
  • , Nobuhiwa Hagiwara
  • , Takahisa Yamada
  • , Masahiko Fukatani
  • , Nobuhiko Ito
  • , Kohsuke Nakajima
  • , Hiroyuki Michishige
  • , Yukihiro Koretsune
  • , Kenji Kamiyama
  • , Naoki Sugi
  • , Takaaki Kubo
  • , Tetsuo Yagi
  • , Atsushi Sugiura
  • , Yukihiko Momiyama
  • , Tetsu Iwao
  • , Tetsuya Watanabe
  • , Tohru Nakanishi
  • , Yasuchika Takeishi
  • , Kunihiko Kameda
  • , Teruo Inoue
  • , Toshikazu Funazaki
  • , Naofumi Doi
  • , Yoshiharu Higuchi
  • , Yusuke Tsuboko
  • , Yoshihiro Sato
  • , Kazuo Machii
  • , Yasunaga Hiyoshi
  • , Masahiko Harada
  • , Moriaki Inoko
  • , Hiroyuki Takenaka
  • , Yutaka Furukawa
  • , Kenji Ando
  • , Yoshihisa Nakagawa
  • , Kazuyasu Yoshitani
  • , Mamoru Takahashi
  • , Shinji Miki
  • , Tomoyuki Murakami
  • , Koichi Inoue
  • , Yuzuru Takano
  • , Wataru Shimizu
  • , Tomoharu Arakawa
  • , Masataka Sata
  • , Shogo Shimizu
  • , Joji Hagii
  • , Tetsuyuki Yoshimoto
  • , Shinya Fujii
  • , Naohiko Takahashi
  • , Hikari Tsuji
  • , Tamio Nakajima
  • , Masayuki Watanabe
  • , Eiichi Watanabe
  • , Masaya Arikawa
  • , Akira Ota
  • , Masaharu Ozaki
  • , Ikuo Misumi
  • , Masaaki Uematsu
  • , Toru Hatayama
  • , Atsushi Sato
  • , Hidetoshi Narita
  • , Hiroshi Toyamori
  • , Kazuhiro Yoshida
  • , Kayoko Furukawa
  • , Takashi Komatsu
  • , Akihiko Shimizu
  • , Tomoya Onodera
  • , Morio Igarashi
  • , Takao Fujino
  • , Shinji Hasegawa
  • , Tomomi Suzuki
  • , Masaru Yuge
  • , Takeshi Inoue
  • , Takeshi Kudo
  • , Toshihiko Koeda
  • , Takayuki Ohwada
  • , Hirokuni Sumi
  • , Jinko Yamabe
  • , Mahito Ozawa
  • , Toshiyuki Sugiura
  • , Ken Okumura
  • , Hirofumi Tomita
  • , Kazuhiko Kondo
  • , Yasuhide Morikawa
  • , Shoji Haruta
  • , Shuji Ishida
  • , Manabu Shirotani
  • , Fumitaka Inoue
  • , Koji Sato
  • , Kazuteru Fujimoto
  • , Yoshiaki Katahira
  • , Akira Mizukami
  • , Norihiko Matsumura
  • , Shinji Tayama
  • , Ryusuke Tsunoda
  •  & Shigeru Ikeguchi

Corresponding author

Correspondence to Masaharu Akao.

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Conflict of interest

MA received lecture fees from Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare and Daiichi-Sankyo. TY received lecture fees from Bristol Myers Squibb, Daiichi-Sankyo, Bayer, Pfizer, Ono Pharmaceutical and Toa Eiyo and research funding from Bayer and Daiichi Sankyo. SS received research funding from Daiichi-Sankyo and Mitsubishi-Tanabe. KO received lecture fees from Daiichi-Sankyo, Boehringer Ingelheim and Johnson and Johnson.

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J-ELD AF investigators members are listed in the Acknowledgement section.

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Akao, M., Yamashita, T., Suzuki, S. et al. Clinical outcomes according to dose reduction criteria of apixaban in Japanese elderly patients with atrial fibrillation: J-ELD AF Registry subanalysis. Heart Vessels 36, 1035–1046 (2021). https://doi.org/10.1007/s00380-021-01777-3

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