Circ J 2018; 82: 691 – 698 Supplementary File doi: 10.1253/circj.CJ-17-0442

Anemia Is Associated With Blunted Response to β-Blocker Therapy Using Carvedilol ― Insights From Japanese Chronic Heart Failure (J-CHF) Study ―

Yuji Nagatomo, MD; Tsutomu Yoshikawa, MD; Hiroshi Okamoto, MD; Akira Kitabatake, MD; Masatsugu Hori, MD on behalf of J-CHF Investigators

——— Supplementary File 1 ———

• Haruki Musha (Yokohama City Seibu Hospital) Appendix S1. The J-CHF Program Committees and Members • Toshiaki Ebina (Yokohama City University Yokohama Seibu Executive Committee Hospital) Masatsugu Hori, Satoshi Ogawa, Ryozo Nagai, Masanori Matsuzaki, • Ichiro Michishita (Yokohama Kyosai Hospital) Yasuo Ohashi, Hitonobu Tomoike, Hiroshi Okamoto. • Tetsuo Takahashi (Yokohama City Hospital) Steering Committee • Satoshi Umemura (Yokohama City University School of Medicine) Hiroyuki Tsutsui, Iwao Yamaguchi, Ryozo Nagai, Satoshi Ogawa, • Toyoji Nemoto (National Sagamihara Hospital) Tsutomu Yoshikawa, Nobuhisa Hagiwara, Michihiro Yoshimura, • Tohru Izumi (Kitasato University School of Medicine) Katsuo Kanmatsuse, Satoshi Umemura, Minoru Takekoshi, Yoshifusa • Hideo Himeno (Fujisawa City Hospital) Aizawa, Hisayoshi Fujiwara, Masatsugu Hori, Kunio Miyatake, • Teruhisa Tanabe (Tokai University School of Medicine) Junichi Yoshikawa, Mitsuhiro Yokoyama, Toru Kita, Masanori • Hiroyuki Daida (Juntendo University) Matsuzaki, Toru Ohe, Yoshinori Doi, Takao Higaki, Imaizumi • Mitsuaki Isobe (Tokyo Medical and Dental University) Tsutomu. • Koichiro Kinugawa (Tokyo University School of Medicine) Protocol Committee • Yoshihioko Seino (Nippon Medical University) Toru Izumi, Yasuo Ohashi, Akira Kitabatake, Hiroshi Okamoto, • Takahisa Uchiyama (Nihon University School of Medicine, Tsutomu Yamazaki. Nerima Hikarigaoka Hospital) Data Safety Monitoring Committee • Katsuo Kanmatsuse (Surugadai Nihon University Hospital) Saichi Hosoda, Yoshio Yazaki, Shigei Shinoyama. • Satoshi Saito (Nihon University School of Medicine, Itabashi Endpoint Classification Committee Hospital) Masatsugu Hori, Hiroshi Okamoto, Tsutomu Yoshikawa, Tsutomu • Naoki Matsuda (Tokyo Women’s Medical University) Yamazaki, Makoto Masuyama, Hiroyuki Tsutsui, Yasuo Ohashi. • Satoshi Ogawa (Keiyo University School of Medicine) Administration Office • Seibu Mochizuki (Tokyo Jikeikai University School of Medicine) Tsutomu Yamazaki. • Junichi Yamazaki (Toho University Medical School Omori Hospital) Monitoring Office • Kiyoshi Inoue (Tokyo Metropolitan Police Hospital) Yasuo Ohashi. • Takashi Ito (Tokyo Teishin Hospital) • Makoto Akaishi (Kitasato Institute Hospital) • Shin-ichi Momomura (Toranomon Hospital) Appendix S2. The J-CHF Trial Study Group: Total 237 Sites • Keiko Oikawa (Cardiovascular Institute Hospital) • Hiroyuki Tsutsui (Hokkaido University Hospital) • Toshiyuki Degawa (Sempos Tokyo Tkanawa Hospital) • Takayuki Hirabayashi (Sunagawa City Hospital) • Kazuya Kawai (Chikamori-kai Medical Corporation Chikamori • Takatoshi Nishimiya (Asahikawa Red Cross Hospital) Hospital) • Shigeru Takechi (Date Red Cross Hospital) • Keicho Miyamoto (Tobu Chiiki Hospital) • Hidetsugu Sakai (Kushiro Rosai Hospital) • Masatoshi Nagayama (Sakakibara Commemoration Hospital) • Kenjiro Kikuchi (Asahikawa Medical University) • Teruhiko Aoyagi (Japanese Red Cross Medical Center) • Koichi Kanda (Sapporo Kosei Hospital) • Kazumasa Harada (Tokyo Metropolitan Geriatric Hospital) • Noriyoshi Kato (Sapporo City Hospital) • Yuji Hashimoto (Kameda General Hospital) • Naoya Matsumura (Hakodate City Hospital) • Hirofumi Noike (Toho University Sakura Hospital) • Teisuke Anzai (Hakodate National Hospital) • Tatsuji Kanoh (Juntendo University Urayasu Hospital) • Kazufumi Tsuchihashi (Sapporo Medical University) • Issei Komuro (Graduate School of Medicine and School of • Tetsuro Shoji (Muroran City General Hospital) Medicine, Chiba University) • Mitsuhiro Nishimura (Caress Tenshi Hospital) • Yoshiki Uehara (Jikei University Kashiwa Hospital) • Takayuki Matsuki (New Nikko Muroran General Hospital) • Toshihiko Uchida (Koshigaya Hospital, Dokkyo University • Takashi Shogase (Caress Nikko Kinen Hospital) School of Medicine) • Hiroshi Asajima (Hakodate Central Hospital) • Masahiro Suzuki (Saitama National Hospital) • Yasukuni Shikano (JA Hokaido Obihiro Kosei Hospital) • Osami Kohmoto (Saitama Medical School Hospital) • Mitsuru Yui (Iwaki City General Iwaki Kyoritsu Hospital) • Fumitaka Ohsuzu (National Defense Medical College Hospital) • Katsuhiko Hiramori (Iwate Medical University) • Hitoshi Adachi (Gunma Prefectural Cardio-vascular Center) • Ken Okumura (Hirosaki University School of Medicine) • Masahiko Kurabayashi (Gunma University Graduate School of • Ken Kadowaki (Akita Seijinbyo Medical Center) Medicine) • Masahiro Yagi (Sendai Junkankibyo Center) • Takesatoru Fukuda (Saiseikai Maebashi Hospital) • Akira Hirosaka (Ohta General Hospital, Ohta Nishinouchi Hospital) • Toshiya Iwasaki (Cardiovascular Hospital of Central Japan) • Yoshiaki Katahira (Tohoku Kosei Nenkin Hospital) • Noboru Takekoshi (Kanazawa Medical University) • Yukio Maruyama (Fukushima Medical University) • Honin Kanaya (Ishikawa Prefectural Central Hospital) • Takaaki Kubo (Taketa Hospital) • Hiroshi Mabuchi (Kanazawa University Hospital) • Kazuhira Maehara (Shirakawa Kosei Hospital) • Yuji Okura (Niigata University Graduate School of Medical and • Kunio Shirato (Tohoku University Medical Hospital) Dental Sciences) • Youichi Takeyama (Showa University Fujigaoka Hospital) • Hiroshi Inoue (Toyama Medical and Pharmaceutical University)

Circulation Journal Vol.82, March 2018 • Yutaka Nitta (Toyama Red Cross Hospital) • Koichi Node (Saga Medical School Faculty of Medicine, Saga • Lee Jong-Dae (University of Fukui Hospital) University) • Makoto Morita (Fukui Hospital) • Takashi Honda (Saiseikai Kumamoto Hospital) • Katsushi Misawa (Fukui Junkanki Hospital) • Shuichi Oshima (Kumamoto Chuo Hospital) • Kiyoshi Yokoi (Gifu Prefectural Tajimi Hospital) • Naoki Makino (Kyushu University Hospital at Beppu) • Toshihiko Nagano (Nagara Medical Center) • Chuwa Tei (Kagoshima University) • Yoko Onozawa (Hamamatsu Rosai Hospital) • Hitoshi Toda (Kagoshima City Hospital) • Makoto Shimizu (Yaizu City Hospital) • Yoshisato Shibata (Miyazaki City County Hospital) • Hirofumi Kanda (Okazaki City Hospital) • Jitsuo Higaki (Ehime University Hospital) • Kazuhiko Nishigaki (Gifu University School of Medicine) • Takashi Kimura (Seiwa Memorial Hospital) • Shozo Ogawa (Tokai Central Hospital) • Tatsuya Sasaki (Osaka Kousei Nenkin Hospital) • Takashi Yada (Mie Prefectural General Medical Center) • Kazusuke Itoh (Nishi Sapporo National Hospital) • Takeshi Nakano (School of Medicine, Mie University) • Naomichi Miyazaki (Yokohama Senin Hoken Hospital) • Osamu Doi (Shizuoka General Hospital) • Shigeo Kakinoki (Otaru Kyokai Hospital) • Akinori Takizawa (Shizuoka Municipal Shizuoka Hospital) • Hisashi Matsuo (Keiwakai Ebetsu Hospital) • Hideharu Hayashi (Hamamatsu University School of Medicine) • Takefumi Ozaki (Chitose City Hospital) • Sigenori Ito (Toyohashi Heart Center) • Yoshiyuki Kijima (Higashiosaka City General Hospital) • Toshihiko Takamoto (Hokushin General Hospital) • Tomoharu Nakamura (Kushiro Ishikai Hospital) • Miyoshi Ohno (Japanese Red Cross Nagoya First Hospital) • Shinya Hiramitsu (Fujita Health University) • Toshikazu Sobue (Nagoya Ekisaikai Hospital) • Toshiaki Nakagawa (Cardio-vascular Center Hokkaido Ohno • Shinya Okamoto (Nabari City Hospital) Hospital) • Takashi Konishi (Tenri Hospital) • Masaharu Machida (Tomakomai General Hospital) • Ryuji Nohara (Kitano Hospital) • Tetsuro Kohya (Sapporo Medical Center NTT EC) • Kazuhisa Kodama (Osaka Police Hospital) • Yasuo Hayashi (Harasanshin Hospital) • Kazuo Haze (Osaka City General Hospital) • Yoji Hirakawa (Oita Prefectural Hospital) • Masatake Fukunami (Osaka General Medical Center) • Masakazu Kohno (Kagawa University Hospital Internal Medicine 2) • Kunihiko Hirose (Otsu Red Cross Hospital) • Nobuo Fukuda (Zentsuji National Hospital) • Masaaki Uematsu (Kansai Rosai Hospital) • Takashi Oki (Higashi Tokushima National Hospital) • Kinji Ishikawa (Kindai University School of Medicine) • Jun Fuse (National Hospital Organization Tokyo Medical Center) • Yoshiki Takatsu (Hyogo Prefectural Amagasaki Hospital) • Keiichi Nagami (Keiyu Hospital) • Kenichi Shiratori (Kobe City General Hospital) • Teishi Kajiya (Hyogo Brain and Heart Center) • Hitonobu Tomoike (National Cerebral and Cardiovascular Center) • Toshihiko Seo (Saiseikai Nakatsu Hospital) • Kenji Fujii (Sakurabashi Watanabe Hospital) • Kazuaki Yakabe (Nagasaki Municipal Medical Center) • Kojiro Awano (Miki City Hospital) • Toshihiko Yamasa (Sasebo City General Hospital) • Yoshiyuki Nagai (Rinku General Medical Center) • Shiro Hata (National Hospital Organization Ureshino Medical • Tetsuya Doi (Ijinkai Takeda General Hospital) Center) • Takeshi Aoyama (Kansai Denryoku Hospital) • Masami Fukahori (Nagasakiken Goto Central Hospital) • Mitsuo Matsuda (Kishiwada City Hospital) • Yoshito Tanioka (Omura Municipal Hospital) • Takeshi Kimura (Kyoto University Hospital ) • Nobuyuki Yamada (Fukuyama City Hospital) • Mitsuhiro Yokoyama (Kobe University Graduate School of • Seiichiro Usuki (Kobe Rosai Hospital) Medicine ) • Yoshiki Kusama (Nippon Medical School Tama Nagayama • Hiroyuki Yamagishi (Osaka City University Hospital) Hospital) • Masatsugu Hori (Osaka University Hospital) • Kimihiko Hoshino (Nippon Medical School Second Hospital) • Akira Ezumi (Osaka Railway Hospital) • Ichiro Yoshida (Hokuto Hospital) • Yoshihiko Saito (Nara University of Medical Science Hospital) • Eiichiro Imamura (Ogasawara Clinic, Sapporo Hospital) • Mitsumasa Ohyanagi (The Hospital of Hyogo College of Medicine) • Keigo Dote (Asa City Hospital) • Kiyoshi Yoshida (Kawasaki Medical School Hospital) • Mitsunori Okamoto (Hiroshima Prefectural Hospital) • Teruo Shiraki (Iwakuni Clinical Center) • Shuji Tsujiyama (Kure Kyosai Hospital) • Yuhji Furutani (Kanmon Medical Center) • Takayuki Ito (Aichi Medical University) • Masao Yoshizumi (Hiroshima University, The Graduate School of • Atsushi Nozawa (Wakkanai City Hospital) Biomedical Sciences) • Katsuhiko Sato (Hokko Memorial Hospital) • Yasuhiko Hayashi (Akanekai Tsuchiya General Hospital) • Hideyuki Takano (Iwamizawa Rosai Hospital) • Seiichi Haruta (Fukuyama Cardiovascular Hospital) • Isao Sato (Bibai Rosai Hospital) • Tohru Ohe (Okayama University, Graduate School of Medicine) • Yutaka Yamada (Asahikawa City Hospital) • Shunichi Kaseda (Hiroshima Red Cross Hospital & Atomic-bomb • Akihiko Nozawa (Hokkaido Prefectural Hospital Kitami) Survivors Hospital) • Yoshitoki Takagawa (Otaru Daini Municipal Hospital) • Shiro Ono (Saiseikai Yamaguchi General Hospital) • Masaaki Nanba (Sapporo Railway Hospital) • Masunori Matsuzaki (Yamaguchi University Hospital) • Naoko Kobayashi (Gorinbashi Internal Medicine Hospital) • Kazuhide Ogino (Tottori University Faculty of Medicine) • Tadasu Iwasaki (Senju Hospital) • Eiji Hyakuna (Saiseikai Simonoseki General Hospital) • Yasuro Nakata (Shizuoka Hospital, Juntendo University) • Kouji Sada (Shakaihoken Shimonoseki Kosei Hospital) • Tsuneo Fujiwara (Sankokai Miyazaki Hospital) • Yoshinori Doi (Kochi Medical School) • Daisuke Hotta (Sapporo Shakai Hoken Hospital) • Takashi Furuno (Hata Prefectural Hospital) • Hideo Nishikawa (Mie Heart Center) • Susumu Nakagawa (Saiseikai Central Hospital) • Takeo Naito (Showa Hospital Saibikai) • Yukio Kazatani (Ehime Prefectural Central Hospital) • Koji Hasegawa (National Hospital Organization Kyoto Medical • Takumi Sumimoto (Kitaishikai Hospital) Center) • Shoichi Senda (Kagawa University Hospital, Internal Medicine) • Junichi Yoshikawa (Osaka Hospital of Japan Seafarers relief • Toru Kubota (Kyushu University Hospital) Association) • Shinichi Ando (Saiseikai Futsukaichi Hospital) • Takeshi Motomiya (Omori Red Cross Hospital) • Shinji Sato (Kyushu Medical Center) • Masatoshi Kawana (Aoyama Hospital Tokyo Women’s Medical • Masanori Okabe (Saiseikai Fukuoka General Hospital) University) • Hideo Yamamoto (Kyushu Kousei Nenkin Hospital) • Hiromi Obata (Obihiro National Hospital) • Yoshitoshi Urabe (Kitakyushu Municipal Medical Center) • Tomohiko Shigemasa (Atami Hospital, International University of • Tsutomu Imaizumi (Kurume University) Health and Welfare) • Katsusuke Yano (Nagasaki University Graduate School of • Michiro Ishikawa (Toho University Ohashi Medical Center) Biomedical Sciences) • Shohei Sawada (Uji Hospital) • Shigeru Kohno (Nagasaki University Hospital Medicine and • Koichiro Sueyoshi (Shizuoka Municipal Shimizu Hospital) Dentistry) • Yasushi Suzuki (Honjo daiichi Hospital) • Shin Suzuki (Nagasaki Municipal Hospital) • Junichi Sanada (Kagoshima Prefectural Oshima Hospital) • Yoshihiro Iwasaki (Nagasaki Kouseikai Hospital) • Shinsuke Tsuji (Saga Social Insurance Hospital)

Circulation Journal Vol.82, March 2018 • Shigeru Nakamura (Kyoto-Katsura Hospital) • Yuji Hirokane (Saihaku Hospital) • Yoshio Kawase (Izumi Municipal Hospital) • Junichi Konishi (Kyoritsu General Hospital) • Takashi Takenaka (National Hospital Organization Hokkaido • Kiyoshi Doyama (Simada Municipal Hospital) Cancer Center) • Michio Takamatsu (Saku Central Hospital) • Kenji Obata (Hitoyoshi General Hospital) • Yoshinobu Okada (Niigata Cancer Center Hospital) • Akihiro Yazaki (Haibara General Hospital) • Masaya Miyagawa (Midorigaoka Hospital) • Yoshihiro Chimori (Hyogo Prefectural Nishinomiya Hospital)

Figure S1. Time course of estimated glomerular filtration rate (eGFR) in the [N] and [A] groups over 56 weeks. eGFR was signifi- cantly higher in [N] compared with [A] throughout the study period. Although eGFR showed no significant changes in [N] group during 56 weeks, it significantly decreased in [A]. *P<0.05, **P<0.01 compared with baseline value. [A], anemia group; [N], non- anemia group.

Figure S2. Time course of change in LVEF (A) and BNP (B) in groups divided by presence of CKD. LVEF increased in both non- CKD and CKD groups. There was no significant difference in the time course of the change in LVEF between the 2 groups (A). At baseline BNP was significantly higher in the CKD group compared with the non-CKD group. This difference persisted throughout the dose maintenance period (B). BNP, B-type natriuretic peptide; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; LVEF, left ventricular ejection fraction.

Circulation Journal Vol.82, March 2018 Figure S3. Kaplan-Meier curves of pri- mary endpoint in groups divided by presence or absence of chronic kidney disease (CKD). The CKD group had a higher rate of composite endpoint of death and hospitalization for cardiovas- cular causes including HF compared with the non-CKD group.

Circulation Journal Vol.82, March 2018