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Efficacy and safety of bisoprolol fumarate compared with carvedilol in Japanese patients with chronic heart failure: results of the randomized, controlled, double-blind, Multistep Administration of bisoprolol IN Chronic Heart Failure II (MAIN-CHF II) study

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An Erratum to this article was published on 19 June 2013

Abstract

Bisoprolol fumarate (bisoprolol) is a β-blocker widely used to treat chronic heart failure (CHF). However, few studies have compared its efficacy and safety with those of the widely used β-blocker carvedilol in Japanese patients with CHF. We designed a confirmatory trial of bisoprolol using carvedilol as a control drug; however, the trial was discontinued after an off-label use of bisoprolol was approved during the study. Bisoprolol and carvedilol were administered for 32 weeks in 31 and 28 patients, respectively. The mean maintenance doses of bisoprolol and carvedilol were 3.3 and 13.6 mg/day, respectively, and the mean durations of treatment were 188.2 and 172.9 days, respectively. Heart-rate changes were similar in both groups. The mean changes from baseline to Week 32 in left ventricular (LV) ejection fraction (EF) (bisoprolol vs carvedilol groups; 11.7 % ± 8.6 % vs 10.1 % ± 10.5 %), LV end-diastolic volume (−37.5 ± 48.7 vs −24.7 ± 29.4 ml), and LV end-systolic volume (−41.9 ± 43.0 vs −29.3 ± 25.9 ml) revealed a decrease in LV volume and an increase in LVEF in both groups. The cumulative event-free rate for a composite of cardiovascular death or admissions to hospital for worsening of CHF was 92.4 % and 94.7 % in the bisoprolol and carvedilol groups, respectively. Overall, 90.3 % and 85.7 % of patients were titrated up to the maintenance doses of bisoprolol and carvedilol, respectively. Bisoprolol, at half the dose used in other countries, is well tolerated and is as effective as carvedilol for treating Japanese patients with mild to moderate CHF.

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Acknowledgments

We wish to thank the members of the event evaluation committee and the cardiac function evaluation committee: Dr Hiroyuki Tsutsui, Dr Shin-ichi Momomura, Dr Issei Komuro, Dr Yoshihiko Saito, and Dr Tohru Masuyama. We also thank the staff at each study site for helping with patient enrollment and data collection. We thank Daiichi Sankyo Co., Ltd for providing carvedilol and Mitsubishi Tanabe Pharma Corporation for sponsoring this clinical trial. The trial sites were: Kihara Cardiovascular Clinic; Sapporo Kosei General Hospital; Hitachi General Hospital; Gunma Prefectural Cardiovascular Center; Kan-etsu Chuo Hospital; Cardiovascular Hospital of Central Japan; National Hospital Organization Saitama National Hospital; Shuwa General Hospital; Dokkyo Medical University Koshigaya Hospital; Saitama Medical Center Jichi Medical University; Saitama Medical University International Medical Center; The Jikei University Kashiwa Hospital; Toho University Omori Medical Center; Tokyo Medical University Hospital; Kanto Central Hospital of the Mutual Aid Association of Public School Teachers; Sempo Tokyo Takanawa Hospital; National Hospital Organization Tokyo Medical Center; National Hospital Organization Tokyo Hospital; Nihon University Nerima Hikarigaoka Hospital; Fussa Hospital; Kanagawa Cardiovascular and Respiratory Center; Kitasato University Hospital; Fukui General Clinic; NHO Matsumoto Medical Center Matsumoto Hospital; Ogaki Municipal Hospital; Japanese Red Cross Takayama Hospital; Nagoya Daini Red Cross Hospital; Nagoya City University Hospital; Social Insurance Chukyo Hospital; Fujita Health University Hospital; National Hospital Organization Toyohashi Medical Center; Mie University Hospital; Kusatsu General Hospital; Social Insurance Kyoto Hospital; Mitsubishi Kyoto Hospital; Kitano Hospital, The Tazuke Kofukai Medical Research Institute; Osaka General Medical Center; Osaka Police Hospital; Osaka Red Cross Hospital; Osaka Medical Center for Cancer and Cardiovascular Diseases; Osaka Rosai Hospital; Hokusetsu General Hospital; Takatsuki General Hospital; National Hospital Organization Osaka National Hospital; National Hospital Organization Kobe Medical Center; Hyogo College Of Medicine; Nara Medical University Hospital; Tenri Hospital; Japanese Red Cross Okayama Hospital; KKR Takamatsu Hospital; Kagawa Prefectural Central Hospital; Fukuokaken Saiseikai Futsukaichi Hospital; Fukuoka Red Cross Hospital; Medical Corporation Chiyukai Fukuoka Wajiro Hospital; Shinkoga Hospital; National Hospital Organization Ureshino Medical Center; Oita Oka Hospital; Seijinkai Ikeda Hospital; and Tenyoukai Chuo Clinic.

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Authors and Affiliations

  1. Osaka Medical Center for Cancer and Cardiovascular Diseases, 1-3-3 Nakamichi, Higashinari-ku, Osaka, 537-8511, Japan

    Masatsugu Hori

  2. Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan

    Ryozo Nagai

  3. Department of Cardio-Angiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan

    Tohru Izumi

  4. Department of Medicine and Clinical Science, Division of Cardiology, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8505, Japan

    Masunori Matsuzaki

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  1. Masatsugu Hori
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  2. Ryozo Nagai
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  3. Tohru Izumi
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  4. Masunori Matsuzaki
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Correspondence to Masatsugu Hori.

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Hori, M., Nagai, R., Izumi, T. et al. Efficacy and safety of bisoprolol fumarate compared with carvedilol in Japanese patients with chronic heart failure: results of the randomized, controlled, double-blind, Multistep Administration of bisoprolol IN Chronic Heart Failure II (MAIN-CHF II) study. Heart Vessels 29, 238–247 (2014). https://doi.org/10.1007/s00380-013-0340-3

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