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Effects of Tolvaptan on Volume Overload in Japanese Patients with Heart Failure: Results of a Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study

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Abstract

Purpose

Tolvaptan may reduce the signs of volume overload in heart failure (HF) patients who experience volume overload despite using conventional diuretics. In this study, we evaluated the dose-response effects of tolvaptan on weight loss, urine volume and electrolyte excretion in furosemide-treated Japanese HF patients exhibiting volume overload.

Methods

In the study, 117 HF patients with volume overload on stable doses of furosemide (≥40 mg/day) were treated with tolvaptan (15, 30 or 45 mg) or placebo once-daily for 7 days.

Results

The decrease in body weight from baseline to the day after the final dose with 15, 30 or 45 mg tolvaptan (–1.62 ± 1.55, –1.35 ± 1.54 and –1.85 ± 1.10 kg, respectively), was significantly greater compared with that in the placebo group (–0.53 ± 0.96 kg) (p < 0.05). However, the decrease in body weight with tolvaptan was not significantly dose-dependent. Signs of volume overload improved at all doses of tolvaptan. Tolvaptan elicited a dose-dependent increase in urine volume and a decrease in urine osmolality, but did not affect urinary sodium or potassium excretion. Adverse reactions associated with diuresis were most frequently observed at the higher doses of tolvaptan.

Conclusions

Once-daily tolvaptan (15, 30 or 45 mg) was effective and tolerable as an add-on treatment to furosemide therapy in Japanese HF patients with volume overload.

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Disclosures

None of the authors have any conflicts of interest associated with this study.

Author information

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine and Clinical Science, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan

    Masunori Matsuzaki

  2. Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan

    Masatsugu Hori

  3. Department of Cardio-Angiology, Kitasato University School of Medicine, 1-15-1 Kitasato, Minamiku, Sagamihara, Kanagawa, 252-0373, Japan

    Tohru Izumi

  4. Imizu City Hospital, Toyama, Japan

    Hidetsugu Asanoi

  5. Department of Cardiovascular and Respiratory Medicine, Shiga University of Medical Science, Shiga, Japan

    Takayoshi Tsutamoto

Authors
  1. Masunori Matsuzaki
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  2. Masatsugu Hori
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  3. Tohru Izumi
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  4. Hidetsugu Asanoi
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  5. Takayoshi Tsutamoto
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Consortia

for the Tolvaptan Investigators

Corresponding author

Correspondence to Tohru Izumi.

Appendix: Participating investigators and institutions

Appendix: Participating investigators and institutions

The following investigators and institutions participated in this trial: Akihiro Azuma, University Hospital, Kyoto Prefectural University of Medicine, Kyoto; Yoshinori Doi, Kochi Medical School Hospital, Nankoku, Kochi; Kenji Fujii, Sakurabashi Watanabe Hospital, Osaka; Kazuteru Fujimoto, National Hospital Organization Kumamoto Medical Center, Kumamoto; Jun Fuse, National Hospital Organization Tokyo Medical Center, Meguro, Tokyo; Hiroyuki Hanada, Hirosaki University School of Medicine & Hospital, Hirosaki, Aomori; Michiaki Hiroe, National Center for Global Health and Medicine, Shinjuku, Tokyo; Hitoshi Hishida, Fujita Health University, Toyoake, Aichi; Hiroaki Hosokawa, National Hospital Organization Toyohashi Medical Center, Toyohashi, Aichi; Takayuki Inomata, Kitasato University Hospital, Sagamihara, Kanagawa; Ryoji Ishiki, Toyota Memorial Hospital, Toyota, Aichi; Hideo Izawa, Nagoya University Hospital, Nagoya, Aichi; Toshio Kasai, National Hospital Organization Nagano National Hospital, Nagano; Shu Kasama, Cardiovascular Hospital of Central Japan, Seta-gun, Gunma; Shun-ichi Kobayashi, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Kanagawa; Masahiko Koda, Gifu Prefectural General Medical Center, Gifu; Sunao Kojima, Kumamoto University Hospital, Kumamoto; Kengo Matsumoto, National Hospital Organization Kure Medical Center, Kure, Hiroshima; Takahiro Matsumoto, National Hospital Organization Kyushu Medical Center, Fukuoka; Tatsuru Matsuoka, National Hospital Organization Kagoshima Medical Center, Kagoshima; Shinji Miki, Mitsubishi Kyoto Hospital, Kyoto; Kazuaki Mitsudo, Kurashiki Central Hospital, Kurashiki, Okayama; Toshiro Miura, Yamaguchi University Hospital, Ube, Yamaguchi; Shigeyuki Nishimura, Saitama Medical University Hospital, Iruma-gun, Saitama; Ryuji Nohara, Kitano Hospital, Osaka; Akira Nozaki, Kanto Central Hospital of the Mutual Aid Association of Public School Teachers, Setagaya, Tokyo; Hiroshi Ogawa, Tokuyama Central Hospital, Shunan, Yamaguchi; Yoshihiko Sakai, Dokkyo Medical University Koshigaya Hospital, Koshigoe, Saitama; Mamoru Sato, Iwate Medical University Hospital, Morioka, Iwate; Ikuo Segawa, Iwate Medical University Hospital, Morioka, Iwate; Yoshihiko Seino, Nippon Medical School Hospital, Bunkyo, Tokyo; Junya Shite, Kobe University Hospital, Kobe, Hyogo; Jun-ichi Suzuki, Tokyo Medical and Dental University, Bunkyo, Tokyo; Masahiro Suzuki, National Hospital Organization Saitama National Hospital, Wako, Saitama; Shuichi Taguchi, National Hospital Organization Mito Medical Center, Ibaraki; Yoshifumi Takada, Tokyo Medical University Hospital, Shinjuku, Tokyo; Keiji Tanaka, Nippon Medical School Hospital, Bunkyo, Tokyo; Masaru Tanaka, Osaka Red Cross Hospital, Osaka; Jun Tanouchi, Osaka Rosai Hospital, Sakai, Osaka; Chuwa Tei, Kagoshima University Medical And Dental Hospital, Kagoshima; Hitoshi Toda, Kagoshima City Hospital, Kagoshima; Kazufumi Tsuchihashi, Sapporo Medical University Hospital, Sapporo, Hokkaido; Hitoshi Yasumoto, Kokura Memorial Hospital, Kitakyushu, Fukuoka; Yoshio Yasumura, National Hospital Organization Osaka National Hospital, Osaka; Hiroyuki Yokoyama, National Hospital Organization Shizuoka Medical Center, Suntou gun, Shizuoka.

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Matsuzaki, M., Hori, M., Izumi, T. et al. Effects of Tolvaptan on Volume Overload in Japanese Patients with Heart Failure: Results of a Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study. Cardiovasc Drugs Ther 25 (Suppl 1), 19–31 (2011). https://doi.org/10.1007/s10557-011-6303-y

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