Background More efficacious and/or safer decongestive therapy is clearly needed in acute heart failure (AHF) patients complicated by renal dysfunction. We tested the hypothesis that adding tolvaptan, an oral vasopressin-2 receptor antagonist, to conventional therapy with loop diuretics would be more effective treatment in this population. Methods and Results A multicenter, open-label, randomized control trial was performed, and 217 AHF patients with renal dysfunction (estimated glomerular filtration rate 15–60 mL • min−1 • 1.73 m−2) were randomized 1:1 to treatment with tolvaptan (n = 108) or conventional treatment (n = 109). The primary end point was 48-hour urine volume. The tolvaptan group showed more diuresis than the conventional treatment group (6464.4 vs 4999.2 mL; P < .001) despite significantly lower amounts of loop diuretic use (80 mg vs 120 mg; P < .001). Dyspnea relief was achieved significantly more frequently in the tolvaptan group at all time points within 48 hours except 6 hours after enrollment. The rate of worsening of renal function (≥0.3 mg/dL increase from baseline) was similar between the tolvaptan and conventional treatment groups (24.1% vs 27.8%, respectively; P = .642). Conclusions Adding tolvaptan to conventional treatment achieved more diuresis and relieved dyspnea symptoms in AHF patients with renal dysfunction. Clinical Trial Registration URL: http://www.umin.ac.jp/ctr/index/htm/ Unique identifier: UMIN000007109
Bibliographical noteFunding Information:
Funding/Support: The AQUAMARINE study was funded by Japan Heart Foundation Multicenter Study Grant.
Conflict of Interest Disclosures: Dr Yuya Matsue received an honorarium from Otsuka Pharmaceutical Co. Dr Makoto Suzuki received lecture honoraria from Otsuka Pharmaceutical Co, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Medtronic Japan Co, Boston Scientific Japan Co, and Fukuda Denshi. Dr Kazuki Yoshida receives tuition support jointly from the Japan Student Services Organization and Harvard T. H. Chan School of Public Health (partially supported by training grants from Pfizer, Takeda, Bayer, and PhRMA). Dr Kaoru Sugi received scholership fund from Daiichi-Sankyo Pharmaceutical and lecture honoraria from Bayer. Dr Steven R. Goldsmith received consulting fees, speaking fees, and research support from Otsuka USA and Otsuka-Japan. The other authors have nothing to disclose.
© 2016 Elsevier Inc.
Copyright 2017 Elsevier B.V., All rights reserved.
- Vasopressin antagonist
- acute heart failure
- renal function