Background Renal dysfunction is a common comorbidity in acute heart failure (AHF) patients. The prognostic significance of early treatment with tolvaptan in AHF patients complicated with renal dysfunction has not been elucidated. Methods Post hoc analysis was performed on a randomized clinical study for prespecified prognostic endpoints and prespecified subgroups. 217 AHF patients with renal dysfunction (eGFR 15 to 60 mL/min/1.73 m2) were randomized within 6 h from hospitalization to either tolvaptan treatment for 2 days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. Results During follow-up (636 days, median) 99 patients experienced combined endpoint and 53 patients died. There was no significant difference in event-free survival rate for either the combined events (Log-rank: P = 0.197) or all-cause death (Log-rank: P = 0.894) between tolvaptan and conventional groups. In prespecified subgroup analysis, in patients whose BUN/creatinine ratio was above the median (> 20), tolvaptan significantly reduced the risk of combined events (HR: 0.52, 95% CI: 0.30–0.91, P = 0.021) with a significant interaction (P value for interaction = 0.045). Likewise, in patients whose eGFR was 30 mL/min/1.73 m2 or above, tolvaptan reduced the risk of combined events (HR: 0.54, 95% CI: 0.32–0.90, P = 0.017) with a significant interaction (P value for interaction = 0.015). Conclusion Short-term use of tolvaptan in acute-phase in AHF with renal dysfunction showed a neutral effect on prognosis. Patients with relatively preserved renal function and relatively high BUN/creatinine ratios are potentially favorable subgroups for treatment with tolvaptan.
Bibliographical noteFunding Information:
AQUAMARINE study was funded by the Japan Heart Foundation Multicenter Study Grant.
Dr. Yuya Matsue is supported by JSPS (Japan Society for the Promotion of Science) Postdoctoral Fellowships for Research Abroad, and received a honorarium from Otsuka Pharmaceutical Co. Dr. Makoto Suzuki received lectures honoraria from Otsuka Pharmaceutical Co., Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Medtronic Japan Co., Ltd., Boston Scientific Japan Co., Ltd., and Fukuda Denshi. Dr. Yuichi Ono received lectures honoraria from Medtronic Japan Co., Ltd. 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 scholarship fund from Daiichi-Sankyo Pharmaceutical and lectures 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 Ireland Ltd
Copyright 2017 Elsevier B.V., All rights reserved.
- Acute heart failure
- Neurohormonal activity
- Renal dysfunction