Yuya Matsue1, Makoto Suzuki2, Sho Torii3, Satoshi Yamaguchi4, Seiji Fukamizu5, Yuichi Ono6, Hiroyuki Fujii7, Takeshi Kitai8, Toshihiko Nishioka9, Kaoru Sugi10, Yuko Onishi11, Makoto Noda12, Nobuyuki Kagiyama13, Yasuhiro Satoh14, Kazuki Yoshida15, Steven R Goldsmith16. 1. Department of Cardiology, Kameda Medical Center, Chiba, Japan. Electronic address: yuya8950@gmail.com. 2. Department of Cardiology, Kameda Medical Center, Chiba, Japan. 3. Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan. 4. Department of Cardiology, Tomishiro Central Hospital, Okinawa, Japan. 5. Department of Cardiology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan. 6. Department of Cardiology, Ome Municipal General Hospital, Tokyo, Japan. 7. Department of Cardiology, Yokohama Minami Kyosai Hospital, Kanagawa, Japan. 8. Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan. 9. Department of Cardiology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan. 10. Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan. 11. Department of Cardiology, Hiratsuka Kyosai Hospital, Kanagawa, Japan. 12. Department of Cardiology, Tokyo Yamate Medical Center, Tokyo, Japan. 13. Department of Cardiology, Sakakibara Heart Institute of Okayama, Okayama, Japan. 14. Department of Cardiology, National Disaster Medical Center, Tokyo, Japan. 15. Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA. 16. Division of Cardiology, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.
Abstract
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 60mL/min/1.73m(2)) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. RESULTS: During follow-up (636days, 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 30mL/min/1.73m(2) 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.
RCT Entities:
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 60mL/min/1.73m(2)) were randomized within 6h from hospitalization to either tolvaptan treatment for 2days or conventional treatment. The primary outcome was the combined endpoint of all-cause death and HF readmission. RESULTS: During follow-up (636days, 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 30mL/min/1.73m(2) 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.
Authors: Meaghan Lunney; Marinella Ruospo; Patrizia Natale; Robert R Quinn; Paul E Ronksley; Ioannis Konstantinidis; Suetonia C Palmer; Marcello Tonelli; Giovanni Fm Strippoli; Pietro Ravani Journal: Cochrane Database Syst Rev Date: 2020-02-27