title: Prognostic impact of early treatment with tolvaptan in patients with acute heart failure and renal dysfunction.
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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan. Electronic address: yuya8950@gmail.com.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Matsue
authors.affiliation: Department of Cardiology, Kameda Medical Center, Chiba, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology, Tokai University School of Medicine, Kanagawa, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Torii
authors.affiliation: Department of Cardiology, Tomishiro Central Hospital, Okinawa, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Cardiology, Tokyo Metropolitan Hiroo Hospital, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Fukamizu
authors.affiliation: Department of Cardiology, Ome Municipal General Hospital, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ono
authors.affiliation: Department of Cardiology, Yokohama Minami Kyosai Hospital, Kanagawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kitai
authors.affiliation: Department of Cardiology, Saitama Medical Center, Saitama Medical University, Kawagoe, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nishioka
authors.affiliation: Division of Cardiovascular Medicine, Toho University Ohashi Medical Center, Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugi
authors.affiliation: Department of Cardiology, Hiratsuka Kyosai Hospital, Kanagawa, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Onishi
authors.affiliation: Department of Cardiology, Tokyo Yamate Medical Center, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Noda
authors.affiliation: Department of Cardiology, Sakakibara Heart Institute of Okayama, Okayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Kagiyama
authors.affiliation: Department of Cardiology, National Disaster Medical Center, Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Satoh
authors.affiliation: Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Yoshida
authors.affiliation: Division of Cardiology, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldsmith
mesh_terms: D000208:Acute Disease; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D001552:Benzazepines / Q000008:administration & dosage / Q000009:adverse effects; D015897:Comorbidity; D061345:Early Medical Intervention / Q000379:methods; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051437:Renal Insufficiency / Q000175:diagnosis / Q000453:epidemiology; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D000077602:Tolvaptan
keywords: Acute heart failure; Neurohormonal activity; Prognosis; Renal dysfunction