title: Efficacy and safety of tolvaptan in heart failure patients with sustained volume overload despite the use of conventional diuretics: a phase III open-label study.
abstract: OBJECTIVE
  Volume overload is a common complication associated with heart failure (HF) and is recommended to be treated with loop or thiazide diuretics. However, use of diuretics can cause serum electrolyte imbalances and diuretic resistance. Tolvaptan, a selective, oral, non-peptide vasopressin V2-receptor antagonist, offers a new option for treating volume overload in HF patients. The aim of this study was to investigate the efficacy and safety of tolvaptan in Japanese HF patients with volume overload.
  
  
  METHODS
  Fifty-one HF patients with volume overload, despite using conventional diuretics, were treated with 15 mg/day tolvaptan for 7 days. If the response was insufficient at Day 7, tolvaptan was continued for a further 7 days at either 15 mg/day or 30 mg/day. Outcomes included changes in body weight, symptoms and safety parameters.
  
  
  RESULTS
  Thirty-six patients discontinued treatment within 7 days, therefore 15 patients entered the second phase of treatment. In two patients, tolvaptan was increased to 30 mg/day after 7 days. Body weight was reduced on Day 7 (-1.95 ± 1.98 kg; n = 41) and Day 14 (-2.35 ± 1.44 kg; n = 11, 15 mg/day). Symptoms of volume overload, including lower limb edema, pulmonary congestion, jugular venous distention and hepatomegaly, were improved by tolvaptan treatment for 7 or 14 days. Neither tolvaptan increased the incidence of severe or serious adverse events when administered for 7-14 days.
  
  
  CONCLUSIONS
  This study confirms the efficacy and safety of 15 mg/day tolvaptan for 7-14 days in Japanese HF patients with volume overload despite conventional diuretics.
authors: Cardiovascular Center, Osaka General Medical Center, 3-1-56 Bandai-Higashi, Sumiyoshi-ku, Osaka, 558-8558, Japan. fukunami@gh.opho.jp
authors: Masatake
authors: M
authors: Fukunami
authors: Masunori
authors: M
authors: Matsuzaki
authors: Masatsugu
authors: M
authors: Hori
authors: Tohru
authors: T
authors: Izumi
mesh_terms: D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D044466:Asian People; D001552:Benzazepines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004232:Diuretics / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004489:Edema, Cardiac / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000652:urine; D006801:Humans; D008297:Male; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood; D000077602:Tolvaptan
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D000077602:Tolvaptan; D012964:Sodium; D003404:Creatinine; D011188:Potassium