title: Acute hemodynamic effects of tolvaptan, a vasopressin V2 receptor blocker, in patients with symptomatic heart failure and systolic dysfunction: an international, multicenter, randomized, placebo-controlled trial.
abstract: OBJECTIVE
  This study sought to assess the acute hemodynamic effect of vasopressin V(2) receptor antagonism.
  
  
  BACKGROUND
  In decompensated heart failure (HF), tolvaptan, a vasopressin V(2) receptor antagonist, has been shown to improve congestion. It has not yet been established whether these improvements may be associated with the hemodynamic effects of tolvaptan.
  
  
  METHODS
  A total of 181 patients with advanced HF on standard therapy were randomized to double-blind treatment with tolvaptan at a single oral dose (15, 30, or 60 mg) or placebo.
  
  
  RESULTS
  Tolvaptan at all doses significantly reduced pulmonary capillary wedge pressure (-6.4 +/- 4.1 mm Hg, -5.7 +/- 4.6 mm Hg, -5.7 +/- 4.3 mm Hg, and -4.2 +/- 4.6 mm Hg for the 15-mg, 30-mg, 60-mg, and placebo groups, respectively; p < 0.05 for all tolvaptan vs. placebo). Tolvaptan also reduced right atrial pressure (-4.4 +/- 6.9 mm Hg [p < 0.05], -4.3 +/- 4.0 mm Hg [p < 0.05], -3.5 +/- 3.6 mm Hg, and -3.0 +/- 3.0 mm Hg for the 15-mg, 30-mg, 60-mg, and placebo groups, respectively) and pulmonary artery pressure (-5.6 +/- 4.2 mm Hg, -5.5 +/- 4.1 mm Hg, -5.2 +/- 6.1 mm Hg, and -3.0 +/- 4.7 mm Hg for the 15-mg, 30-mg, 60-mg, and placebo groups, respectively; p < 0.05). Tolvaptan increased urine output by 3 h in a dose-dependent manner (p < 0.0001), without changes in renal function.
  
  
  CONCLUSIONS
  In patients with advanced HF, tolvaptan resulted in favorable but modest changes in filling pressures associated with a significant increase in urine output. These data provide mechanistic support for the symptomatic improvements noted with tolvaptan in patients with decompensated HF. (Heart Pressure Assessment Study With Tolvaptan to Treat Congestive Heart Failure; NCT00132886).
authors.affiliation: Division of Cardiology, Tufts Medical Center, Boston, Massachusetts 02111, USA. JUdelson@tuftsmedicalcenter.org
authors.forename: James E
authors.initials: JE
authors.lastname: Udelson
authors.forename: Cesare
authors.initials: C
authors.lastname: Orlandi
authors.forename: John
authors.initials: J
authors.lastname: Ouyang
authors.forename: Holly
authors.initials: H
authors.lastname: Krasa
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Zimmer
authors.forename: Geir
authors.initials: G
authors.lastname: Frivold
authors.forename: W Herbert
authors.initials: WH
authors.lastname: Haught
authors.forename: Sheiba
authors.initials: S
authors.lastname: Meymandi
authors.forename: Cezar
authors.initials: C
authors.lastname: Macarie
authors.forename: Dimitar
authors.initials: D
authors.lastname: Raef
authors.forename: Patricia
authors.initials: P
authors.lastname: Wedge
authors.forename: Marvin A
authors.initials: MA
authors.lastname: Konstam
authors.forename: Mihai
authors.initials: M
authors.lastname: Gheorghiade
mesh_terms: D000284:Administration, Oral; D000368:Aged; D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D054143:Heart Failure, Systolic / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D006334:Heart Function Tests; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007391:International Cooperation; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011336:Probability; D011446:Prospective Studies; D017483:Receptors, Vasopressin / Q000008:administration & dosage; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D017483:Receptors, Vasopressin; D000077602:Tolvaptan