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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.

AbstractOBJECTIVES:
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).
AuthorsJames E Udelson, Cesare Orlandi, John Ouyang, Holly Krasa, Christopher A Zimmer, Geir Frivold, W Herbert Haught, Sheiba Meymandi, Cezar Macarie, Dimitar Raef, Patricia Wedge, Marvin A Konstam, Mihai Gheorghiade
JournalJournal of the American College of Cardiology (J Am Coll Cardiol) Vol. 52 Issue 19 Pg. 1540-5 (Nov 04 2008) ISSN: 1558-3597 [Electronic] United States
PMID19007589 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Receptors, Vasopressin
  • Tolvaptan
Topics
  • Administration, Oral
  • Aged
  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines (administration & dosage, adverse effects)
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Heart Failure, Systolic (diagnosis, drug therapy, mortality)
  • Heart Function Tests
  • Hemodynamics (drug effects, physiology)
  • Humans
  • International Cooperation
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Probability
  • Prospective Studies
  • Receptors, Vasopressin (administration & dosage)
  • Reference Values
  • Risk Assessment
  • Severity of Illness Index
  • Survival Rate
  • Tolvaptan
  • Treatment Outcome

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