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.
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).
Udelson
James E
JE
Division of Cardiology, Tufts Medical Center, Boston, Massachusetts 02111, USA. JUdelson@tuftsmedicalcenter.org
Orlandi
Cesare
C
Ouyang
John
J
Krasa
Holly
H
Zimmer
Christopher A
CA
Frivold
Geir
G
Haught
W Herbert
WH
Meymandi
Sheiba
S
Macarie
Cezar
C
Raef
Dimitar
D
Wedge
Patricia
P
Konstam
Marvin A
MA
Gheorghiade
Mihai
M
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
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D017483:Receptors, Vasopressin; D000077602:Tolvaptan