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

• Published in: Journal of the American College of Cardiology 2008-11, Vol.52 (19), p.1540-1545
• Main Authors: UDELSON, James E, ORLANDI, Cesare, WEDGE, Patricia, KONSTAM, Marvin A, GHEORGHIADE, Mihai, OUYANG, John, KRASA, Holly, ZIMMER, Christopher A, FRIVOLD, Geir, HAUGHT, W. Herbert, MEYMANDI, Sheiba, MACARIE, Cezar, RAEF, Dimitar
• Format: Article
• Language: English
• Subjects: Administration, Oral; Aged; Angioplasty; Antidiuretic Hormone Receptor Antagonists; Benzazepines - administration & dosage; Benzazepines - adverse effects; Biological and medical sciences; Cardiology; Cardiology. Vascular system; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug dosages; Drug therapy; Enzymes; Female; Follow-Up Studies; Heart; Heart attacks; Heart failure; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Heart Failure, Systolic - diagnosis; Heart Failure, Systolic - drug therapy; Heart Failure, Systolic - mortality; Heart Function Tests; Hemodynamics - drug effects; Hemodynamics - physiology; Humans; International Cooperation; Male; Medical sciences; Middle Aged; Multivariate Analysis; Probability; Prospective Studies; Pulmonary arteries; Receptors, Vasopressin - administration & dosage; Reference Values; Risk Assessment; Severity of Illness Index; Statistical analysis; Survival Rate; Treatment Outcome; Veins & arteries
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2008.08.013

This study sought to assess the acute hemodynamic effect of vasopressin V(2) receptor antagonism. 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. 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. 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. 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).