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
J Am Coll Cardiol 2008; 52: 1540–1545 View citation
Objectives: This study sought to assess the acute hemodynamic effect of vasopressin V2 receptor antagonism.
Background: In decompensated heart failure (HF), tolvaptan, a vasopressin V2 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.
