发布日期：2008 年 11 月
英文标题：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.
作者：Udelson JE, Orlandi C, Ouyang J, Krasa H, Zimmer CA, Frivold G, Haught WH, Meymandi S, Macarie C, Raef D, Wedge P, Konstam MA, Gheorghiade M.
出处：J Am Coll Cardiol. 2008 Nov 4;52(19):1540-5.
内容介绍：在接受标准治疗中发生心力衰竭的患者，被随机分为托伐普坦 15、30、60 mg 组和安慰剂组，结果与安慰剂相比，托伐普坦 3 组均能有效降低 PCWP、右房压力和肺动脉压力，托伐普坦 3 h 内增加尿量呈剂量依赖性并且对肾功能无影响，提示托伐普坦用于失代偿心力衰竭患者，可以安全有效地改善血流动力学，缓解症状。
摘要展示：
OBJECTIVES: 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..
