Ginès Pere
Liver Unit, Hospital Clínic, University of Barcelona School of Medicine, Barcelona, Catalunya, Spain.
J Hepatol. 2007 Jun;46(6):1150-2. doi: 10.1016/j.jhep.2007.03.007. Epub 2007 Mar 28.
BACKGROUND/AIMS: Hyponatremia (serum sodium concentration, <135 mmol/L) is a predictor of death among patients with chronic heart failure and cirrhosis. At present, therapy for acute and chronic hyponatremia is often ineffective and poorly tolerated. We investigated whether tolvaptan, an orally active vasopressin V(2)-receptor antagonist that promotes aquaresis--excretion of electrolyte-free water--might be of benefit in hyponatremia.
In two multicenter, randomized, double-blind, placebo-controlled trials, the efficacy of tolvaptan was evaluated in patients with euvolemic or hypervolemic hyponatremia. Patients were randomly assigned to oral placebo (223 patients) or oral tolvaptan (225) at a dose of 15mg daily. The dose of tolvaptan was increased to 30 mg daily and then to 60 mg daily, if necessary, on the basis of serum sodium concentrations. The two primary end points for all patients were the change in the average daily area under the curve for the serum sodium concentration from baseline to day 4 and the change from baseline to day 30.
Serum sodium concentrations increased more in the tolvaptan group than in the placebo group during the first 4 days (P<0.001) and after the full 30 days of therapy (P<0.001). The condition of patients with mild or marked hyponatremia improved (P<0.001 for all comparisons). During the week after discontinuation of tolvaptan on day 30, hyponatremia recurred. Side effects associated with tolvaptan included increased thirst, dry mouth, and increased urination. A planned analysis that combined the two trials showed significant improvement from baseline to day 30 in the tolvaptan group according to scores on the Mental Component of the Medical Outcomes Study 12-item Short-Form General Health Survey.
In patients with euvolemic or hypervolemic hyponatremia, tolvaptan, an oral vasopressin V2-receptor antagonist, was effective in increasing serum sodium concentrations at day 4 and day 30. [Abstract reproduced by permission of N Engl J Med 2006;355:2099-2112].
背景/目的：低钠血症（血清钠浓度＜135mmol/L）是慢性心力衰竭和肝硬化患者死亡的一个预测因素。目前，急慢性低钠血症的治疗往往无效且耐受性差。我们研究了托伐普坦，一种口服活性血管加压素V₂受体拮抗剂，可促进无溶质水清除，对低钠血症是否有益。
在两项多中心、随机、双盲、安慰剂对照试验中，评估托伐普坦对血容量正常或血容量过多性低钠血症患者的疗效。患者被随机分配口服安慰剂（223例患者）或口服托伐普坦（225例），剂量为每日15mg。根据血清钠浓度，必要时将托伐普坦剂量增至每日30mg，然后增至每日60mg。所有患者的两个主要终点是从基线到第4天血清钠浓度曲线下平均每日面积的变化以及从基线到第30天的变化。
在治疗的前4天（P＜0.001）和整个30天治疗期结束后（P＜0.001），托伐普坦组血清钠浓度升高幅度大于安慰剂组。轻度或重度低钠血症患者的病情有所改善（所有比较P＜0.001）。在第30天停用托伐普坦后的一周内，低钠血症复发。与托伐普坦相关的副作用包括口渴增加、口干和尿量增加。一项合并两项试验的计划分析显示，根据医学结局研究12项简短形式一般健康调查的精神健康分量表评分，托伐普坦组从基线到第30天有显著改善。
对于血容量正常或血容量过多性低钠血症患者，口服血管加压素V₂受体拮抗剂托伐普坦在第4天和第30天可有效提高血清钠浓度。[摘要经《新英格兰医学杂志》2006年；355:2099 - 2112许可转载]
