发布日期：2004 年 4 月
英文标题：Effects of tolvaptan, a vasopressin antagonist, in patients hospitalized with worsening heart failure: a randomized controlled trial.
作者：Gheorghiade M, Gattis WA, O'Connor CM, Adams KF Jr, Elkayam U, Barbagelata A, Ghali JK, Benza RL, McGrew FA, Klapholz M, Ouyang J, Orlandi C; Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure (ACTIV in CHF) Investigators.
出处：JAMA. 2004 Apr 28;291(16):1963-71.
内容介绍：在心力衰竭住院患者中，将托伐普坦组与常规治疗合用，较单用常规疗法能明显减轻体质量，又不会影响血压、心率、电解质和肾功能。托伐普坦虽不能降低出院后心力衰竭恶化率，但可降低肾功能不全和严重全身充血导致的病死率。
摘要展示：
CONTEXT: Nearly 1 million hospitalizations for chronic heart failure occur yearly in the United States, with most related to worsening systemic congestion. Diuretic use, the mainstay therapy for congestion, is associated with electrolyte abnormalities and worsening renal function. In contrast to diuretics, the vasopressin antagonist tolvaptan may increase net volume loss in heart failurewithout adversely affecting electrolytes and renal function.
OBJECTIVE: To evaluate the short- and intermediate-term effects of tolvaptan in patients hospitalized with heart failure.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, phase 2 trial conducted at 45 centers in the United States and Argentina and enrolling 319 patients with left ventricular ejection fraction of less than 40% and hospitalizedfor heart failure with persistent signs and symptoms of systemic congestion despite standard therapy.
INTERVENTION: After admission, patients were randomized to receive 30, 60, or 90 mg/d of oral tolvaptan or placebo in addition to standard therapy, including diuretics. The study drug was continued for up to 60 days.
MAIN OUTCOME MEASURES: In-hospital outcome was change in body weight at 24 hours after randomization; outpatient outcome was worsening heart failure (defined as death, hospitalization, or unscheduled visits for heart failure) at 60 days after randomization.
RESULTS: Median (interquartile range) body weight at 24 hours after randomization decreased by -1.80 (-3.85 to -0.50), -2.10 (-3.10 to -0.85), -2.05 (-2.80 to -0.60), and -0.60 (-1.60 to 0.00) kg in the groups receiving tolvaptan 30, 60, and 90 mg/d, and placebo, respectively (P< or =.008 for all tolvaptan groups vs placebo). The decrease in body weight with tolvaptan was not associated with changes in heart rate or blood pressure, nor did it result in hypokalemia or worsening renal function. There were no differences in worsening heart failure at 60 days between the tolvaptan and placebo groups (P =.88 for trend). In post hoc analysis, 60-day mortality was lower in tolvaptan-treated patients with renal dysfunction or severe systemic congestion.
CONCLUSION: Tolvaptan administered in addition to standard therapy may hold promise for management of systemic congestion in patients hospitalized for heart failure.
