Multicenter, randomized, double-blind, placebo-controlled study on the effect of oral tolvaptan on left ventricular dilation and function in patients with heart failure and systolic dysfunction

被引:125
作者
Udelson, James E.
McGrew, Frank A.
Flores, Enrique
Ibrahim, Hassan
Katz, Stewart
Koshkarian, Gregory
O'Brien, Terrence
Kronenberg, Marvin W.
Zimmer, Christopher
Orlandi, Cesare
Konstam, Marvin A.
机构
[1] Tufts Univ, New England Med Ctr, Sch Med, Div Cardiol, Boston, MA 02111 USA
[2] Stern Cardiovasc Ctr, Memphis, TN USA
[3] Georgia Heart Specialists, Covington, GA USA
[4] N Ohio Res Ltd, Sandusky, OH USA
[5] Yale Univ, Sch Med, New Haven, CT 06520 USA
[6] Desert Cardiol Tucson, Tucson, AZ USA
[7] Ralph Johnson VA Med Ctr, Charleston, SC USA
[8] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN USA
[9] Otsuka Amer Pharmaceut Inc, Rockville, MD USA
关键词
D O I
10.1016/j.jacc.2007.01.091
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objectives This study sought to examine the effects of vasopressin V-2 receptor antagonism with tolvaptan on the changes in left ventricular (LV) volumes over time. Background Vasopressin levels may be increased in patients with heart failure (HF) and may be a factor driving the progression of HF. Methods This was a multicenter, randomized, double-blind, placebo-controlled trial conducted to evaluate the effect of long-term administration of the vasopressin V-2-receptor antagonist tolvaptan (30 mg,/day) on reducing left ventricular end-diastolic volume (LVEDV) compared with placebo in patients with HF and reduced systolic function, using quantitative radionuclide ventriculography at baseline, repeated after 1 year of therapy, and repeated again approximately 1 week after withdrawal of study drug. Results A total of 120 patients were randomized to tolvaptan and 120 were randomized to placebo. In the placebo group, there was no change in LVEDV over the course of follow-up (change of 0.0 +/- 10.0 ml/m(2)). After 1 year of tolvaptan, there was a small reduction in LV volume (decrease of 1.8 +/- 10.7 ml/m(2)); the between-group difference was not significant (p = 0.21). During the course of the trial, there were 6 deaths (5%) and 21 HF hospitalizations (18%) in the tolvaptan group, compared with 11 deaths (9%) and 34 HF hospitalizations (28%) in the placebo group. In a time-to-event analysis, there was a significant favorable effect of tolvaptan on the composite of mortality or heart failure hospitalization (p < 0.03 by log-rank test). Conclusions In a well-treated population of stable HF patients, there was no significant effect of tolvaptan therapy on LV volumes observed during 1 year of therapy. Nonprespecified natural history data favored therapy with tolvaptan, with a reduction in the combined end point of mortality and heart failure hospitalization observed. (Multicenter, Randomized, Double-Blind, Placebo Controlled, Efficacy Study on the Effects of Tolvaptan on Left Ventricuiar Dilatation in Congestive Heart Failure Patients; http://clinicaltrials.gov/ct/ show/NCT00043758?order = 1; NCT00043758).
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收藏
页码:2151 / 2159
页数:9
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