Effects of oral tolvaptan in patients hospitalized for worsening heart failure - The EVEREST outcome trial
Effects of oral tolvaptan in patients hospitalized for worsening heart failure - The EVEREST outcome trial
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DOI：
10.1001/jama.297.12.1319
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发表时间：
2007-03-28
影响因子：
120.7
通讯作者：
Orlandi, Cesare
中科院分区：
文献类型：
--
作者：
Konstam, Marvin A.;Gheorghiade, Mihai;Orlandi, Cesare
背景血管加压素在心力衰竭中介导液体滞留。托伐普坦，一种血管加压素V-2受体阻滞剂，显示出治疗心力衰竭的希望。目的研究托伐普坦在心力衰竭住院患者中的应用效果。设计、设置和参与者使用托伐普坦(珠穆朗玛峰)进行心力衰竭结局研究，这是一项事件驱动、随机、双盲、安慰剂对照研究。结果试验包括2个短期临床状态研究中的4133名患者，他们在2003年10月7日至2006年2月3日期间因心力衰竭住院，在北美、南美和欧洲的359个地点随机分组，并在长期治疗期间进行跟踪。干预在入院48小时内，患者被随机分配到在标准治疗的基础上服用托伐普坦，每天30 mg(n=2072)，或安慰剂(n=2061)，持续至少60天。主要结果衡量双主要终点是全原因死亡率(优势和非劣势)和心血管死亡或因心力衰竭住院(仅优势)。结果随访9.9个月，托伐普坦组537例(25.9%)死亡，安慰剂组543例(26.3%)死亡(危险比0.98；95%可信区间0.87-1.11；P=.68)。死亡率差异的可信上限为1.25(P<；.001)。871名托伐普坦患者(42.0%)和829名安慰剂组患者(40.2%；危险比，1.04；95%可信区间，0.95-1.14)发生了心血管死亡或因心力衰竭住院。55)。心血管死亡率、心血管死亡或住院和心力衰竭恶化的次要终点也没有区别。托伐普坦显著改善了第1天患者评估的呼吸困难、第1天体重和第7天水肿的次要终点。在低钠血症患者中，血钠水平显著升高。堪萨斯城心肌病问卷的总体总分在门诊第1周没有改善，但体重和血钠效应在出院后很长一段时间内持续存在。托伐普坦引起口渴和口干，但两组主要不良事件的发生率相似。结论托伐普坦用于心力衰竭住院患者的急诊治疗，对长期死亡率和心力衰竭相关的发病率没有影响。
Context Vasopressin mediates fluid retention in heart failure. Tolvaptan, a vasopressin V-2 receptor blocker, shows promise for management of heart failure.Objective To investigate the effects of tolvaptan initiated in patients hospitalized with heart failure.Design, Setting, and Participants The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study With Tolvaptan (EVEREST), an event-driven, randomized, double-blind, placebo-controlled study. The outcome trial comprised 4133 patients within 2 short-term clinical status studies, who were hospitalized with heart failure, randomized at 359 North American, South American, and European sites between October 7, 2003, and February 3, 2006, and followed up during long-term treatment.Intervention Within 48 hours of admission, patients were randomly assigned to receive oral tolvaptan, 30 mg once per day (n = 2072), or placebo (n = 2061) for a minimum of 60 days, in addition to standard therapy.Main Outcome Measures Dual primary end points were all-cause mortality (superiority and noninferiority) and cardiovascular death or hospitalization for heart failure (superiority only). Secondary end points included changes in dyspnea, body weight, and edema.Results During amedian follow-up of 9.9 months, 537 patients (25.9%) in the tolvaptan group and 543 (26.3%) in the placebo group died (hazard ratio, 0.98; 95% confidence interval [CI], 0.87- 1.11; P = .68). The upper confidence limit for the mortality difference was within the prespecified noninferiority margin of 1.25 (P < .001). The composite of cardiovascular death or hospitalization for heart failure occurred in 871 tolvaptan group patients (42.0%) and 829 placebo group patients (40.2%; hazard ratio, 1.04; 95% CI, 0.95-1.14; P =. 55). Secondary end points of cardiovascular mortality, cardiovascular death or hospitalization, and worsening heart failure were also not different. Tolvaptan significantly improved secondary end points of day 1 patient-assessed dyspnea, day 1 body weight, and day 7 edema. In patients with hyponatremia, serum sodium levels significantly increased. The Kansas City Cardiomyopathy Questionnaire overall summary score was not improved at outpatient week 1, but body weight and serum sodium effects persisted long after discharge. Tolvaptan caused increased thirst and dry mouth, but frequencies of major adverse events were similar in the 2 groups.Conclusion Tolvaptan initiated for acute treatment of patients hospitalized with heart failure had no effect on long-term mortality or heart failure-related morbidity.