Targeted anticytokine therapy in patients with chronic heart failure - Results of the Randomized Etanercept Worldwide evALuation (RENEWAL)
Targeted anticytokine therapy in patients with chronic heart failure - Results of the Randomized Etanercept Worldwide evALuation (RENEWAL)
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DOI：
10.1161/01.cir.0000124490.27666.b2
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发表时间：
2004-04-06
期刊：
影响因子：
37.8
通讯作者：
Fleming, T
中科院分区：
文献类型：
--
作者：
Mann, DL;McMurray, JJV;Fleming, T
背景-实验模型研究和初步临床经验提示可溶性肿瘤坏死因子拮抗剂依那西普在心力衰竭中可能具有治疗作用。方法和结果：纽约心脏协会II至IV级慢性心力衰竭和左心室射血分数小于或等于0.30的患者入组了2项临床试验，仅依那西普的剂量不同。在RECOVER试验中，患者接受安慰剂（n = 373）或依那西普皮下注射，剂量为每周25mg （n = 375）或每周两次25mg （n = 375）。在RENAISSANCE试验中，患者接受安慰剂（n = 309）、依那西普25 mg每周2次（n = 308）或依那西普25 mg每周3次（n = 308）。每个单独试验的主要终点是24周时的临床状态。还计划分析两种较高剂量依那西普对两项研究中因慢性心力衰竭而死亡或住院的综合结局的影响（续期）。根据预先规定的停止规则，两项试验都因缺乏效益而提前终止。依那西普对RENAISSANCE组（P = 0.17）或RECOVER组（P = 0.34）的临床状态没有影响，对RENEWAL组的死亡或慢性心力衰竭住院终点没有影响（依那西普与安慰剂的相对风险= 1.1,95% CI 0.91 ~ 1.33, P = 0.33）。结论：renew的结果排除了依那西普对慢性心力衰竭死亡率或住院率的临床相关益处。
Background - Studies in experimental models and preliminary clinical experience suggested a possible therapeutic role for the soluble tumor necrosis factor antagonist etanercept in heart failure.Methods and Results - Patients with New York Heart Association class II to IV chronic heart failure and a left ventricular ejection fraction less than or equal to0.30 were enrolled in 2 clinical trials that differed only in the doses of etanercept used. In RECOVER, patients received placebo (n = 373) or subcutaneous etanercept in doses of 25 mg every week (n = 375) or 25 mg twice per week (n = 375). In RENAISSANCE, patients received placebo (n = 309), etanercept 25 mg twice per week (n = 308), or etanercept 25 mg 3 times per week (n = 308). The primary end point of each individual trial was clinical status at 24 weeks. Analysis of the effect of the 2 higher doses of etanercept on the combined outcome of death or hospitalization due to chronic heart failure from the 2 studies was also planned (RENEWAL). On the basis of prespecified stopping rules, both trials were terminated prematurely owing to lack of benefit. Etanercept had no effect on clinical status in RENAISSANCE (P = 0.17) or RECOVER (P = 0.34) and had no effect on the death or chronic heart failure hospitalization end point in RENEWAL (etanercept to placebo relative risk = 1.1, 95% CI 0.91 to 1.33, P = 0.33).Conclusions - The results of RENEWAL rule out a clinically relevant benefit of etanercept on the rate of death or hospitalization due to chronic heart failure.