Effects of Serelaxin in Patients with Acute Heart Failure
Effects of Serelaxin in Patients with Acute Heart Failure
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DOI：
10.1056/nejmoa1801291
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发表时间：
2019-08-22
影响因子：
158.5
通讯作者：
Gimpelewicz, Claudio
中科院分区：
文献类型：
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作者：
Metra, Marco;Teerlink, John R.;Gimpelewicz, Claudio
背景色拉辛是人松弛蛋白-2的一种重组形式，松弛蛋白-2是一种血管扩张激素，有助于妊娠期间的心血管和肾脏适应。在这项多中心、双盲、安慰剂对照、事件驱动的多中心试验中，我们纳入了因急性心力衰竭住院并有呼吸困难、胸片血管充血、血浆钠尿肽浓度升高、轻至中度肾功能不全以及收缩压至少125毫米汞的患者，我们随机分配他们在出现症状后16小时内接受48小时静脉滴注舍拉辛(每公斤体重每天30微克)或安慰剂。两个主要终点是180天死于心血管疾病和5天心力衰竭恶化。结果共有6545名患者进入意向治疗分析。在第180天，塞来拉新组3274名患者中有285名(8.7%)死于心血管疾病，安慰剂组3271名患者中有290名(8.9%)死亡(风险比0.98；95%可信区间0.83至1.15；P=0.77)。在第5天，Serelaxin组227名患者(6.9%)和安慰剂组252名患者(7.7%)发生心力衰竭恶化(风险比0.89；95%可信区间0.75-1.07；P=0.19)。两组之间在180天的任何原因死亡的发生率、180天的心血管原因死亡的发生率、因心力衰竭或肾功能衰竭而再次住院的发生率以及指标住院时间方面没有显著差异。两组不良事件的发生率相似。结论在这项涉及因急性心力衰竭住院的患者的试验中，输注舍拉辛并不会导致180天后心血管原因死亡或5天后心力衰竭恶化的发生率低于安慰剂。(由诺华制药公司资助；RELAX-AHF-2 ClinicalTrials.gov编号，NCT01870778。)在一项随机试验中，6545名急性心力衰竭患者在标准治疗的基础上被分配给舍拉新或安慰剂。两组患者在180天后因心血管原因死亡或在5天后心力衰竭恶化的发生率没有显著差异。
BackgroundSerelaxin is a recombinant form of human relaxin-2, a vasodilator hormone that contributes to cardiovascular and renal adaptations during pregnancy. Previous studies have suggested that treatment with serelaxin may result in relief of symptoms and in better outcomes in patients with acute heart failure.MethodsIn this multicenter, double-blind, placebo-controlled, event-driven trial, we enrolled patients who were hospitalized for acute heart failure and had dyspnea, vascular congestion on chest radiography, increased plasma concentrations of natriuretic peptides, mild-to-moderate renal insufficiency, and a systolic blood pressure of at least 125 mm Hg, and we randomly assigned them within 16 hours after presentation to receive either a 48-hour intravenous infusion of serelaxin (30 mu g per kilogram of body weight per day) or placebo, in addition to standard care. The two primary end points were death from cardiovascular causes at 180 days and worsening heart failure at 5 days.ResultsA total of 6545 patients were included in the intention-to-treat analysis. At day 180, death from cardiovascular causes had occurred in 285 of the 3274 patients (8.7%) in the serelaxin group and in 290 of the 3271 patients (8.9%) in the placebo group (hazard ratio, 0.98; 95% confidence interval [CI], 0.83 to 1.15; P=0.77). At day 5, worsening heart failure had occurred in 227 patients (6.9%) in the serelaxin group and in 252 (7.7%) in the placebo group (hazard ratio, 0.89; 95% CI, 0.75 to 1.07; P=0.19). There were no significant differences between the groups in the incidence of death from any cause at 180 days, the incidence of death from cardiovascular causes or rehospitalization for heart failure or renal failure at 180 days, or the length of the index hospital stay. The incidence of adverse events was similar in the two groups.ConclusionsIn this trial involving patients who were hospitalized for acute heart failure, an infusion of serelaxin did not result in a lower incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days than placebo. (Funded by Novartis Pharma; RELAX-AHF-2 ClinicalTrials.gov number, NCT01870778.)In a randomized trial, 6545 patients with acute heart failure were assigned to either serelaxin or placebo in addition to standard care. There were no significant differences between the two groups in the incidence of death from cardiovascular causes at 180 days or worsening heart failure at 5 days.