现在的位置: 首页时讯速递, 进展交流>正文
[NEJM发表论文]重组松弛素不能降低急性心衰患者180天病死率
2019年09月02日 时讯速递, 进展交流 暂无评论

ORIGINAL ARTICLE

Effects of Serelaxin in Patients with Acute Heart Failure

Marco Metra, John R. Teerlink, Gad Cotter, et al

N Engl J Med 2019; 381:716-726
DOI: 10.1056/NEJMoa1801291

Abstract

BACKGROUND 背景

Serelaxin 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.

松弛素是一种重组人松弛素-2。作为一种具有血管扩张作用的激素,松弛素在妊娠期心血管和肾脏的适应性反应中发挥作用。既往研究提示,松弛素治疗能够缓解急性心衰患者的临床症状并改善预后。

METHODS 方法

In 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 μg 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.

这是一项多中心、双盲、安慰剂对照的事件驱动研究。我们纳入因急性心衰入院的患者,患者表现呼吸困难,胸片显示血管充血,血浆利钠肽水平升高,轻至中度肾功能不全,且收缩压至少125 mmHg。患者在就诊后16小时内接受随机分组,除标准治疗外,分别使用48小时静脉输注松弛素(30 μg/kg/d)或安慰剂。研究设置2项主要预后终点,即180天心血管事件导致死亡,以及5天内心衰加重。

RESULTS 结果

A 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.

共有6545名患者纳入意向治疗分析。至180天时,松弛素组3274名患者中285名(8.7%),以及安慰剂组3271名患者中290名(8.9%)因心血管原因导致死亡(风险比,0.98;95% 可信区间[CI], 0.83 to 1.15; P=0.77)。至第5天时,松弛素组227名患者 (6.9%) 及安慰剂组252名患者 (7.7%) 出现心衰加重(风险比0.89;95% CI, 0.75 to 1.07;P=0.19)。两组间180天全因病死率、心血管原因病死率或因心衰或肾衰再入院率,以及本次住院日均无显著差异。两组不良事件发生率相似。

CONCLUSIONS 结论

In 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)

在这项纳入因急性心衰入院的患者的研究中,与安慰剂相比,输注松弛素不能减少180天因心血管事件导致的死亡或5天时心衰加重。

[评论](仅代表个人观点)

  • 我们一直没有能够改善急性心衰患者临床预后的药物
  • 有关松弛素的RELAX-AHF研究发现,松弛素能够降低急性心衰患者6个月的病死率(7.3% vs. 11.3%)
  • 2013年6月,松弛素被FDA授予了治疗急性心衰的突破性药物资格,随后在俄罗斯获批上市,商品名为Reasanz
  • 然而,2014年,松弛素先后被FDA和欧盟拒绝上市,均要求诺华提供Serelaxin可以预防心脏疾病恶化的更多证据
  • 2017年3月22日,诺华公司根据本研究(RELAX-AHF-2)研究结果宣布,研究未能到达主要终点。在标准治疗的基础上添加serelaxin不能降低急性心衰(AHF)患者的180天心血管死亡率和5天心衰恶化

给我留言

您必须 [ 登录 ] 才能发表留言!

×
腾讯微博