当前位置:科学网首页 > 小柯机器人 >详情
心肌肌球蛋白激活剂Omecamtiv mecarbil治疗收缩期心力衰竭疗效显著
作者:小柯机器人 发布时间:2020/11/18 13:36:13

美国加州大学旧金山分校John R. Teerlink团队研究了心肌肌球蛋白激活剂Omecamtiv mecarbil治疗收缩期心力衰竭的疗效。2020年11月13日,该研究发表在《新英格兰医学杂志》上。

研究表明,选择性心肌肌球蛋白激活剂Omecamtiv mecarbil可改善心力衰竭伴射血分数降低患者的心功能。但其对心血管结局的影响尚不清楚。

研究组招募了8256例有症状的慢性心力衰竭且射血分数小于或等于35%的患者(住院患者和门诊患者),并将其随机分组,在标准心力衰竭治疗的基础上,分别接受Omecamtiv mecarbil或安慰剂治疗。主要结局为首次心力衰竭事件或心血管原因死亡的综合结局。

中位随访21.8个月后,Omecamtiv mecarbil组的4120例患者中有1523例(37.0%)发生了主要结局,安慰剂组的4112例患者中有1607例(39.1%),组间差异显著;心血管原因死亡的患者分别为808例(19.6%)和798例(19.4%),差异不显著。两组中的患者堪萨斯城心肌病问卷总症状评分与基线相比的变化均无显著差异。第24周时,与基线相比,Omecamtiv mecarbil组的中位N端前B型利钠肽水平变化比安慰剂组低10%,心脏肌钙蛋白I的中位水平比安慰剂组高4 ng/L。两组间心脏缺血性和室性心律不齐的发生率相差不大。

总之,对于心力衰竭伴射血分数降低的患者,接受Omecamtiv mecarbil治疗与安慰剂相比,发生心衰事件或心血管原因死亡的综合事件的风险较低。

附:英文原文

Title: Cardiac Myosin Activation with Omecamtiv Mecarbil in Systolic Heart Failure | NEJM

Author: John R. Teerlink, M.D.,, Rafael Diaz, M.D.,, G. Michael Felker, M.D., M.H.S.,, John J.V. McMurray, M.D.,, Marco Metra, M.D.,, Scott D. Solomon, M.D.,, Kirkwood F. Adams, M.D.,, Inder Anand, M.D., D.Phil.,, Alexandra Arias-Mendoza, M.D.,, Tor Biering-Srensen, M.D.,, Michael Bhm, M.D.,, Diana Bonderman, M.D.,, John G.F. Cleland, M.D.,, Ramon Corbalan, M.D.,, Maria G. Crespo-Leiro, M.D., Ph.D.,, Ulf Dahlstrm, M.D., Ph.D.,, Luis E. Echeverria, M.D.,, James C. Fang, M.D.,, Gerasimos Filippatos, M.D.,, Candida Fonseca, M.D., Ph.D.,, Eva Goncalvesova, M.D., Ph.D.,, Assen R. Goudev, M.D., Ph.D.,, Jonathan G. Howlett, M.D.,, David E. Lanfear, M.D.,, Jing Li, M.D., Ph.D.,, Mayanna Lund, M.D.,, Peter Macdonald, M.D., Ph.D.,, Viacheslav Mareev, M.D., Ph.D.,, Shin-ichi Momomura, M.D.,, Eileen O’Meara, M.D.,, Alexander Parkhomenko, M.D., Ph.D.,, Piotr Ponikowski, M.D., Ph.D.,, Felix J.A. Ramires, M.D., Ph.D.,, Pranas Serpytis, M.D., Ph.D.,, Karen Sliwa, M.D., Ph.D.,, Jindrich Spinar, M.D., Ph.D.,, Thomas M. Suter, M.D.,, Janos Tomcsanyi, M.D., Ph.D.,, Hans Vandekerckhove, M.D.,, Dragos Vinereanu, M.D., Ph.D.,, Adriaan A. Voors, M.D., Ph.D.,, Mehmet B. Yilmaz, M.D.,, Faiez Zannad, M.D., Ph.D.,, Lucie Sharpsten, Ph.D.,, Jason C. Legg, Ph.D.,, Claire Varin, M.D.,, Narimon Honarpour, M.D., Ph.D.,, Siddique A. Abbasi, M.D.,, Fady I. Malik, M.D., Ph.D.,, and Christopher E. Kurtz, M.D.

Issue&Volume: 2020-11-13

Abstract:

Background

The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown.

Methods

We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes.

Results

During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P=0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro–B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups.

Conclusions

Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo.

DOI: 10.1056/NEJMoa2025797

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2025797

 

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home