Effect of Vericiguat, a Soluble Guanylate Cyclase Stimulator, on Natriuretic Peptide Levels in Patients With Worsening Chronic Heart Failure and Reduced Ejection Fraction

医学 耐受性 射血分数 心力衰竭 临床终点 随机对照试验 利尿剂 利钠肽 内科学 心脏病学 不利影响 安慰剂 病理 替代医学
作者
Mihai Gheorghiade,Stephen J. Greene,Javed Butler,Gerasimos Filippatos,Carolyn S.P. Lam,Aldo P. Maggioni,Piotr Ponikowski,Sanjiv J. Shah,Scott D. Solomon,Elisabeth Kraigher‐Krainer,Eliana T. Samano,Katharina Müller,Lothar Roessig,Burkert Pieske
出处
期刊:JAMA [American Medical Association]
卷期号:314 (21): 2251-2251 被引量:325
标识
DOI:10.1001/jama.2015.15734
摘要

Worsening chronic heart failure (HF) is a major public health problem.To determine the optimal dose and tolerability of vericiguat, a soluble guanylate cyclase stimulator, in patients with worsening chronic HF and reduced left ventricular ejection fraction (LVEF).Dose-finding phase 2 study that randomized 456 patients across Europe, North America, and Asia between November 2013 and January 2015, with follow-up ending June 2015. Patients were clinically stable with LVEF less than 45% within 4 weeks of a worsening chronic HF event, defined as worsening signs and symptoms of congestion and elevated natriuretic peptide level requiring hospitalization or outpatient intravenous diuretic.Placebo (n = 92) or 1 of 4 daily target doses of oral vericiguat (1.25 mg [n = 91], 2.5 mg [n = 91], 5 mg [n = 91], 10 mg [n = 91]) for 12 weeks.The primary end point was change from baseline to week 12 in log-transformed level of N-terminal pro-B-type natriuretic peptide (NT-proBNP). The primary analysis specified pooled comparison of the 3 highest-dose vericiguat groups with placebo, and secondary analysis evaluated a dose-response relationship with vericiguat and the primary end point.Overall, 351 patients (77.0%) completed treatment with the study drug with valid 12-week NT-proBNP levels and no major protocol deviation and were eligible for primary end point evaluation. In primary analysis, change in log-transformed NT-proBNP levels from baseline to week 12 was not significantly different between the pooled vericiguat group (log-transformed: baseline, 7.969; 12 weeks, 7.567; difference, -0.402; geometric means: baseline, 2890 pg/mL; 12 weeks, 1932 pg/mL) and placebo (log-transformed: baseline, 8.283; 12 weeks, 8.002; difference, -0.280; geometric means: baseline, 3955 pg/mL; 12 weeks, 2988 pg/mL) (difference of means, -0.122; 90% CI, -0.32 to 0.07; ratio of geometric means, 0.885, 90% CI, 0.73-1.08; P = .15). The exploratory secondary analysis suggested a dose-response relationship whereby higher vericiguat doses were associated with greater reductions in NT-proBNP level (P < .02). Rates of any adverse event were 77.2% and 71.4% among the placebo and 10-mg vericiguat groups, respectively.Among patients with worsening chronic HF and reduced LVEF, compared with placebo, vericiguat did not have a statistically significant effect on change in NT-proBNP level at 12 weeks but was well-tolerated. Further clinical trials of vericiguat based on the dose-response relationship in this study are needed to determine the potential role of this drug for patients with worsening chronic HF.clinicaltrials.gov Identifier: NCT01951625.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
1秒前
汉堡包应助NOTHING采纳,获得10
1秒前
SYLH应助科研通管家采纳,获得50
1秒前
quhayley应助科研通管家采纳,获得10
1秒前
爆米花应助科研通管家采纳,获得10
1秒前
坦率的匪应助科研通管家采纳,获得10
2秒前
田様应助科研通管家采纳,获得10
2秒前
SYLH应助科研通管家采纳,获得50
2秒前
orixero应助科研通管家采纳,获得10
2秒前
SYLH应助科研通管家采纳,获得50
2秒前
思源应助科研通管家采纳,获得10
2秒前
2秒前
隐形曼青应助科研通管家采纳,获得10
2秒前
czh应助科研通管家采纳,获得10
2秒前
赘婿应助科研通管家采纳,获得10
2秒前
华仔应助科研通管家采纳,获得10
2秒前
科研通AI2S应助科研通管家采纳,获得10
2秒前
3秒前
SYLH应助科研通管家采纳,获得50
3秒前
大模型应助科研通管家采纳,获得10
3秒前
3秒前
斯文败类应助Keyl采纳,获得10
3秒前
褪黑素应助科研通管家采纳,获得10
3秒前
完美世界应助科研通管家采纳,获得10
3秒前
3秒前
3秒前
3秒前
3秒前
3秒前
3秒前
3秒前
3秒前
3秒前
3秒前
努力科研霸王龙完成签到 ,获得积分10
4秒前
nns关闭了nns文献求助
4秒前
田様应助jiabaoyu采纳,获得10
5秒前
脑洞疼应助林林林林采纳,获得10
5秒前
xiaoxiao完成签到,获得积分10
5秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988732
求助须知:如何正确求助?哪些是违规求助? 3531027
关于积分的说明 11252281
捐赠科研通 3269732
什么是DOI,文献DOI怎么找? 1804764
邀请新用户注册赠送积分活动 881869
科研通“疑难数据库(出版商)”最低求助积分说明 809021