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Vericiguat并不能改善心力衰竭和射血分数保留患者的生活质量
作者:小柯机器人 发布时间:2020/10/24 22:24:31

美国密西西比大学医学中心Javed Butler联合加拿大阿尔伯塔大学Paul W. Armstrong团队比较了Vericiguat与安慰剂治疗心力衰竭和射血分数保留患者对生活质量的影响。2020年10月20日,该研究发表在《美国医学会杂志》上。

心力衰竭和射血分数保留(HFpEF)的患者有很高的死亡、住院、功能和生活质量降低的风险。

为了评估口服可溶性鸟苷酸环化酶刺激剂对堪萨斯城心肌病问卷(KCCQ)的身体受限评分(PLS)的效果,2018年6月15日到2019年3月27日,研究组在21个国家/地区的167个临床机构进行了一项临床2b期、随机、双盲、安慰剂对照的多中心试验。

研究组共招募了789例慢性HFpEF、左心室射血分数45%及以上,伴有纽约心脏协会II-III级症状、最近6个月内失代偿以及利钠肽水平升高的患者,将其随机分组,其中262例接受安慰剂治疗,264例接受每日Vericiguat 15mg治疗,263例接受每日Vericiguat 10mg治疗。主要结局为治疗24周后KCCQ PLS的变化(范围0-100;数值越高表示功能越好)。

789名患者的平均年龄为72.7岁,其中385名(49%)为女性,平均EF为56%,N端前脑利钠肽水平中位数为1403 pg/mL,761例(96.5%)完成了试验。15 mg/d Vericiguat组、10 mg/d Vericiguat组和安慰剂组在基线和24周时的KCCQ PLS平均值分别为60.0和68.3、57.3和69.0、59.0和67.1,最小二乘均值变化分别为5.5、6.4和6.9。15 mg/d Vericiguat组和安慰剂组间的最小二乘均值差为-1.5,而10 mg/d Vericiguat组和安慰剂组间的均值差为-0.5。

15 mg/d Vericiguat组、10 mg/d Vericiguat组和安慰剂组在基线和24周步行6分钟的平均距离分别为295.0 m和311.8m、292.1 m和318.3 m、295.8 m和311.4 m,最小二乘均值变化分别为5.0 m、8.7 m和10.5 m。15 mg/d Vericiguat组和安慰剂组间的最小二乘均值差为-5.5 m,而10 mg/d Vericiguat组和安慰剂组间的均值差为-1.8m。15 mg/d Vericiguat组出现症状性低血压的患者比例为6.4%,10 mg/d Verigguat组为4.2%,安慰剂组为3.4%;三组中晕厥的发生率分别为1.5%、0.8%和0.4%。

总之,在有HFpEF和最近代偿失调的患者中,与安慰剂相比,Vericiguat 15 mg/d或10 mg/d剂量进行治疗24周,并不能改善KCCQ的身体受限评分。

附:英文原文

Title: Effect of Vericiguat vs Placebo on Quality of Life in Patients With Heart Failure and Preserved Ejection Fraction: The VITALITY-HFpEF Randomized Clinical Trial

Author: Paul W. Armstrong, Carolyn S. P. Lam, Kevin J. Anstrom, Justin Ezekowitz, Adrian F. Hernandez, Christopher M. O’Connor, Burkert Pieske, Piotr Ponikowski, Sanjiv J. Shah, Scott D. Solomon, Adriaan A. Voors, Lilin She, Vanja Vlajnic, Francine Carvalho, Luke Bamber, Robert O. Blaustein, Lothar Roessig, Javed Butler, VITALITY-HFpEF Study Group

Issue&Volume: 2020/10/20

Abstract:

Importance  Patients with heart failure and preserved ejection fraction (HFpEF) are at high risk of mortality, hospitalizations, and reduced functional capacity and quality of life.

Objective  To assess the efficacy of the oral soluble guanylate cyclase stimulator vericiguat on the physical limitation score (PLS) of the Kansas City Cardiomyopathy Questionnaire (KCCQ).

Design, Setting, and Participants  Phase 2b randomized, double-blind, placebo-controlled, multicenter trial of 789 patients with chronic HFpEF and left ventricular ejection fraction 45% or higher with New York Heart Association class II-III symptoms, within 6 months of a recent decompensation (HF hospitalization or intravenous diuretics for HF without hospitalization), and with elevated natriuretic peptides, enrolled at 167 sites in 21 countries from June 15, 2018, through March 27, 2019; follow-up was completed on November 4, 2019.

Interventions  Patients were randomized to receive vericiguat, up-titrated to 15-mg (n=264) or 10-mg (n=263) daily oral dosages, compared with placebo (n=262) and randomized 1:1:1.

Main Outcomes and Measures  The primary outcome was change in the KCCQ PLS (range, 0-100; higher values indicate better functioning) after 24 weeks of treatment. The secondary outcome was 6-minute walking distance from baseline to 24 weeks.

Results  Among 789 randomized patients, the mean age was 72.7 (SD, 9.4) years; 385 (49%) were female; mean EF was 56%; and median N-terminal pro–brain natriuretic peptide level was 1403 pg/mL; 761 (96.5%) completed the trial. The baseline and 24-week KCCQ PLS means for the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 60.0 and 68.3, 57.3 and 69.0, and 59.0 and 67.1, respectively, and the least-squares mean changes were 5.5, 6.4, and 6.9, respectively. The least-squares mean difference in scores between the 15-mg/d vericiguat and placebo groups was 1.5 (95% CI, 5.5 to 2.5; P=.47) and between the 10-mg/d vericiguat and placebo groups was 0.5 (95% CI, 4.6 to 3.5; P=.80). The baseline and 24-week 6-minute walking distance mean scores in the 15-mg/d vericiguat, 10-mg/d vericiguat, and placebo groups were 295.0 m and 311.8m , 292.1 m and 318.3 m, and 295.8 m and 311.4 m, and the least-squares mean changes were 5.0 m, 8.7 m, and 10.5 m, respectively. The least-squares mean difference between the 15-mg/d vericiguat and placebo groups was 5.5 m (95% CI, 19.7 m to 8.8 m; P=.45) and between the 10-mg/d vericiguat and placebo groups was 1.8 m (95% CI, 16.2 m to 12.6 m; P=.81), respectively. The proportions of patients who experienced symptomatic hypotension were 6.4% in the 15-mg/d vericiguat group, 4.2% in the 10-mg/d vericiguat group, and 3.4% in the placebo group; those with syncope were 1.5%, 0.8%, and 0.4%, respectively.

Conclusions and Relevance  Among patients with HFpEF and recent decompensation, 24-week treatment with vericiguat at either 15-mg/d or 10-mg/d dosages compared with placebo did not improve the physical limitation score of the KCCQ.

DOI: 10.1001/jama.2020.15922

Source: https://jamanetwork.com/journals/jama/article-abstract/2771900

期刊信息

JAMA-Journal of The American Medical Association:《美国医学会杂志》,创刊于1883年。隶属于美国医学协会,最新IF:51.273
官方网址:https://jamanetwork.com/
投稿链接:http://manuscripts.jama.com/cgi-bin/main.plex