沙库巴曲缬沙坦治疗射血分数降低的心力衰竭患者的效果：一项随机临床试验。

Effect of Treatment With Sacubitril/Valsartan in Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial.

机构信息

Department of Medicine, Washington University in St Louis, St Louis, Missouri.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

出版信息

JAMA Cardiol. 2022 Jan 1;7(1):17-25. doi: 10.1001/jamacardio.2021.4567.

DOI:10.1001/jamacardio.2021.4567

PMID:34730769

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8567189/

Abstract

IMPORTANCE

The use of sacubitril/valsartan is not endorsed by practice guidelines for use in patients with New York Heart Association class IV heart failure with a reduced ejection fraction because of limited clinical experience in this population.

OBJECTIVE

To compare treatment with sacubitril/valsartan treatment with valsartan in patients with advanced heart failure and a reduced ejection fraction and recent New York Heart Association class IV symptoms.

DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial was conducted; a total of 335 patients with advanced heart failure were included. The trial began on March 2, 2017, and was stopped early on March 23, 2020, owing to COVID-19 risk.

INTERVENTION

Patients were randomized to receive sacubitril/valsartan (target dose, 200 mg twice daily) or valsartan (target dose, 160 mg twice daily) in addition to recommended therapy.

MAIN OUTCOMES AND MEASURES

The area under the curve (AUC) for the ratio of N-terminal pro-brain natriuretic peptide (NT-proBNP) compared with baseline measured through 24 weeks of therapy.

RESULTS

Of the 335 patients included in the analysis, 245 were men (73%); mean (SD) age was 59.4 (13.5) years. Seventy-two eligible patients (18%) were not able to tolerate sacubitril/valsartan, 100 mg/d, during the short run-in period, and 49 patients (29%) discontinued sacubitril/valsartan during the 24 weeks of the trial. The median NT-proBNP AUC for the valsartan treatment arm (n = 168) was 1.19 (IQR, 0.91-1.64), whereas the AUC for the sacubitril/valsartan treatment arm (n = 167) was 1.08 (IQR, 0.75-1.60). The estimated ratio of change in the NT-proBNP AUC was 0.95 (95% CI 0.84-1.08; P = .45). Compared with valsartan, treatment with sacubitril/valsartan did not improve the clinical composite of number of days alive, out of hospital, and free from heart failure events. Aside from a statistically significant increase in non-life-threatening hyperkalemia in the sacubitril/valsartan arm (28 [17%] vs 15 [9%]; P = .04), there were no observed safety concerns.

CONCLUSIONS AND RELEVANCE

The findings of this trial showed that, in patients with chronic advanced heart failure with a reduced ejection fraction, there was no statistically significant difference between sacubitril/valsartan and valsartan with respect to reducing NT-proBNP levels.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT02816736.

摘要

重要性

由于在该人群中缺乏有限的临床经验，因此实践指南不推荐将沙库巴曲缬沙坦用于纽约心脏协会心功能 IV 级射血分数降低的心力衰竭患者。

目的

比较沙库巴曲缬沙坦与缬沙坦在射血分数降低且近期出现纽约心脏协会心功能 IV 级症状的晚期心力衰竭患者中的治疗效果。

设计、地点和参与者：进行了一项双盲随机临床试验；共纳入 335 例晚期心力衰竭患者。该试验于 2017 年 3 月 2 日开始，由于 COVID-19 风险，于 2020 年 3 月 23 日提前停止。

干预

患者被随机分配接受沙库巴曲缬沙坦（目标剂量，每日两次 200 mg）或缬沙坦（目标剂量，每日两次 160 mg）联合推荐的治疗。

主要结局和测量指标

通过 24 周的治疗，测量基线时 N 端脑利钠肽前体（NT-proBNP）比值的曲线下面积（AUC）。

结果

在纳入分析的 335 例患者中，245 例为男性（73%）；平均（SD）年龄为 59.4（13.5）岁。72 名符合条件的患者（18%）在短期导入期内无法耐受沙库巴曲缬沙坦 100 mg/d，49 名患者（29%）在 24 周的试验期间停止使用沙库巴曲缬沙坦。缬沙坦治疗组（n=168）的中位 NT-proBNP AUC 为 1.19（IQR，0.91-1.64），而沙库巴曲缬沙坦治疗组（n=167）的 AUC 为 1.08（IQR，0.75-1.60）。NT-proBNP AUC 变化的估计比值为 0.95（95%CI，0.84-1.08；P=0.45）。与缬沙坦相比，沙库巴曲缬沙坦治疗并未改善患者的临床复合指标，包括存活天数、院外天数和心力衰竭事件无复发天数。除沙库巴曲缬沙坦组非致命性高钾血症发生率有统计学意义的增加（28 [17%] 比 15 [9%]；P=0.04）外，未观察到安全性问题。