沙库巴曲缬沙坦治疗左心疾病相关性肺动脉高压的临床研究

doi:10.12092/j.issn.1009-2501.2019.01.010

中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (1): 57-62.doi: 10.12092/j.issn.1009-2501.2019.01.010

沙库巴曲缬沙坦治疗左心疾病相关性肺动脉高压的临床研究

魏子寒，李栋博，元峥，陆颍，杨国杰

郑州大学第一附属医院老年心血管科，郑州 450052，河南

收稿日期:2018-08-09 修回日期:2019-01-07 出版日期:2019-01-26 发布日期:2019-01-25
通讯作者: 杨国杰，男，博士生导师，教授，主任医师，研究方向：心血管疾病。 Tel:0371-66295162 E-mail：yang63315@126.com
作者简介:魏子寒，女，硕士，主治医师，研究方向：心力衰竭疾病。 Tel:0371-66295162 E-mail：wzhfwyyjx@qq.com
基金资助:
河南省科技攻关计划项目（182102310639）

Clinical trial of sacubitril/valsartan in the treatment of Pulmonary hypertension (PH) due to left heart disease (LHD)

WEI Zihan,LI Dongbo，YUAN Zheng,LU Ying, YANG Guojie

Department of Geriatrics Cardiology, First Affiliated Hospital of Zhengzhou University, Zhengzhou 450000，Henan, China

Received:2018-08-09 Revised:2019-01-07 Online:2019-01-26 Published:2019-01-25

摘要/Abstract

摘要：

目的: 观察沙库巴曲缬沙坦对左心疾病相关性肺动脉高压（PH-LHD）患者的临床症状及血浆内皮素-1（ET-1）和血清可溶性细胞间粘附因子-1（sICAM-1）及人可溶性CD40配体（sCD40L）水平的影响，探讨沙库巴曲缬沙坦治疗PH-LHD的临床疗效及机制。方法: 选取60例心力衰竭合并肺动脉高压的患者随机分为对照组和观察组，每组30例。对照组在一般治疗（吸氧、利尿、扩血管）的基础上给予缬沙坦80 mg，1次/d。观察组在一般治疗的基础上，加用50 mg沙库巴曲缬沙坦，2次/d持续口服。比较两组患者治疗前和治疗90 d的6 min步行距离（6MWD）、肺动脉高压功能分级以及通过超声心动图检测左室舒张末内径（LVEDD）、右室舒张末内径（RVEDD）、左房内径（LAD）、三尖瓣反流速率（TRV）、左心室射血分数(LVEF)、肺动脉收缩压（PASP）。用酶联免疫吸附法测定治疗前和治疗后90 d的血浆N末端前脑钠肽（NT-proBNP）、ET-1及血清sICAM-1、sCD40L的水平。结果: 治疗后，两组患者肺动脉高压功能分级均优于治疗前，观察组差异具有统计学意义（P<0.05），对照组差异无统计学意义（P>0.05）；两组患者6 min步行距离、心脏彩超相关指标均优于治疗前，差异具有统计学意义（P<0.05），血浆NT-proBNP和ET-1及血清sICAM-1和sCD40L水平较治疗前降低，差异具有统计学意义（P<0.05）；与对照组相比，观察组的6 min步行距离的差值、肺动脉高压功能分级、心脏彩超相关指标改善更加显著，血浆NT-proBNP和ET-1及血清sICAM-1和sCD40L水平降低的程度更加明显，差异具有统计学意义（P<0.05）。结论: 沙库巴曲缬沙坦可以更加有效地降低左心衰患者的肺动脉收缩压以及血ET-1、sICAM-1和sCD40L的水平，缓解临床症状，改善预后。

关键词: 心力衰竭, 充血性, 高血压, 肺性, 沙库巴曲缬沙坦

Abstract:

AIM: To observe the clinical efficacy of sacubitril/valsartan in patients with pulmonary hypertension due to left heart disease (PH-LHD) as well as investigate the mechanism of it. METHODS: A total of 60 patients including 35 males and 25 females with PH-LHD were randomly divided into control group（n=30 cases）and observation group（n=30 cases）. Observation group was treated with sacubitril/valsartan by 50 mg twice daily and control group with valsartan by 80 mg daily on the basis of routine treatment. The world health organization functional class (WHO-FC), 6-minute walking distance (6MWD) were compared before and 90 days after treatment between the two groups. The plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and endothelin-1(ET-1) as well as the serum level of sICAM-1and sCD40L were measured before and after treatment by ELISA. Concomitantly, left ventricular end diastolic diameter (LVEDD), right ventricular end diastolic diameter (RVEDD), left atrial diameter (LAD), tricuspid regurgitant velocity (TRV), ejection fraction (EF), pulmonary arterial systolic pressure (PASP) were measured before and after treatment by echocardiography. RESULTS: No significant differences of WHO-FC, 6MWD and EF between the two groups prior to administration of sacubitril/valsartan were observed （P=0.371）, whereas the factors monitored above show a remarkable amelioration in observation group compared to the control group after treatment （P<0.05）. In addition, utility of sacubitril/valsartan has shown more efficacy on the blood levels of NT-proBNP, ET-1, sICAM-1, sCD40L and LVEDD,RVEDD,LAD,TRV,EF and PASP in observation group. CONCLUSION: Sacubitril/valsartan can effectively reduce PASP as well as blood levels of ET-1,sICAM-1 and sCD40L in patients with pulmonary hypertension due to left heart disease，improve the cardiac function and prognosis, relieve the clinical symptoms with relatively high safety.

Key words: heart failure, congestive, hypertension, pulmonary, sacubitril/valsartan

中图分类号:

R544.1

魏子寒，李栋博，元峥，陆颍，杨国杰. 沙库巴曲缬沙坦治疗左心疾病相关性肺动脉高压的临床研究[J]. 中国临床药理学与治疗学, 2019, 24(1): 57-62.

WEI Zihan,LI Dongbo，YUAN Zheng,LU Ying, YANG Guojie. Clinical trial of sacubitril/valsartan in the treatment of Pulmonary hypertension (PH) due to left heart disease (LHD)[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(1): 57-62.

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沙库巴曲缬沙坦治疗左心疾病相关性肺动脉高压的临床研究

Clinical trial of sacubitril/valsartan in the treatment of Pulmonary hypertension (PH) due to left heart disease (LHD)

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