注射用重组人脑利钠肽联合沙库巴曲缬沙坦钠治疗HFrEF患者的临床研究

Clinical trial of recombinant human brain natriuretic peptide combined with sacubitril valsartan sodium in the treatment of patients with HFrEF

目的观察注射用重组人脑利钠肽(rhBNP)联合沙库巴曲缬沙坦钠治疗射血分数下降心力衰竭(HFrEF)的疗效及对患者心功能指标、心率变异性、自主神经功能的影响。方法将HFrEF患者按照治疗方式分为对照组和试验组。对照组给予沙库巴曲缬沙坦钠片,每次50 mg,每天2次,口服,治疗30 d。试验组在对照组的基础上给予rhBNP 1.5μg·kg^(-1),静脉注射,后以0.75×10^(-2)μg·kg^(-1)·min^(-1)持续静脉泵入3 d。比较2组患者的心率变异性及自主神经功能指标[24 h正常窦性R-R间期标准差(SDNN)、窦性心搏间期标准差均值(SDNNI)、正常相邻R-R间期差值的均方根(rMMSD)、窦性心搏间期差值大于50 ms的百分比(pNN50)]、临床疗效、心功能指标[左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心室射血分数(LVEF)、N-末端B型脑钠肽前体(NT-proBNP)、血管紧张素转换酶2(ACE2)、心肌肌钙蛋白Ⅰ(cTnⅠ)],以及药物不良反应的发生情况。结果对照组和试验组分别纳入53例和42例。治疗后,试验组的治疗总有效率为95.24%,高于对照组的81.13%(P<0.05)。治疗后,试验组和对照组的rMMSD分别为(34.19±4.05)和(30.86±3.75)ms,SDNN分别为(93.28±4.59)和(88.32±4.38)ms,SDNNI分别为(42.63±4.65)和(37.52±4.28)ms,LVESD分别为(34.28±3.86)和(40.39±4.19)mm,LVEF分别为(47.35±4.81)%和(41.64±4.53)%,NT-proBNP分别为(1154.63±197.75)和(1454.17±201.49)ng·L^(-1),ACE2分别为(24.59±3.12)和(21.36±2.93)U·L^(-1),cTnⅠ分别为(0.12±0.03)和(0.15±0.04)μg·L^(-1),差异均有统计学意义(均P<0.05)。试验组和对照组的药物不良反应有恶心呕吐、头晕、低血压、心悸等,试验组和对照组的药物不良反应发生率分别为19.05%和13.21%,差异无统计学意义(P>0.05)。结论rhBNP联合沙库巴曲缬沙坦钠应用于HFrEF患者治疗中可调节心率变异性,改善其自主神经功能及心功能,提高治疗效果。

Objective To observe the efficacy of recombinant human brain natriuretic peptide for injection(rhBNP)combined with sacubitril valsartan sodium in the treatment of heart failure with reduced ejection fraction(HFrEF)and its influence on cardiac function indicators,heart rate variability and autonomic nervous function.Methods Patients with HFrEF were divided into control group and treatment group according to the treatment methods.Control group was treated with sacubitril valsartan sodium orally(50 mg a time,bid)for 30 days,and treatment group was additionally given rhBNP on the basis of control group[intravenous injection of 1.5μg·kg^(-1),and then continuous intravenous pump at a rate of 0.75×10^(-2)μg·kg^(-1)·min^(-1)for 3 days].The heart rate variability and autonomic nervous function indicators[standard deviation of the normal RR intervals(SDNN),mean standard deviation of sinus interval(SDNNI),root mean square of differences in successive RR intervals(rMMSD),percentage of sinus cardiac interval greater than 50 ms(p NN50)],clinical efficacy,cardiac function indicators[left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),N-terminal pro-brain natriuretic peptide(NT-proBNP),angiotensin-converting enzyme 2(ACE2),cardiac troponinⅠ(cTnⅠ)]and occurrence of adverse drug reactions were compared between both groups of patients.Results There were 53 cases in control group and 42 cases in treatment group were finally enrolled.After treatment,the total effective rate in treatment group was95.24%,higher than 81.13%in control group(P<0.05).After treatment,rM MSD values in treatment group and control group were(34.19±4.05)and(30.86±3.75)ms;SDNN values were(93.28±4.59)and(88.32±4.38)ms;SDNNI values were(42.63±4.65)and(37.52±4.28)ms;LVESD values were(34.28±3.86)and(40.39±4.19)mm;LVEF values were(47.35±4.81)%and(41.64±4.53)%;NT-proBNP levels were(1154.63±197.75)and(1454.17±201.49)ng·L^(-1);ACE2 levels were(24.59±3.12)and(21.36±2.93)U·L^(-1);cTnⅠlevels were(0.12±0.03)and(0.15±0.04)μg·L^(-1);the difference were all statistically significant(all P<0.05).The adverse drug reactions in treatment group and control group were nausea and vomiting,dizziness,hypotension and palpitation,the total incidence of adverse drug reactions in treatment group and control group were 19.05%and 13.21%respectively(P>0.05).Conclusion rhBNP combined with sacubitril valsartan sodium can regulate the heart rate variability,improve the autonomic nervous function and cardiac function and enhance the therapeutic effect in patients with HFrEF.