Effects Of Sacubitril/Valsartan On Ventricular Remodeling In Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction

Background: The role of sacubitril/valsartan in patients with chronic heart failure(HF)is established.However,the effects on ventricular remodeling in patients with left ventricular systolic dysfunction after acute myocardial infarction is not clear.Objective: Compare the effects and safety of sacubitril/valsartan versus conventional angiotensin converting enzyme inhibitor or angiotensin receptor blocker(ACEI/ARB)on left ventricular(LV)remodeling in patients with LV systolic dysfunction following new onset of spontaneous acute myocardial infarction(AMI).Methods: The study is a single center,prospective cohort,exploratory clinical trial.New onset of spontaneous AMI patients presenting with LVEF < 45% who were treated with Sacubitril/Valsartan or ACEI/ARB were continuously enrolled.All patients underwent successful revascularization.They were divided into ARNI group and ACEI/ARB group according to the medication situation.The changes of echocardiographic parameters and plasma biochemical markers were used to evaluate the effects of sacubitril/valsartan on LV remodeling and cardiac function.The primary end point is cardiac reverse remodeling(CRR)index and the effect of drug dose on CRR at 6-month post-infarct,The CRR index included left ventricular ejection fraction(LVEF),left ventricular end diastolic diameter(LVEDD),left atrial end systolic diameter(LAESD),changes from baseline to 6-month,LVEF returned to normal(LVEF> 50%),LVEF improvement ≥ 10%,and the proportion of LVEDD deterioration.The secondary end points is the incidence of HF readmission and major adverse cardiac events(MACEs)at 6 months of follow-up.MACEs are defined as the composite end points of cardiac death,myocardial infarction(MI)and HF hospitalization.The safety evaluation indexes were deterioration of renal function,hyperkalemia,symptomatic hypotension and angioneurogenic edema.Results: 1.Baseline:From December 2018 to August 2020,a total population of96 eligible patients were enrolled.The mean age was 63.11 ± 12.42,77.1% men,68.8%presented with STEMI,92.4% STEMI patients visited the doctor within 24 hours.Baseline clinical and echocardiographic characteristics were comparable between groups.2.Main effificacy endpoint:(1)At 6 months,LVEDD and LAESD in ARNI group decreased by 2.5mm(± 5.35,P =0.002)and 1.4mm(± 3.40,P =0.007)compared with baseline,but there was no significant change in ACEI/ARB group;LVEF in both groups increased significantly compared with baseline,but the change was more prominent in the ARNI group(10.5 %(4.00,16.00)vs.5.5%(1.75,12.00),P=0.024).(2)There was no significant difference on LVEDD and LAESD between groups at 6months,but LVEDD in ARNI group showed a downward trend(P =0.088),and the degree of deterioration was much lower than ACEI/ARB group(2.1% vs.14%,P <0.05).The percentage of patients with increased LVEF ≥ 10% in ARNI group was 52%,significantly higher than 30.4% in ACEI / ARB group(P =0.032);the percentage of patients with normal LVEF in ARNI group was also significantly higher than ACEI/ARB group(40.0% vs.19.6%,P =0.029).(3)The ARNI group was divided into three subgroups: group A(≤ 50mg/d),group B(50-100mg/d)and group C(> 100mg/d)according to the drug dose at 6 months.1)The LVEF between subgroups was similar at baseline.During the 6-month follow-up,2)the LVEF of each group was improved compared with the baseline,but there was no significant difference in group A(P >0.05).3)there were significant differences in LVEF and△ LVEF among the three groups(P=0.000),and group C > group B > group A.4)pairwise comparison among the three groups: there was no difference between group A and group B,but there were significant differences between group A and group C,group B and group C(P < 0.01).(4)BNP concentration in both groups decreased significantly compared with baseline(all P< 0.05),but there was no significant difference between groups at 6 months.3.Secondary endpoint: Compared with ACEI/ARB group,although the incidence of MACEs and HF hospitalization in ARNI group was lower(8% vs.15.2%;OR: 0.526,95% CI 0.165-1.679,P = 0.267)and(6% vs.13%,P =0.304),there was no significant difference between groups.4.Safety: The incidence of symptomatic hypotension was higher in ARNI group(12% vs.4.3%,P =0.271),but there was no significant difference.No difference in other safety clinical endpoints such as deterioration of renal function,hyperkalemia and angioneurogenic edema was observed.Conclusion: 1.Early initiation of sacubitril/valsartan can improving systolic function and attenuating adverse cardiac remodeling,which is superior over ACEI/ARB in patients with LV systolic dysfunction after AMI.2.ARNI has a dose-dependent effect on cardiac reverse remodeling,even if it does not reach the target dose,it can significantly improve LVEF,and the higher medicine dose,the better improvement effect.3.There was no difference in secondary endpoint and safety between groups.