ARNI Versus ACEI Or ARB For Short-term Prognosis In Patients With CTO-PCI With Low Ejection Fraction

Objective:Chronic coronary artery occlusion(Chronic total coronary artery occlusion,CTO)is usually secondary to atherosclerotic plaque,the CTO patients directly to the skin of coronary artery interventional therapy(percutaneous coronary intervention,The mortality rate after PCI remains high.In recent years,with the progress of myocardial reperfusion and endovascular imaging,as well as the breakthrough of treatment programs such as secondary prophylactic drugs for coronary heart disease,the treatment of patients with coronary atherosclerotic heart has been optimized.However,the high mortality rate of patients after CTO-PCI has been a problem for many clinicians.How to prolong the life span of patients with low ejection fraction after successful CTO-PCI is an important problem to be solved.Enkephalin/angiotensin receptor antagonists as a combination of the RAAS system and the natriuretic peptide system have shown remarkable efficacy in changing ejection fraction in patients with heart failure.This study aimed to investigate whether ARNI could improve the prognosis of patients with successfully treated CTO with drugeluting stents and reduced ejection fraction more than traditional ACEI/ARB.Methods:In this study,CTO patients who received drug-eluting stent implantation in Jiangxi Provincial People’s Hospital from December 1,2018 to December 1,2020 were selected.After PCI,the occlusive blood vessels were recanalized successfully,and the left ventricular ejection fraction was lower than 40%,who had no history of angiotensin-converting enzyme inhibitors or arb tolerance,symptomatic hypotension or systolic blood pressure <100mm Hg at screening,estimated glomerular filtration rate(e GFR)<30m L/min/1.73m2,blood potassium concentration > 5.5mmol/L,and history of angioedema.ARNI or ACEI/ARB were divided into ARNI group and ACEI/ARB group.In case of alternating use of ACEI/ARB and ARNI,it should be defined as ARNI group that people who start to use ARNI after 72 hours of discontinuation of ACEI.Eighty-seven patients(30.4%)were included in the ARNI group who received Shakubactril valsartan sodium tablets after CTO-PCI.One hundred ninety-nine patients(69.6%)were enrolled in the ACEI/ARB group using angiotensin converting enzyme inhibitors(ACEI)or angiotensin II receptor antagonists(ARBs)after CTO-PCI.Trained professionals followed up the enrolled population by telephone.The primary endpoint event was all-cause death,and the secondary endpoint event was improvement in cardiac function(CCS grading).Baseline clinical data and follow-up data of the two groups were collected for data analysis.All data were collected using IBM SPSS27.0(IBM,New York,USA)software.The distribution of baseline data between the two groups was described,and end-point events,including all-cause death and improved cardiac function(CCS scale),were contrasted between the two groups during follow-up to explore whether ARNI was superior to ACEI/ARB in patients with low ejection fraction and CTO PCI.P <0.05 was statistically significant.Result:We enrolled a total of 286 patients with an ejection fraction of less than 40% and successful CTO-PCI.Eighty-seven patients(30.4%)were included in the ARNI group after CTO-PCI using Sacubitril valsartan sodium tablets.One hundred sixty-nine patients(69.6%)were enrolled in the ACEI/ARB group using angiotensin converting enzyme inhibitors(ACEI)or angiotensin II receptor antagonists(ARBs)after CTOPCI.The ARNI group had lower body weight,height and HDL(p values 0.037 and0.028,respectively),but lower albumin,troponin I,direct bilirubin,PT% and HDL(P values 0.004,0.024,0.048,< 0.001 and 0.012,respectively).Compared with the ACEI/ARB group,there were statistically significant differences in the history of atrial fibrillation,PCI history,admission diagnosis,number of coronary artery lesions,PCI route,whether aspirin was used,whether betaloc was taken,and whether aldosterone receptor antagonist was taken(P values were 0.018,0.001,0.02,0.001,0.005,0.016,0.016,0.002,respectively));However,we found age,BMI,systolic blood pressure,diastolic blood pressure,heart rate,CK-MB,white blood cell count,hemoglobin,hematocrit,platelets,potassium concentration,NT-BNP,total bilirubin,alkaline phosphatase,total cholesterol,triglycerides,low density lipoprotein,creatinine,urea nitrogen,uric acid,estimated glomerular filtration rate,and hemoglobin a1 c between the two groups Protein,left ventricular end-diastolic diameter,left ventricular end-systolic diameter,left ventricular ejection fraction,left atrial size,sex,smoking history,hypertension,diabetes,hyperlipidemia,previous CABG,CCS classification of cardiac function at admission,whether there was left main disease,rotatory branch(LCX)occlusion,anterior descending branch(LAD)occlusion,right coronary artery(RCA)occlusion,the use of clopidogrel,ticagrelor or statins,there was no statistically significant difference.The median follow-up period was 24 months.During follow-up,83 patients(29.0%)had all-cause death and 164patients(57.3%)had improved cardiac function grade.Kaplan-Meier method was used to compare short-term major adverse cardiovascular events(including all-cause mortality and graded improvement in cardiac function)between the ARNI group and the ACEI/ARB group after successful CTO-PCI.Differences in the distribution of primary endpoint events(all-cause death)and secondary endpoint events(improvement in CCS grading of cardiac function)were examined by Log rank.The results showed that the all-cause mortality of the primary endpoint event was statistically significant between the ARNI group and the ACEI/ARB group,χ2=30.960,P < 0.001.Kaplan-Meier method was used to compare the therapeutic effect of two groups of drugs on patients with low ejection fraction and successful CTO-PCI.The median survival time of the ARNI group was 38.163 months(95%CI:32.634-39.366),which was longer than that of the ACEI/ARB group(median time:29.957,95%CI: 28.805-35.195).At the same time,there was significant difference in CCS grading between the ARNI group and the ACEI/ARB group after CTO-PCI(χ2=5.960,P=0.017),However,the ARNI group showed less improvement in cardiac function compared to the ACEI/ARB group.Finally,Cox univariate and multivariate analyses were made.Univariate analysis found that treatment style(use of ARNI or ACEI/ARB)was independent of all-cause mortality(P < 0.001).Compared with ARNI,the risk of death was higher in CTO-PCI patients treated with ACEI/ARB,HR=20.699(95%CI:4.749-90.208).Cox multivariate analysis was further performed to determine whether ARNI use was an independent risk factor for all-cause death after successful CTO-PCI with low ejection fraction.After adjusting for traditional secondary prevention of coronary heart disease and potential confounding factors that might influence endpoint events,we found that patients in the ACEI/ARB group had a significantly increased risk of short-term all-cause death after successful CTO-PCI(HR=11.436(95%CI: 3.610-36.230)than those in the ARNI group(P < 0.001).In addition,univariate analysis suggested that CCS grading of cardiac function was improved in both the ARNI group and the ACEI/ARB group after CTO-PCI(p=0.003),but the extent of CCS grading improvement in the ARNI group was lower than that in the ACEI/ARB group(HR=0.650(0.471-0.897).In the multivariable COX regression analysis,after adjusting for secondary preventive drug factors and other statistically significant confounding variables,drug grouping(using ARNI or ACEI/ARB)was independently associated with short-term all-cause death and improved CCS grading of cardiac function after CTO-PCI(P<0.001,0.009,respectively).Therefore,ARNI was more effective than ACEI/ARB in improving allcause death in patients with low ejection fraction and successful CTO-PCI,but the improvement of cardiac function was lower than that in ACEI/ARB group.Conclusion1.The short term risk of all-cause mortality was higher in the group with low ejection fraction and successful CTO-PCI(HR=11.436(95%CI: 3.610-36.230),P <0.001).Therefore,ARNI is more effective than ACEI/ARB in improving all-cause death in people whowith low ejection fraction and successful CTO-PCI.2.Both ARNI and ACEI/ARB could improve cardiac function in patients with low ejection fraction and successful CTO-PCI,but the improvement degree of cardiac function in patients with ARNI was lower than that in the ACEI/ARB group(HR=0.650(95%CI=0.471-0.897),P=0.009).