Efficacy Of Sacubitril-valsartan In Heart Failure Patients With Low Systolic Blood Pressure And Baseline Factors For Elevated Systolic Blood Pressure After Treatment

Background and Objective:Heart failure(HF)has become a major global health problem with high morbidity and mortality.Low systolic blood pressure(LSBP)is an important factor limiting the use or up-titration of drugs that inhibit myocardial remodeling in patients with HF.Sacubitril-valsartan,an angiotensin receptor neprilysin inhibitor,has been shown that low-dose sacubitril-valsartan benefits heart failure with reduced ejection fraction(HFr EF)patients with lower blood pressure and is comparable to that in patients with higher blood pressure.SBP is increased in patients with the lowest baseline SBP(<110mm Hg)after treatment with sacubitril-valsartan.However,the HF patients in the RCT study only included patients with SBP>100-110 mm Hg.The study shows that the rate of sacubitril-valsartan in discharged HF patients with SBP<95mm Hg is 35.5%,and 45.6% in HFr EF patients in China.This suggests that many HF patients with LSBP(SBP≤105mm Hg)are trying to receive sacubitrilvalsartan in clinical practice,but there is no relevant research report on the comparison of its efficacy with non-LSBP HF patients.Therefore,this study will compare the differences in baseline characteristics of HF patients with LSBP and non-LSBP treated with sacubitril-valsartan firstly,then analyze the efficacy of sacubitril-valsartan in HF patients with LSBP after being treated for about 32 weeks and compare the efficacy with HF patients without LSBP.Finally,we explore the baseline factors that may predict significantly higher SBP after treatment in HF patients with LSBP.Methods:This study retrospectively collected patients diagnosed with HF in the second affiliated hospital of Nanchang University from November 2017 to November 2020 and treated them with sacubitril-valsartan.Cases were screened according to the inclusion and exclusion criteria.All patients were divided into two groups by using SBP=105mm Hg.HF patients with baseline SBP≤105mm Hg were defined as heart failure with low systolic blood pressure(HF-LSBP),and baseline SBP>105mm Hg were defined as heart failure with no low systolic blood pressure(HF-NLSBP).Then the baseline data and follow-up data after being treated for about 32 weeks were collected separately.The main data were as follows.General information(gender,age,blood pressure,etc.),HF-related indicators(NYHA classification,etiology of HF),Concomitant diseases and medications,Blood biochemical indicators(renal function,electrolytes,NT-pro BNP,etc.),Echocardiography relevant indicators and Adverse events(hypotension discontinuation,renal failure,all-cause death).The echocardiography-related indicators: right atrium dimension(RAD),right ventricle diameter(RVD),left atrium dimension(LAD),left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic dimension(LVEDD),pulmonary artery diameter(PAD),left ventricular ejection fraction(LVEF).This study was completed through the following steps.Firstly,the differences in baseline characteristics of the two groups of patients were compared and analyzed.Secondly,changes in blood pressure,NYHA cardiac function,N-pro BNP and cardiac structure parameters in the two groups after treatment with sacubitril-valsartan were analysed,and the difference in efficacy between the two groups was compared.Finally,we analyzed whether the SBP was significantly increased(≥9 mm Hg)in the HF-LSBP group after treatment,and explored the baseline characteristics that have predictive value for the significantly increased SBP in HF-LSBP patients after treatment.Results:1.This study included a total of 701 HF patients treated with sacubitril-valsartan.245 cases with an average age of 62.6±15.9years and 70.6% of males in the HFLSBP group,and 456 cases with an average age of 66.0±15.6years and 69.3% of males in the HF-NLSBP group.The baseline SBP was 99(93-102)mm Hg in patients in the HF-LSBP group and 126(115-138)mm Hg in the HF-NLSBP group.Compared with the HF-NLSBP group,the patients in the HF-LSBP group were younger,had a smaller body mass index(BMI),had a lower prevalence of hypertension and coronary heart disease,and higher prevalence of atrial fibrillation and ventricular tachycardia(all P<0.01).In terms of etiology,patients in the HF-LSBP group were more likely caused by dilated cardiomyopathy(64.9%),but less likely caused by hypertensive and ischaemic origin(both P<0.05).Patients in the HF-LSBP group had a higher NYHA cardiac functional class(P<0.0001).Patients in the HF-LSBP group had significantly lower initial doses of sacubitril-valsartan,and the percentage of mineralocorticoid receptor antagonist(MRA),inotropes,diuretics,and anticoagulant drugs was higher(all P<0.0001).Patients in the HF-LSBP group had lower levels of total cholesterol(TC),triglycerides(TG),serum sodium and chloride(all P<0.01).While the NT-pro BNP level was significantly higher in the HF-LSBP group(P=0.0001).In terms of echocardiography,and the RAD,RVD,LAD,LVESD,LVEDD and PAD in the HF-LSBP group were larger(all P<0.01),and the LVEF was smaller(P<0.0001).2.After the screening,a total of 449 HF patients with relatively complete followup data and continuous use of sacubitril-valsartan were included.There were 167 patients in the HF-LSBP group and 282 patients in the HF-NLSBP group.14 patients in each group experienced adverse events and discontinued medication.14.4% of patients in the HF-LSBP group and 25.4% of patients in the HF-NLSBP group had achieved the target dose of sacubitril-valsartan finally.Comparison between before and after treatment of the two groups: NYHA cardiac function was improved,and NT-pro BNP was significantly decreased(all P<0.0001).The LAD,LVESD and LVEDD were significantly decreased,and LVEF was significantly increased in both groups after treatment(all P<0.0001).PAD was decreased in both groups(P values were 0.002 and 0.0198,respectively).Serum potassium increased by 0.13 mmol/l(P=0.0056)in the HF-LSBP group after treatment,and e GFR in the HF-NLSBP group was mildly decreased after treatment(P=0.0357).Comparison of the efficacy between the two groups: adjusted for baseline,the LVEF in the HF-NLSBP group increased significantly,and the LVEDD decreased more significantly(all P<0.05).SBP in the HF-LSBP group increased by 9.79 mm Hg after treatment,while decreased by 10.40 mm Hg in the HF-NLSBP group.There were no significant differences in other indicators between the two groups.The patients in the HF-LSBP group had a significantly higher withdrawal rate due to hypotension than the HF-NLSBP group after medication(6.0% vs 1.1%,P=0.006).There was no significant difference in the rate of renal failure and all-cause mortality between the two groups.3.In HF-LSBP patients after treatment with sacubitril-valsartan for 32 weeks,72 patients had significantly increased in SBP,and 81 patients had no significant increase.Compared with the group with no significant increase in SBP,the group with significantly increased SBP had a lower baseline SBP of about 3 mm Hg(P=0.0329);the proportion of history of hypertension was higher(P<0.001);NYHA classification was lower with mainly grade II/III(P=0.002);the use rate of MRA was lower(P= 0.026),and calcium antagonist was higher(P=0.032).In terms of blood biochemistry and cardiac structure,compared with the group with no significant increase in SBP,the group with significantly increased SBP had higher blood chloride(P=0.003);PAD was smaller(P=0.0145),and LVEF was higher in 4%(P=0.0079),the proportion of HFr EF was lower(P=0.046).Under univariate and multivariate Logistic regression analysis,the history of hypertension,NYHA class,blood chloride and LDL had important effects on the significant changes in SBP after treatment(all P<0.05).Further research found that the Logistic regression model constructed by baseline SBP,history of hypertension,NYHA class,blood chloride and LDL had good judgment ability and clinical effect in predicting the significant increase in SBP after treatment.Conclusions:(1)Compared with the HF-NLSBP group,the HF-LSBP patients were characterized as younger,lower BMI,worse NYHA cardiac function,more severe cardiac structural damage,a higher proportion of arrhythmia,lower blood sodium and blood chloride,and a high percentage of MRA,diuretics and inotropes.(2)The level of NT-pro BNP was decreased,and NYHA cardiac function and cardiac structure were significantly improved after treatment with sacubitril-valsartan in both the HF-LSBP group and HF-NLSBP group,but the benefit of cardiac structure in HF-LSBP group was inferior to the HF-NLSBP group.A higher rate of discontinuation due to hypotension occurred in the HF-LSBP group,while SBP was increased for the HF-LSBP patients who tolerated sacubitril-valsartan.(3)The prediction model based on baseline SBP,history of hypertension,NYHA cardiac function class,blood LDL and blood chloride has good judgment ability and clinical effect on the significant increase of SBP in HF-LSBP patients treated with sacubitril-valsartan.