Analyzation Of The Application Status Of Sacubitril/Valsartan Sodium In Patients With Whole-range Ejection Fraction Heart Failure

Objective:Sacubitril/valsartan sodium,a new class of angiotensin receptor neprilpeptidase inhibitor(ARNI),has been approved for the treatment of patients with whole-range ejection fraction heart failure.However,the application of sacubitril/valsartan sodium in the treatment of whole-range ejection fraction heart failure in the real world is not clear,and the clinical application data are relatively insufficient.There are differences between the population treated with sacubitril/valsartan sodium in the real world and the population enrolled in clinical research.The application status and existing problems of sacubitril/valsartan sodium in patients with different types of heart failure with ejection fraction in China are still unclear.Therefore,this study will analyze the application status of sacubitril/valsartan sodium in a single center to provide reference for its application in Chinese people with different ejection fractions.Methods:This study was an observational,single-center real-world study.A total of 130 patients with chronic heart failure who were prescribed sacubitril/valsartan sodium in Shengjing Hospital of China Medical University from December 2019 to October 2021 were enrolled.Heart failure with reduced ejection fraction(HFrEF),heart failure with mid-range ejection fraction(HFmrEF),and heart failure with preserved ejection fraction(HFpEF)were classified according to left ventricular ejection fraction.The basic data,laboratory examination,ultrasonic cardiac structure and function,treatment plan,initial application of sacubitril/valsartan sodium,dose compliance after 3 months of follow-up,and adverse events during 3 months of follow-up were compared between the groups,and the related factors affecting the dose compliance of sacubitril/valsartan sodium were analyzed.Results:1.Comparison of baseline data among the three groupsPatients in HFpEF group were older[(65.0±13.54)years old vs(59.8±15.33)years old vs(53.4±16.23)years old,P=0.002]and less male(44.4%vs 64.7%vs 73.3%,P=0.002)than patients in HFmrEF group and HFrEF group.P=0.017),slower basal heart rate[69.0(59.00,78.00)beats/min vs 80.0(71.00,92.75)beats/min vs 80.0(70.00,98.00)beats/min,P<0.001],NYHA class Ⅳ(3.1%vs 41.2%vs 43.3%,P=0.003),hypertension(72.2%vs 58.8%vs 46.7%;P=0.048)and atrial fibrillation(38.9%vs 29.4%vs 15.0%,P=0.028).Compared with patients with HFmrEF and HFpEF,patients with HFrEF had more dilated cardiomyopathy(53.3%vs 26.5%vs 2.8%,P<0.001).Echocardiographic data showed that HFrEF group had a larger left ventricular end-systolic volume than HFmrEF group and HFpEF group[(154.7±65.46)ml vs(96.1±38.58)ml vs(45.9±21.19)ml,P<0.001],left ventricular enddiastolic volume[(223.5±83.37)ml vs(171.2±67.28)ml vs(111.6±41.76)ml,P<0.001]and left ventricular diameter[(66.5±9.24)mm vs(58.3±9.90)mm vs(49.3±4.72)mm,P<0.001].In terms of baseline biochemical indicators,HFrEF group has higher NTproBNP[3626.0(1756.00,7007.00)pg/mL vs 3607.0(1535.75,6949.00)pg/mL vs 1827.0(718.10,3280.00)pg/mL;P=0.003],hs-TNT[0.06(0.030,0.373)ng/mL vs 0.03(0.017,0.253)ng/mL vs 0.04(0.013,0.680)ng/mL;P=0.012],T-BIL[15.6(8.70,29.10)μmol/L vs 10.4(7.08,18.28)μmol/L vs 9.3(6.20,14.40)μmol/L,P=0.001],and D-BIL[5.1(3.30,11.80)μmol/L vs 3.9(2.48,6.03)μmol/L vs 3.4(2.60,6.10)μmol/L,P=0.009].HFpEF group had lower RBC relative to HFmrEF group and HFrEF group[(4.00+0.720)x 1012/L vs(4.22+0.901)x 1012/L vs(4.73+0.787)x 1012/L,P<0.001],Hb[(123.8±24.02)g/L vs(129.1±26.07)g/L vs(142.9 ±22.04)g/L,P<0.001],and higher hsCRP[19.6(19.55,36.41)mg/L vs 15.5(13.83,18.15)mg/L vs 11.1(11.05,12.36)mg/L,P<0.001].In terms of guidelinedirected treatment,HFpEF group had a higher proportion of SGLT-2i application(13.9%vs 8.8%vs 1.7%,P=0.045).2.Drug use of sacubitril/valsartan sodiumIn this study,36.2%patients achieved the target dose of sacubitril/valsartan sodium.The average starting dose of sacubitril/valsartan sodium was[133.33±59.244)mg/d vs(122.06±56.664)mg/d vs(127.08±63.633)mg/d.P=0.648],and the average tolerated dose was[(279.58±124.064)mg/d vs(252.94±114.773)mg/d vs(247.22±126.460)mg/d;P=0.350]and the proportion of achieving the target dose(43.3%vs 26.5%vs 33.3%,P=0.241).3.Safety data of sacubitril/valsartan sodiumCompared with the baseline level,the systolic blood pressure(SBP)of patients with global ejection fraction heart failure after follow-up was[121.5(109.75,135.00)mmHg vs 113.7(101.75,130.00)mmHg,P<0.001]and diastolic blood pressure[73.0(65.00,81.50)mmHg vs 69.8(62.00,77.25)mmHg,P<0.001]were significantly lower than those at baseline,and eGFR was higher than that at baseline[(70.1±30.54)mL/min/1.73m^2 vs(75.9±29.28)mL/min/1.73m△2,P<0.001].There was no significant difference in K+level before and after follow-up.Hypotension occurred in 35.4%of HFpEF patients during the follow-up period,but there was no significant difference in the incidence of adverse events among HFrEF,HFmrEF and HFpef patients.4.To analyze the related factors affecting the dosage target achievement of sacubitril/valsartan sodium.In this study,the risk factors for achieving the target dose of sacubitril/valsartan sodium in heart failure patients with global ejection fraction included the starting dose(OR 1.013;95%CI 1.006-1.020,P<0.001)and baseline systolic blood pressure level(OR 1.019;95%CI 1.000-1.039,P=0.048).Conclusion:In the real-world study of our center,sacubitril/valsartan sodium was used in patients with chronic heart failure with different ejection fraction types.There was no significant difference in the initial dose,average tolerated dose and target dose among the three groups,indicating that there was no significant difference in the tolerance of sacubitril/valsartan sodium in patients with heart failure with different ejection fraction types.However,the overall target dose compliance is not ideal.The starting dose and baseline systolic blood pressure are the main factors affecting the dose compliance.In our real-world study,sacubitril/valsartan sodium use in patients with chronic heart failure and different ejection fraction types has a relatively common adverse effect of hypotension,which does not affect the dose compliance at 3 months.Therefore,trying titration is the key solution to improve the compliance rate.In our study,the increase in eGFR after the follow-up period suggests that sacubitril/valsartan sodium has a renoprotective effect in patients with chronic heart failure with all ejection fractions.