Efficacy And Safety Of Sacubitril/Valsartan In The Treatment Of Heart Failure With Preserved Ejection Fraction: A Meta-analysis

Objective: To systematically evaluate the efficacy and safety of sacubitril/valsartan in the treatment of heart failure with preserved ejection fraction.Methods: Pub Med,Embase,The Cochrane Library(Issue 12,2020),CNKI,Wan Fang Data,VIP and CBM were searched from the establishment of the database to December 31,2020 for randomized controlled trials on the efficacy and safety of sacubitril/valsartan for HFp EF patients.References of included studies were also retrieved,and the unpublished but reliable grey literature was searched through the Internet to supplement the relevant literature.Two researchers independently screened literature according to the inclusion and exclusion criteria,extracted data,assessed the risk of bias of included studies,and cross check.Then,meta-analysis was performed using Rev Man5.4 software.Results: 8 studies were included synthetically in the present meta-analysis,enrolling5561 patients.The results of meta-analysis showed that,compared with the control group,the sacubitril/valsartan group had significant improvements in NYHA classes[RR = 1.21,95%CI(1.09,1.34),P = 0.0002] and 6-minute walk distance [MD =53.71,95%CI(27.43,79.99),P < 0.0001].In addition,compared with the control group,sacubitril/valsartan can reduced MLHFQ score [MD =-10.74,95%CI(-19.97,-1.51),P = 0.02] and significantly decrease the serum NT-pro BNP levels [MD =-299.37,95%CI(-420.87,-177.88),P < 0.00001].There was no significant difference in S/V in all-cause death [RR = 0.96,95%CI(0.84,1.10),P = 0.54] and cardiovascular mortality [RR = 0.94,95%CI(0.79,1.13),P = 0.51] between the S/V group and control group.S/V decreased the rate of rehospitalization due to heart failure [RR =0.85,95%CI(0.56,0.98),P = 0.03] and the incidence of major adverse cardiovascular events [RR = 0.60,95%CI(0.40,0.90),P = 0.01].In terms of echocardiography parameters,S/V can increase E/A ratio [RR = 0.11,95%CI(0.00,0.21),P = 0.04],reduce LVEDD [RR =-3.07,95%CI(-5.98,-0.17),P = 0.04].There was no statistically significant difference in LVEF [MD = 0.28,95%CI(-0.32,0.88),P = 0.36]and LVESD [RR =-5.87,95%CI(-12.80,1.06),P = 0.10] between two groups.In terms of safety,there was no statistically significant difference in the incidence of S/V total adverse reactions [RR = 1.00,95%CI(0.94,1.07),P = 0.98],hyperkalemia [RD=-0.02,95%CI(-0.04,0.00),P = 0.07],dry cough [RR = 0.40,95%CI(0.08,2.03),P = 0.27].S/V reduced the risk of renal insufficiency [RD = 0.50,95%CI(0.34,0.75),P = 0.0007].However,S/V increased the risk of hypotension [RR =1.437u95%CI(1.24,1.64),P < 0.00001] and angioedema [RD = 0.00,95%CI(0.00,0.01),P = 0.01].Conclusion: S/V significantly can improve NYHA classes and 6WMD,reduce MLHFQ score and serum NT-pro BNP levels,and also decrease heart failure-related rehospitalization rates and major cardiovascular adverse events in patients with HFp EF.In terms of echocardiography parameters,S/V can increase E/A ratio and reduce LVEDD.In terms of safety,S/V shows good safety and can reduce the risk of renal insufficiency,but increase the incidence of hypotension and angioedema.Due to limited quality and quantity of the included studies,more high-quality studies are required to verify above conclusions.