The Clinical Efficacy And Safety Of LCZ696 In Treatment Of Asian Patients With Essential Hypertension:A Meta-analysis

Objective:A large number of clinical studies have shown that LCZ696 is superior to traditional antihypertensive drugs in the treatment of essential hypertension.According to the epidemiological characteristics that salt-sensitive hypertension is more popular in the Asian patients of essential hypertension,we performed this Meta-analysis to evaluate the clinical efficacy and safety of LCZ696 in treatment of Asian patients with essential hypertension.Methods:We searched the PubMed,Embase,Cochrane library,clinicaltrials.gov,CNKI and wanfang database in accordance with the set retrieval strategies through March 2018.After a preliminary screening and deduplication,we chose literatures and experiments according to inclusion and exclusion criteria strictly,and then confirmed studies for us to initiate research and analysis.Two researchers independently evaluated the quality of included studies using Cochrane System Evaluation Manual 5.1.0 and extracted the data from them.The study data were analysed in RevMan 5.3software,and pooled effect of intervention was measured using standard mean difference(SMD)or relative risk(RR)in combination with 95%confidence interval(CI).The results of Meta analysis were discussed in combination with the epidemiological characteristics of essential hypertension,treatment methods,pharmacology of LCZ696 and related research results,and then we drew the final conclusions.Results:Finally,four randomized controlled trials(RCTs)with 3473patients(2316 cases,1257 controls)were included in this Meta-analysis.Subgroup analysis was performed on each effect index according to the different control drugs,and the dose-effect analysis was performed according to the dose level of LCZ696.The results showed that the rate of successful controlled blood pressure in LCZ696 group was higher than that in olmesartan group and placebo group(RR=1.34,95%CI=1.25~1.43,P<0.00001,I~2=86%),and other efficacy outcome indicators in LCZ696 group were all lower than those in olmesartan group and placebo group,including mean sitting systolic blood pressure(SMD=?8.17,95%CI=?10.07~?6.26,P<0.00001,I~2=99%),mean sitting diastolic blood pressure(SMD=?6.23,95%CI=?7.34~?5.12,P<0.00001,I~2=99%),mean ambulatory systolic blood pressure(SMD=?13.39,95%CI=?16.62~?10.15,P<0.00001,I~2=99%),mean ambulatory diastolic blood pressure(SMD=?10.54,95%CI=?13.14~?7.93,P<0.00001,I~2=99%),mean sitting pulse pressure(SMD=?5.97,95%CI=?7.54~?4.40,P<0.00001,I~2=99%)and mean ambulatory pulse pressure(SMD=?13.31,95%CI=?16.95~?9.67,P<0.00001,I~2=99%).Meanwhile,there was no statistically significant difference between the incidences of adverse events(RR=1.01,95%CI=0.83~1.21,P=0.95,I~2=0%)and serious adverse events(RR=0.89,95%CI=0.33~2.37,P=0.81,I~2=0%)in LCZ696 group and those in olmesartan group or placebo group.To evaluate the dose-effect relationship,LCZ696 400mg group and LCZ696 200mg group had no significant difference in the rate of successful controlled blood pressure(RR=1.07,95%CI=0.98~1.17,P=0.13,I~2=0%),while the rest efficacy outcome indicators were reduced in LCZ696 400mg group obviously compared with LCZ696 200mg group,including mean sitting systolic blood pressure(SMD=?2.31,95%CI=?2.91~?1.71,P<0.00001,I~2=96%),mean sitting diastolic blood pressure(SMD=?2.02,95%CI=?2.55~?1.50,P<0.00001,I~2=95%),mean ambulatory systolic blood pressure(SMD=?2.04,95%CI=?3.41~?0.67,P=0.004,I~2=99%),mean ambulatory diastolic blood pressure(SMD=?1.62,95%CI=?2.68~?0.56,P=0.003,I~2=98%),mean sitting pulse pressure(SMD=?1.55,95%CI=?1.81~?1.30,P<0.00001,I~2=81%)and mean ambulatory pulse pressure(SMD=?2.07,95%CI=?3.82~?0.31,P=0.02,I~2=99%).Simultaneously,there was no statistically significant difference between the incidences of adverse events(RR=1.00,95%CI=0.80~1.25,P=0.99,I~2=0%)and serious adverse events(RR=1.01,95%CI=0.14~7.14,P=0.99,I~2=0%)in LCZ696 400mg group and those in LCZ696 200mg group.Conclusion:In the treatment of essential hypertension in Asian population,the antihypertensive effect of LCZ696 is more significant than olmesartan.LCZ696 400mg is superior to LCZ696 200mg in the effect of most blood pressure indicators and two dose levels are similar in rate of successful controlled blood pressure.Meanwhile,LCZ696 is safe and the safety of 200mg and 400mg is similar with each other.