Meta analysis and trial sequential analysis on Inclisilan in treatment of hypercholesterolemia

Yu Yunfeng; Zhou Manli; Luo Xiaoxin; Jiang Pengfei; Qi Zhengyi; Jian Weixiong

doi:10.3969/j.issn.1674-4055.2023.09.02

Abstract：Objective To review systematically the efficacy and safety of inclisiran in hypercholesterolemia treatment and cardiovascular prognosis.Methods The databases of CBM,CNKI,WanFang Data,VIP Database,PubMed,EMbase,the Cochrane Library and Web of Science were retrieved from database establishment time to Mar.2021.The published randomized controlled trials(RCT)related to hypercholesterolemia treatment with Inclisiran were given a Meta-analysis and trial sequential analysis(TSA).The lipid regulating effect of Inclisiran and risks of adverse events were reviewed.Results There were totally 3 RCT included and the total sample size was 3660.Compared with placebo,Inclisiran significantly reduced the change rate of low-density lipoprotein-cholesterol(LDL-C,MD=-50.55,95%CI:-52.73～-48.38,P<0.0001),LDL-C variation(MD=-57.17,95%CI:-62.91～-51.43,P<0.0001)and major adverse cardiovascular events(MACE,RR=0.78,95%CI:0.65～0.93,P=0.006),while the effect of Inclisiran on the total adverse events was similar to that of placebo(RR=1.01,95%CI:0.97～1.04,P=0.62).TSA results showed that the outcomes of MACE observed by current information quantity were conclusive,but outcomes of the total adverse events needed more researches and demonstrations.The results of Harbord regression analysis showed that both MACE and the total adverse events were not in publication bias.The results of GRADE education showed that the evidence quality of LDL-C change rate,MACE and the total adverse events were high,and LDL-C variation was low.Conclusion Inclisiran has a potential to reduce LDL-C level and cardiovascular risk,and its effect on the total adverse events is similar to that of placebo,which has the value of further study.