Inclisiran治疗高胆固醇血症的荟萃分析和试验序贯分析

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

目的Inclisiran是一种抑制前蛋白转化酶枯草溶菌素9(PCSK9)合成的小干扰RNA,具有显著降低低密度脂蛋白胆固醇(LDL-C)水平的潜力,这项研究评估了Inclisiran在高胆固醇血症和心血管预后中的效果及安全性。方法检索中国生物医学文献、中国知网、万方、维普、PubMed、EMbase、the Cochrane Library、Web of Science数据库,时间均从建库至2021月3月,对公开发表的Inclisiran治疗高胆固醇血症的随机对照试验进行荟萃分析和试验序贯分析(TSA),评价Inclisiran的调脂效果和不良事件风险。结果共纳入了3个RCT,总样本量3660例。与安慰剂相比,Inclisiran能显著降低LDL-C变化率(MD=-50.55,95%CI:-52.73~-48.38,P<0.0001),LDL-C变化量(MD=-57.17,95%CI:-62.91~-51.43,P<0.0001)和主要心血管不良事件(MACE,RR=0.78,95%CI:0.65~0.93,P=0.006),而总不良事件相当(RR=1.01,95%CI:0.97~1.04,P=0.62)。TSA示当前信息量观察到的MACE结局具有结论性,但总不良事件结局有待更多研究论证。Harbord回归示MACE和总不良事件均不存在发表偏倚。GRADE评价示LDL-C变化率、MACE、总不良事件的证据质量为高,LDL-C变化量的证据质量为低。结论Inclisiran具有降低LDL-C水平和心血管风险的潜力,总不良事件可能和安慰剂相当,具有进一步研究探索的价值。

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.