载脂蛋白B合成抑制剂治疗血脂异常的有效性与安全性的Meta分析

Efficacy and safety of mipomersen in treatment of dyslipidemia: A meta-analysis of randomized controlled trails

目的:应用Meta分析系统评价载脂蛋白B(apo B)合成抑制剂(mipomersen)治疗血脂异常的有效性与安全性。方法:计算机检索Pubmed、Embase、Cochrane library截止至2016年10月31日,电子期刊,纳入mipomersen与安慰剂比较的随机对照试验。按照Cochrane Handbook提供的方法对纳入文献进行质量评估并提取有效数据,应用Rev Man5.3软件进行Meta分析。结果:最终纳入9篇文献共505例患者。Meta分析结果显示:与安慰剂对比,mipomersen能显著降低LDL-C水平的百分比(-31.69%,95%CI:-38.30^-25.08,P<0.00001);降低apo B水平的百分比(-32.72%,95%CI:-38.05^-27.39,P<0.00001),并能降低N-HDL-C、TC、TG、LP(a)等血脂水平。在安全性方面,与对照组相比,mipomersen增加了患者注射部位反应的风险(OR=8.88,95%CI:4.09~19.28,P<0.00001);流感综合征的风险(OR=2.08(95%CI:1.28~3.37,P=0.003));肝酶学升高的风险(ALT≥3ULN OR=9.92,95%CI:2.97~33.10,P=0.0002)及脂肪肝的风险(OR=13.56,95%CI:3.02~60.82,P<0.0007)。结论:mipomersen能有效降低血脂异常患者的LDL-C、apo B、N-HDL-C、TG、TC、LP(a)的水平,但有明显的不良反应,纳入文献中并未观察到主要心血管事件的发生。

Objective： The purpose of this meta-analysis was to evaluate the efficacy and safety of mipomersen in treatment of dyslipidemia. Methods： The databases of Pubmed,Embase,Cochrane Library of electronic journal were retrieved with computer for searching randomized controlled trials comparing mipomersen with placebo for dyslipidemia by end of 2016-10-31. The quality of the included literatures were assessed according to the method provided by Coehrane Handbook. Data were extracted and analyzed using the Software RevMan5.3. Results： A total of 9 documents with 505 patients were finally enrolled, recta-analysis shows： comparing with placebo, mipomersen decreased the percent of LDL-C levels significantly （ -31.69% ,95 % CI： - 38.30 - - 25.08, P 〈 0. 00001 ） ; decreased the percent of apoB levels [ - 32. 72% , 95% CI： - 38.05 - - 27. 39, P 〈 0. 00001 ） , at the same time, reduced the percent of levels of Non-HDL-C, TG, TC, LP（a） and so on. In the aspect of safety, mipomersen compared with placebo increased the risks of injection-site reaction（ OR = 8.88, （95% CI,4. 09 - 19. 28, P 〈 0. 00001 ）, fliu-like symptoms （ OR = 2. 08,95% CI： 1.28 - 3.37, P = 0. 003） , alanine aminotransferase ≥ 3X upper limit of normal （ OR = 9.92,95% CI： 2. 97 - 33.10, P = 0. 0002） ,hepatic steatosis （ OR = 13.56,95% CI：3.02 - 60. 82, P 〈 0. 0007 ）. Conclusion ： mipomersen can effectively reduce the levels of LDL-C, apoB, no-HDL-C, TC, TG, LP （ a ） in dyslipidemia patients. , although have many adverse events, not observed the incidence of major adverse cardiovascular events.