【摘要】 目的系统评价Evolocumab治疗血脂异常的有效性与安全性。方法计算机检索Pubmed、Embase、The Cochrane Library、Clinical Trials.gov、中国生物医学文献数据库和中国学术期刊全文数据库,筛选并纳入Evolocumab调节血脂异常的随机对照试验(RCT),检索时限为建库至2015年9月,由两名评价者根据纳入、排除标准独立筛选文献、提取资料和评价纳入研究的方法学质量。采用Rev Man5.2软件对符合质量标准的RCT进行合并分析。结果最终纳入11个RCT,共计9500例患者。有效性分析结果显示:与安慰剂相比,Evolocumab 420 mg每4周1次(Q4W)皮下注射可降低低密度脂蛋白胆固醇(LDL-C)56.38%(95%CI:61.54~51.22,P<0.05);Evolocumab 140 mg Q2W可降低LDL-C 60.54%(95%CI:68.15~52.94,P<0.05),并显著降低总胆固醇(TC)、非高密度脂蛋白胆固醇(NonHDL-C)、极低密度脂蛋白胆固醇(VLDL-C)、三酰甘油(TG)、脂蛋白a(Lp(a)和载脂蛋白B(Apo B),同时升高高密度脂蛋白胆固醇(HDL-C)和载脂蛋白A1(Apo A1)。安全性分析结果显示,在严重治疗相关不良反应(SAEs)和药物不良反应导致停药方面,Evolocumab组与安慰剂组之间差异无统计学意义(P>0.05)。最常见的不良反应为鼻咽炎、上呼吸道感染、背痛、注射部位反应、头痛、肌痛和腹泻,结果显示Evolocumab组与安慰剂组之间差异无统计学意义(P>0.05),丙氨酸转氨酶(ALT)或天冬氨酸转氨酶(AST)升高大于3倍正常值上限(ULN),两组间差异无统计学意义(P>0.05),而治疗相关不良事件(TEAEs)、肌酸激酶(CK)升高大于5倍ULN,两组间差异有统计学意义(P<0.05)。结论本研究结果表明,与安慰剂组相比,Evolocumab可显著改善各项血脂指标,而常见不良反应两组间无明显差异。但上述结论仍需开展大样本高质量、随访时间更长的RCT进一步论证。更多还原

【Abstract】 Objective To systemically evaluate the efficacy and safety of Evolocumab with in treatment of dyslipidemia. Methods The computer search including Pub Med, EMbase, the Cochrane Library, Clinical Trial.gov, CBM and CNKI were conducted to collect the randomized controlled trials(RCTs) for Evolocumab in treatment of dyslipidemia, the retrieval period was from the database establishment until September 2015. Two reviewers identified the literatures independently according to inclusion and exclusion criteria, extracted the information and evaluated the quality of assessment methods of each study, then Meta-analysis was performed by Rev Man 5.2 software. Results A total of 11 RCTs comprising 9500 subjects were enrolled. Compared with placebo, Evolocumab 420 mg once every 4 weeks(Q4W) subcutaneous injection significantly reduced LDL-C by 56.38%(95%CI:61.54~51.22, P<0.05), Evolocumab 140 mg Q2 W reduced low-density lipoprotein cholesterol(LDL-C) by 60.54%(95%CI:68.15~52.94, P<0.05). It also could significantly reduce total cholesterol(TC), non-high-density lipoprotein cholesterol(NonHDL-C), Very low density lipoprotein cholesterol(VLDL-C), triglyceride(TG), lipoprotein-a and Apolipoprotein B(Apo B). And it also increased high-density lipoprotein cholesterol(HDL-C) and apolipoprotein A1(Apo A1) significantly. In safety analysis, there were no difference between Evolocumab and placebo in SAEs and leading to discontinuation(P>0.05). The most common adverse events are nasopharyngitis, upper respiratory tract infection, back pain, injection-site reaction, headache, myalgia and diarrhea, the analysis results showed that there was no significant difference between the two groups(P>0.05). For Alanine transaminase(ALT) or aspartate aminotransferase(AST)>3 upper limit of normal(ULN), there was no significant difference between the two groups(P>0.05), but on Treatment-emergent adverse events(TEAE), creatine kinase(CK)>5ULN, there was significant difference between the two groups(P<0.05). Conclusion Evolocumab resulted in a significant improvement in lipid parameters, but showed no significant difference in common adverse events while comparing with placebo. More high quality randomized controlled trials with large sample sizes are need to further validate this result in the future.更多还原