PCSK9抑制药Alirocumab治疗血脂异常有效性的Meta分析

Meta Analysis of Efficacy of an Anti-PCSK9 Antibody Alirocumab for Treating Dyslipidemia

目的:评价前蛋白转化酶枯草杆菌蛋白酶/溶菌素9(PCSK9)抑制药Alirocumab治疗血脂异常的有效性。方法:搜索数据库Pub Med、Embase、the Cochrane Library、Clinical Trials.gov、中国知网、万方数据库和国内外相关心血管会议记录,收集Alirocumab对比安慰剂和依折麦布治疗血脂异常有效性评价的2期、3期临床随机对照试验,采用RevMan 5.3软件对收集数据进行Meta分析。结果:纳入的18篇研究中包含6 748例研究对象,其中,13个研究比较了Alirocumab和依折麦布的效果,研究对象例数分别为3 606例和1 658例;5个研究比较了Alirocumab和安慰剂的效果,研究对象例数分别为864例和620例。Meta分析结果显示:与依折麦布和安慰剂相比,Alirocumab显著降低低密度脂蛋白(LDL-C)水平[依折麦布:MD=-30.51%,95%CI(-33.68%,-27.33%);安慰剂:MD=-52.25%,95%CI(-55.85%,-48.65%)]。对于已服用稳定剂量他汀类药物的患者,Alirocumab可进一步降低LDL-C水平[依折麦布:MD=-30.30%,95%CI(-34.43%,-26.17%);安慰剂:MD=-50.64%,95%CI(-54.95%,-46.33%)]。Alirocumab对其他脂质也产生有利影响:降低非高密度脂蛋白(non-HDL-C)、载脂蛋白B(Apo B)、三酰甘油(TC)和胆固醇(TG)的水平,升高高密度脂蛋白(HDL-C)和载脂蛋白A-1(Apo A-1)的水平。结论:PCSK9抑制药Alirocumab为已强化他汀治疗后LDL-C水平仍不能达标以及他汀类单药不耐受的高胆固醇血症或高危心血管疾病风险的患者提供了新的治疗选择方案。

Objective： The purpose of this Meta-analysis was to evaluate the efficacy of Alirocumab （ an anti-PC- SK9 antibody） for treating dyslipidemia. Methods： Pubmed, Embase, the Coehrane Library, Clinical Trials. gov databases, CNKI, VIP database and recent conferences were searched for phase 2 and 3 randomized controlled trials （RCTs） comparing Afirocumab with placebo or ezetimibe for dyslipidemia. Meta analysis of the data were extracted and analyzed using the Software RevMan 5.3. Results：Included 18 RCTs with a total of 6 748 patients, 13 RCTs were compared A.lirocumab （ n -- 3606 ） with ezetimibe （ n = 1658 ） and 5 RCTs were compared Alirocumab （ n = 864 ） with placebo （ n = 620）. LDL-C in Aliroeumab group was significantly decreased than those in ezetimibe group [ MD = -30.50%, 95% CI： （ -33.68%, -27.33% ） ], and than those in placebo group [MD = -52.25%, 95% CI： （ -55.85%, -48.65% ） ]. LDL-C in Ali- rocumab group was significantly decreased than those in ezetimibe group [ MD = - 30.30%, 95% CI： （ - 34.43% , - 26.17% ） ], and than those in placebo group [ MD = - 50.64% , 95% CI： （ - 54.95% to - 46.33% ） ] though patients were on stable statin treatment. And also significant and favorable changes were also detected in other lipids of Alirocumab group. Aliroeumab substantially reduced the level of Apo B, Non-HDL-C, Lp （a）, TGs and TC, increased the HDL-C and Apo A-1 level. Conclusion： The PCSK9 inhibitor Alirocumab could be an add-on therapy to lipid-lowering drugs for patients who had established dyslipidemia or high cardiovascular （CV） risk with LDL-C inadequately controlled on stable statin treatment or statinintolerance.