Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University and School of Medicine, Baltimore, MD
CGH Medical Center, Sterling, IL.
J Am Heart Assoc. 2017 Oct 2;6(10):e005367. doi: 10.1161/JAHA.116.005367.
The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low-density lipoprotein cholesterol (LDL-C) when added to statin therapy in patients who need additional LDL-C reduction.
We conducted a systematic review and network meta-analysis of randomized trials of lipid-lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid-lowering therapies that enrolled patients requiring further LDL-C reduction while on maximally tolerated medium- or high-intensity statin, of which 15 could be relevant for inclusion in LDL-C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL-C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (-74.1%; 95% credible interval -79.81% to -68.58%), alirocumab 75 mg (-20.03%; 95% credible interval -27.32% to -12.96%), and alirocumab 150 mg (-13.63%; 95% credible interval -22.43% to -5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe.
PCSK9 inhibitors added to medium- to high-intensity statin therapy significantly reduce LDL-C in patients requiring further LDL-C reduction. The network meta-analysis showed a significant treatment difference in LDL-C reduction for evolocumab versus alirocumab.
在需要进一步降低 LDL-C 的患者中，在他汀类药物治疗的基础上添加前蛋白转化酶枯草溶菌素 9（PCSK9）抑制剂依洛尤单抗和阿利西尤单抗可显著降低 LDL-C。
我们对降脂治疗的随机试验进行了系统评价和网络荟萃分析，检索时间从数据库建立开始至 2016 年 8 月（共检索到 45058 条记录）。我们发现了 69 项降脂治疗试验，这些试验纳入了在最大耐受剂量的中或高强度他汀类药物治疗下仍需要进一步降低 LDL-C 的患者，其中 15 项试验可与依洛尤单抗、阿利西尤单抗、依折麦布和安慰剂作为治疗组纳入 LDL-C 降低网络。与安慰剂相比，PCSK9 抑制剂可使 LDL-C 降低 54%至 74%，与依折麦布相比降低 26%至 46%。在第 10 和 12 周的平均值时，每 2 周给予 140mg 依洛尤单抗与安慰剂相比，差异有统计学意义（-74.1%；95%可信区间-79.81%至-68.58%），与安慰剂相比，75mg 阿利西尤单抗（-20.03%；95%可信区间-27.32%至-12.96%）和 150mg 阿利西尤单抗（-13.63%；95%可信区间-22.43%至-5.33%）差异有统计学意义，持续时间至少为 12 周。PCSK9 抑制剂每月给药的治疗差异在方向和程度上相似。PCSK9 抑制剂与对照相比，不良事件相似。PCSK9 抑制剂与安慰剂或依折麦布相比，不良事件发生率相似。
在需要进一步降低 LDL-C 的患者中，在中至高剂量他汀类药物治疗的基础上添加 PCSK9 抑制剂可显著降低 LDL-C。网络荟萃分析显示，依洛尤单抗与阿利西尤单抗相比，在 LDL-C 降低方面存在显著的治疗差异。
