South Australian Health and Medical Research Institute, University of Adelaide, PO Box 11060, Adelaide, SA, 5001, Australia.
BioDrugs. 2017 Jun;31(3):167-174. doi: 10.1007/s40259-017-0220-y.
The clinical reality of residual risk despite statin (HMG-CoA reductase inhibitor) therapy and emergence of statin intolerance support the need to develop additional lipid-lowering strategies. Proprotein convertase subtilisin kexin type 9 (PCSK9) has received considerable attention by virtue of genetic and clinical studies that have revealed its pivotal role in the regulation of cholesterol homeostasis. Monoclonal antibodies have been developed targeting PCSK9, which have been demonstrated to produce profound low-density lipoprotein cholesterol (LDL-C) lowering when provided as monotherapy or in combination with statins. With the reports that the PCSK9 inhibitor evolocumab has a favorable impact on both plaque progression and cardiovascular outcomes, these findings begin to translate the benefits of PCSK9 inhibition from lipids to the vessel wall and ultimately to clinical outcomes. The clinical implications for the use of these agents are reviewed in this article.
尽管使用他汀类药物（HMG-CoA 还原酶抑制剂）治疗和出现他汀类药物不耐受，但仍存在临床残余风险，这支持需要开发额外的降脂策略。前蛋白转化酶枯草溶菌素 9（PCSK9）因其遗传和临床研究揭示了其在胆固醇稳态调节中的关键作用而受到广泛关注。已经开发出针对 PCSK9 的单克隆抗体，当作为单药或与他汀类药物联合使用时，这些单克隆抗体已被证明可显著降低低密度脂蛋白胆固醇（LDL-C）。随着报告称 PCSK9 抑制剂依洛尤单抗对斑块进展和心血管结局均有有利影响，这些发现开始将 PCSK9 抑制的益处从脂质转化为血管壁，最终转化为临床结局。本文综述了这些药物的临床应用意义。
