Durairaj Ashwin, Sabates Alberto, Nieves Jonathan, Moraes Brian, Baum Seth
Internal Medicine Resident, Florida Atlantic University (FAU), 11397 Water Oak Place, Davie, FL, 33330, USA.
Internal Medicine Resident, FAU, Boca Raton, FL, 33431, USA.
Curr Treat Options Cardiovasc Med. 2017 Aug;19(8):58. doi: 10.1007/s11936-017-0556-0.
Atherosclerotic cardiovascular disease (ASCVD) remains the number one killer in the western world. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and ezetimibe has been shown to reduce the risk of cardiovascular events. Now, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mabs) are available for high-risk individuals with ASCVD or familial hypercholesterolemia on maximally tolerated statin therapy but requiring greater LDL-C reduction. PCSK9 mab outcome trial results from the Further Cardiovascular Outcomes Research with PCSK9 Inhibitions in Subjects with Elevated Risk (FOURIER) study, which was presented at the American College of Cardiology in March 2017, which demonstrated a decrease of 15% in primary and 20% secondary end points over a 2-year period [1••]. These results firmly demonstrated additional benefit beyond maximally tolerated statin therapy in high-risk individuals. Thus, management of LDL-C will soon become more complex, as a new class of medication is added to our standard armamentarium. This review explores the discovery of PCSK9, its biology and physiology, and the development of the PCSK9 mabs.
动脉粥样硬化性心血管疾病（ASCVD）仍是西方世界的头号杀手。他汀类药物和依折麦布降低低密度脂蛋白胆固醇（LDL-C）已被证明可降低心血管事件风险。现在，对于接受最大耐受剂量他汀类药物治疗但仍需要更大程度降低LDL-C的ASCVD高危个体或家族性高胆固醇血症患者，前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）单克隆抗体（mabs）可供使用。2017年3月在美国心脏病学会上公布的“PCSK9抑制剂在高危受试者中的进一步心血管结局研究（FOURIER）”的PCSK9 mab结局试验结果显示，在2年期间主要终点降低了15%，次要终点降低了20%[1••]。这些结果有力地证明了在高危个体中，除最大耐受剂量他汀类药物治疗外还有额外益处。因此，随着一类新药物加入我们的标准治疗手段，LDL-C的管理将很快变得更加复杂。本综述探讨了PCSK9的发现、其生物学和生理学以及PCSK9 mab的研发情况。
