PCSK9抑制剂在高胆固醇血症中的定位

Sunil Chaudhry, Abhijit Trailokya
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摘要

pcsk9抑制剂目前的市场规模为30亿美元,到未来10年,发达国家的市场规模将增至130亿美元。血脂异常和其他脂质疾病患病率的上升与不平衡的生活方式和不断增加的酒精和烟草使用导致的脂质代谢有关。PCSK9抑制剂是一种可注射的单克隆抗体,可灭活PCSK9受体。PCSK9抑制降低LDL受体的降解,从而增加肝细胞上具有功能的LDL受体的数量,降低血液中可致动脉粥样硬化的LDL颗粒的数量。对于心血管风险极高的患者,在他汀类药物中加入PCSK9抑制剂和依zetimibe,可显著降低心肌梗死(MI)和中风的绝对风险。已知他汀类药物可上调PCSK9编码基因。PCSK9抑制剂每两个月或一个月给药,相当安全。家族性高胆固醇血症(FH)是一种常见的遗传性脂质代谢疾病,在LDLR、APOB或PCSK9这三个基因中有一个发生突变。这些患者发生冠状动脉事件的风险是一般人群的22倍。在低剂量他汀类药物治疗中加入PCSK9抑制剂将更有效地降低LDL并避免他汀类药物的副作用。PCSK9抑制剂可以促进动脉粥样硬化斑块的稳定和消退,从而避免或延迟主要的不良心脏事件。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Positioning of PCSK9 Inhibitors in hypercholesterolemia
PCSK 9 inhibitors currently have a market of 3 billion USD and by next 10 years it will raise to 13 billion USD in developed world. The rising prevalence of dyslipidemia and other lipid disorders are linked to lipid metabolism due to an unbalanced lifestyle and rising alcohol and tobacco use. PCSK9 inhibitors are injectable monoclonal antibodies that inactivate PCSK9 receptors. PCSK9 inhibition decreases degradation of the LDL receptor, thus raising the number of functioning LDL receptors on hepatocytes and lowering the number of LDL particles in the blood, which are atherogenic. For patients with very high cardiovascular risk, PCSK9 inhibitors and ezetimibe are added to statins, where they significantly lower absolute risk for myocardial infarction (MI) and stroke. Statins are known to upregulate PCSK9 encoding gene. PCSK9 inhibitors are given bimonthly or monthly and are reasonably safe. Familial Hypercholesterolemia (FH) a common inherited disorder of lipid metabolism, has mutations in one of these 3 genes: LDLR, APOB or PCSK9. These patients have 22 times more risk of coronary event than general population. Addition of a PCSK9 inhibitor to low dose statin therapy will be more effective in lowering LDL and avoiding the side effects of statins. PCSK9 inhibitors can contribute to both the stabilization and regression of atherosclerotic plaques and thereby avoid or delay major adverse cardiac events.
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