PCSK9抑制剂在动脉粥样硬化性心血管疾病中的临床研究进展

动脉粥样硬化性心血管疾病(ASCVD)现已成为危害人类健康的主要疾病之一。降低胆固醇治疗尤其是低密度脂蛋白-胆固醇(LDL-C),是ASCVD防治的基石,目前指南推荐控制LDL-C水平首选他汀类药物。但在临床实践中,经过他汀治疗的ASCVD患者仍存在较高剩留风险,另仍有部分患者不能耐受他汀类药物或在他汀类药物最大耐受剂量的情况下血脂仍不能达标。人前蛋白转化酶枯草溶菌素9(PCSK9)与LDL-C代谢密切相关,近年来大量基础和临床研究均证实PCSK9抑制剂能够显著降低血LDL-C水平,且耐受性和安全性良好。目前国外已批准PCSK9抑制剂用于临床。本文将系统综述有关PCSK9基因与血脂代谢的关系、PCSK9抑制剂的研发过程,总结其在基础和临床研究的最新进展。

Research progress of clinical trials related to PCSK9 inhibitors in atherosclerotic cardiovascular disease

Atherosclerotic cardiovascular disease (ASCVD) has become one of major diseases threatening human health.The cholesterol-lowering therapy is the cornerstone in the treatment and prevention of ASCVD.The guidelines have recommended that statins serve as the first choice to control low density lipoprotein-cholesterol (LDL-C)level.However,patients with ASCVD still have high residual risks after statins treatment.Moreover,some patients cannot be tolerable to statins,or even large doses of stains fail to successfully achieve the optimal level of LDL-C.Recently,a pro-protein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to be closely involved in LDLC metabolism.A large number of basic and clinical researches have proved that PCSK9 inhibitors can significantly reduce LDL-C level with good tolerance and safety.Meanwhile,PCSK9 inhibitors have been approved to be used clinically by the FDA.We systematically summarized the relationship between PCKS9 and lipid metabolism,further analyze the development process of PCSK9 inhibitor,and elaborate its basic and clinical research progresses.