Wu Na-Qiong, Li Sha, Li Jian-Jun
Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, 167 BeiLiShi Road, Beijing, 100037, China.
Cardiovasc Drugs Ther. 2015 Apr;29(2):159-69. doi: 10.1007/s10557-015-6582-9.
Hyperlipidemia is a predominant risk factor for cardiovascular disease (CVD). Statins have been successfully used to treat patients with dyslipidemia and decrease the events of CVD in addition to application of various other non-statin-lowering cholesterol agents, such as ezetimibe and niacin. However, there are still residual risks in patients with atherosclerotic CVD. Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9), which was first identified in 2003, has been suggested to play an important role in the metabolism of low-density lipoprotein cholesterol (LDL-C). PCSK9 degrades the LDL-receptor, which may be pharmacologically targeted to improve the lipoprotein profile and future cardiovascular outcomes in patients with dyslipidemia. Several approaches to inhibiting PCSK9 activity have been theoretically proposed. Among them, monoclonal antibodies have been considered as the most promising strategy because of their large effect on lowering lipids as monotherapy and in combination with statins or ezetimibe. In this review, we mainly focus on the current status of monoclonal antibodies of PCSK9 and clinical trial results for an update on clinical application of monoclonal antibodies of PCSK9. The particular effects of monoclonal antibodies of PCSK9 on lipid profiles are also discussed.
高脂血症是心血管疾病（CVD）的主要危险因素。除了应用各种其他非他汀类降胆固醇药物（如依折麦布和烟酸）外，他汀类药物已成功用于治疗血脂异常患者并降低CVD事件。然而，动脉粥样硬化性CVD患者仍存在残余风险。最近，2003年首次发现的前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）被认为在低密度脂蛋白胆固醇（LDL-C）的代谢中起重要作用。PCSK9会降解LDL受体，从药理学角度来看，针对该受体可能会改善血脂异常患者的脂蛋白谱和未来心血管结局。理论上已经提出了几种抑制PCSK9活性的方法。其中，单克隆抗体因其作为单一疗法以及与他汀类药物或依折麦布联合使用时对降低血脂有显著效果，而被认为是最有前景的策略。在这篇综述中，我们主要关注PCSK9单克隆抗体的现状以及临床试验结果，以更新PCSK9单克隆抗体的临床应用情况。还讨论了PCSK9单克隆抗体对血脂谱的具体影响。
