靶向低密度脂蛋白胆固醇的创新降脂药物研究进展  

Research advances of innovative lipid-lowering drugs targeting low-density lipoprotein cholesterol

作　　者：王琦 孙彬[1,2] 艾常虹 WANG Qi;SUN Bin;AI Changhong(Department of Clinical Medicine,Hulun Buir People’s Hospital,Inner Mongolia Hulun Buir 021000,China;Hulunbuir Medical School,Nationalities University of Inner Mongolia,Inner Mongolia Hulun Buir 021000,China;Department of Pharmacy,Hulun Buir Sino-Mongolia Hospital,Inner Mongolia Hulun Buir 021000,China)

机构地区：[1]呼伦贝尔市人民医院临床药学部,内蒙古呼伦贝尔021000 [2]内蒙古民族大学呼伦贝尔医学院,内蒙古呼伦贝尔021000 [3]呼伦贝尔市中蒙医院药剂科,内蒙古呼伦贝尔021000

出　　处：《中国医院药学杂志》2024年第21期2540-2547,共8页Chinese Journal of Hospital Pharmacy

基　　金：内蒙古医学科学院公立医院科研联合基金科技项目(编号:2023GLLH0365)。

摘　　要：低密度脂蛋白胆固醇(LDL-C)升高是动脉粥样硬化性心血管疾病(atherosclerotic cardiovascular disease,ASCVD)的重要危险因素之一,绝大多数国家或地区的血脂管理指南均推荐LDL-C作为降脂治疗的首要目标,同时以危险分层确定其目标值。大量循证证据表明,他汀类药物通过显著降低血清LDL-C水平,可有效降低ASCVD患者心血管事件发生率,但ASCVD高风险人群的LDL-C降脂达标率现状仍然堪忧,临床上仍存在较多未被满足的降脂治疗需求。为应对这一难题,研究人员探索并发现了几类具有潜在创新作用机制的LDL-C靶向药物,包括前蛋白转化酶枯草杆菌蛋白酶9抑制剂(单克隆抗体如依洛尤单抗、阿利西尤单抗和托莱西单抗,小干扰RNA分子如英克司兰),ATP-柠檬酸裂解酶抑制剂(贝派地酸)、血管生成素样蛋白-3抑制剂(依苏维单抗);此外,许多靶向LDL-C的新兴药物目前正在研究中。该文将综述上述药物的临床药理学及其心血管获益,同时总结靶向LDL-C的创新药物的循证管理进展。Elevated low-density lipoprotein cholesterol(LDL-C)is a significant risk factor for atherosclerotic cardiovascular disease(ASCVD).In recent lipid management guidelines,LDL-C has been recommended as a primary target for lipid-lowering therapy in most countries or regions.And target levels are based upon risk stratification.Extensive evidence indicates that statins could effectively decrease the incidence of cardiovascular events in ASCVD patients through a marked reduction of serum LDL-C level.However,the current rate of LDL-C target attaining in high-risk ASCVD populations remains low,indicating numerous unmet needs in lipid-lowering therapy.To address this challenge,researchers have identified several LDL-C-targeting drugs with potentially innovative mechanisms of action.These include proprotein convertase subtilisin/kexin type 9(PCSK9)inhibitors(e.g.monoclonal antibodies of evolocumab,alirocumab and torcetrapib,as well as small interfering RNA molecule of inclisiran),ATP-citrate lyase inhibitor(e.g.bempedoic acid)and angiopoietin-like protein 3 inhibitor(e.g.evinacumab).Additionally many emerging LDL-C-targeting drugs are currently under evaluations.Focusing upon clinical pharmacology and cardiovascular benefits of these drugs,this review summarized the evidence-based management protocols of innovative LDL-C-targeting therapies.

关 键 词：血脂异常 低密度脂蛋白 依洛尤单抗 阿利西尤单抗 英克司兰 贝派地酸 依苏维单抗 

分 类 号：R965.1[医药卫生—药理学]