[1]李莎 王秀秀 熊峰.小核酸药物Inclisiran降低低密度脂蛋白胆固醇治疗研究进展[J].心血管病学进展,2023,(7):613.[doi:10.16806/j.cnki.issn.1004-3934.2023.07.009]
 LI Sha,WANG Xiuxiu,XIONG Feng.Treatment of Low Density Lipoprotein Cholesterol with Small Nucleic Acid Drug Incisiran[J].Advances in Cardiovascular Diseases,2023,(7):613.[doi:10.16806/j.cnki.issn.1004-3934.2023.07.009]
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小核酸药物Inclisiran降低低密度脂蛋白胆固醇治疗研究进展()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2023年7期
页码:
613
栏目:
综述
出版日期:
2023-07-25

文章信息/Info

Title:
Treatment of Low Density Lipoprotein Cholesterol with Small Nucleic Acid Drug Incisiran
作者:
李莎 王秀秀 熊峰
(西南交通大学医学院 西南交通大学附属医院 成都市第三人民医院,四川 成都 610031)
Author(s):
LI Sha WANG XiuxiuXIONG Feng
(Southwest Jiaotong University College of Medicine,The Affiliated Hospital of Southwest Jiaotong University,The Third Peoples Hospital of Chengdu,Chengdu 610031,Sichuan,China )
关键词:
心血管疾病小核酸药物Inclisiran血脂紊乱ORION
Keywords:
Cardiovascular disease Small nucleic acid drugs InclisiranDyslipidemia ORION
DOI:
10.16806/j.cnki.issn.1004-3934.2023.07.009
摘要:
心血管疾病是全球死亡的主要原因。血脂异常是心血管疾病最常见危险因素之一,而他汀类药物治疗已显示出一定局限性。Inclisiran,一种小干扰RNA分子,通过抑制低密度脂蛋白胆固醇代谢中前蛋白转化酶枯草杆菌蛋白酶9的合成,增加肝细胞膜上低密度脂蛋白受体的数量,已成为治疗高胆固醇血症的新药物。现就首个上市的作为预防心血管疾病的小核酸降脂药物inclisiran的作用机制,在低密度脂蛋白胆固醇治疗中有效性及安全性研究进展作一综述。
Abstract:
Cardiovascular disease is the main cause of death worldwide. Dyslipidemia is one of the most common risk factors of cardiovascular disease, and statin therapy has shown some limitations. Inclisiran,a small interfering RNA molecule, increases the amount of low-density lipoprotein receptor on the liver membrane by inhibiting the synthesis of preprotein converting enzyme subtilisin kexin 9 in LDL-C metabolism, becoming a new drug for the treatment of hypercholesterolemia. We review the mechanism,efficacy and safety of inclisiran, the first small nucleic acid lipid-lowering drug to be marketed for the prevention of cardiovascular disease,as well as in the treatment of hypercholesterolemia in this article

参考文献/References:

[1]. 《中国心血管健康与疾病报告2021》概述[J].中国心血管病研究,2022,20(07):577-596.
[2]. Waters DD. What the statin trials have taught us[J]. Am J Cardiol,2006,98(1):129-134.
[3]. Gitt AK,Lautsch D,Ferrieres J,et al. Low-density lipoprotein cholesterol in a global cohort 57,885 statin-treated patients[J]. Atherosclerosis,2016,255:200-209.
[4]. Dyrbu? K,Osadnik T,Desperak P,et al. Evaluation of dyslipidaemia and the impact of hypolipidemic therapy on prognosis in high and very high risk patients through the Hyperlipidaemia Therapy in tERtiary Cardiological cEnTer (TERCET) Registry[J]. Pharmacol Res,2018,132:204-210.
[5]. Bergeron N,Phan BA,Ding Y,et al. Proprotein convertase subtilisin/kexin type 9 inhibition:a new therapeutic mechanism for reducing cardiovascular disease risk[J]. Circulation,2015,132(17):1648-1666.
[6]. Dragan S,Serban MC,Banach M. Proprotein convertase subtilisin/kexin 9 inhibitors:an emerging lipid-lowering therapy?[J]. J Cardiovasc Pharmacol Ther ,2015,20(2):157-168.
[7]. Seidah NG,Benjannet S,Wickham L,et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1):liver regeneration and neuronal differentiation[J]. Proc Natl Acad Sci U S A,2003,100(3):928-933.
[8]. Barale C,Melchionda E,Morotti A,et al. PCSK9 biology and its role in atherothrombosis[J]. Int J Mol Sci,2021,22(11):5880.
[9]. Kosmas CE,Mu?oz Estrella A,Sourlas A,et al. Inclisiran:a new promising agent in the management of hypercholesterolemia[J]. Diseases,2018,6(3):63.
[10]. Kosmas CE,Mu?oz Estrella A,Skavdis A,et al. Inclisiran for the treatment of cardiovascular disease: a short review on the emerging data and therapeutic potential [J]. Ther Clin Risk Manag,2020,16:1031-1037.
[11]. Malo J, Parajuli A, Walker SW. PCSK9:from molecular biology to clinical applications[J]. Ann Clin Biochem,2020,57(1):7-25.
[12]. Kuzmich N,Andresyuk E,Porozov Y,et al. PCSK9 as a target for development of a new generation of hypolipidemic drugs[J]. Molecules,2022,27(2):434.
[13]. Fitzgerald K,Frank-Kamenetsky M,Shulga-Morskaya S,et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers:a randomised,single-blind,placebo-controlled,phase 1 trial. Lancet,2014,383(9911):60-68.
[14]. Fitzgerald K,White S,Borodovsky A,et al. A highly durable RNAi therapeutic inhibitor of PCSK9[J]. N Engl J Med,2017,376(1):41-51.
[15]. Lagace TA,Curtis DE,Garuti R,et al. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice[J]. J Clin Invest,2006,116(11):2995-3005.
[16]. Kosmas CE,DeJesus E,Morcelo R,et al. Lipid-lowering interventions targeting proprotein convertase subtilisin/kexin type 9 (PCSK9):an emerging chapter in lipid-lowering therapy[J]. Drugs Context,2017,6:212511.
[17]. Ray KK,Stoekenbroek RM,Kallend D,et al. Effect of an siRNA therapeutic targeting PCSK9 on atherogenic lipoproteins:prespecified secondary end points in ORION 1[J]. Circulation,2018,138(13):1304-1316.
[18]. Ray KK,Landmesser U,Leiter LA,et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol[J]. N Engl J Med,2017,376(15):1430-1440.
[19]. Henney NC,Banach M,Penson PE. RNA silencing in?themanagement ofdyslipidemias[J]. Curr Atheroscler Rep,2021,23(11):69.
[20]. Hovingh GK,Lepor NE,Kallend D,et al. Inclisiran durably lowers low-density lipoprotein cholesterol and proprotein convertase subtilisin/kexin type 9 expression in homozygous familial hypercholesterolemia:the ORION-2 pilot study[J]. Circulation,2020,141(22):1829-1831.
[21]. Kosmas CE,Mu?oz Estrella A,Sourlas A,et al. Inclisiran in dyslipidemia[J]. Drugs Today (Barc), 2021,57(5):311-319.
[22]. Kallend D,Stoekenbroek R,He Y,et al. Pharmacokinetics and pharmacodynamics of inclisiran,a small interfering RNA therapy,in patients with hepatic impairment[J]. J Clin Lipidol,2022,16(2):208-219.
[23]. Kallend D,Mason J,Smith PF,et al. An evaluation of a supratherapeutic dose of inclisiran on cardiac repolarization in healthy volunteers:A phase I,randomized study[J]. Clin Transl Sci,2022,15(11):2663-2672.
[24]. Toth PP,Bray S,Villa G,et al. Network meta-analysis of randomized trials evaluating the comparative efficacy of lipid-lowering therapies added to maximally tolerated statins for the reduction of low-density lipoprotein cholesterol[J]. J Am Heart Assoc,2022,11(18):e025551.
[25]. Hardy J,Niman S,Pereira E,et al. A critical review of the efficacy and safety of inclisiran. Am J Cardiovasc Drugs,2021,21(6):629-642.
[26]. Landmesser U,Haghikia A,Leiter LA,et al. Effect of inclisiran,the small-interfering RNA against proprotein convertase subtilisin/kexin type 9,on platelets,immune cells,and immunological biomarkers:a pre-specified analysis from ORION-1[J]. Cardiovasc Res,2021,117(1):284-291.
[27]. Galactionova K,Salari P,Mattli R,et al. Cost-effectiveness,burden of disease and budget impact of inclisiran:dynamic cohort modelling of a real-world population with cardiovascular disease[J]. Pharmacoeconomics,2022,40(8):791-806.
[28]. Desai NR,Campbell C,Electricwala B,et al. Cost effectiveness of inclisiran in atherosclerotic cardiovascular patients with elevated lowdensity lipoprotein cholesterol despite statin use:a threshold analysis[J]. Am J Cardiovasc Drugs,2022,22(5):545-556.

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更新日期/Last Update: 2023-08-18