[1]许海南 龙明智.新型降脂药物干扰小RNA Inclisiran最新研究进展[J].心血管病学进展,2021,(7):590-592，618.[doi:10.16806/j.cnki.issn.1004-3934.2021.07.004]
　XU Hainan,LONG Mingzhi.Small Interfering RNA Inclisiran[J].Advances in Cardiovascular Diseases,2021,(7):590-592，618.[doi:10.16806/j.cnki.issn.1004-3934.2021.07.004]
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新型降脂药物干扰小RNA Inclisiran最新研究进展()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2021年7期
页码:
590-592，618
栏目:
出版日期:
2021-07-25

文章信息/Info

Title:
Small Interfering RNA Inclisiran
作者:
许海南 龙明智
(南京医科大学第二附属医院心血管内科,江苏 南京 210011)
Author(s):
XU Hainan;  LONG Mingzhi
(Department of Cardiology,The Second Affiliated Hospital of Nanjing Medical University,Nanjing 210011,Jiangsu,China)
关键词:
低密度脂蛋白胆固醇; 前蛋白转化酶枯草溶菌素9; 干扰小RNA; Inclisiran
Keywords:
Low-density lipoprotein cholesterol; PCSK9; Small interfering RNA; Inclisiran
DOI:
10.16806/j.cnki.issn.1004-3934.2021.07.004
摘要:
血脂异常是动脉粥样硬化性疾病的主要危险因素之一，临床上有相当比例患者即使应用大剂量他汀类药物仍不能使低密度脂蛋白胆固醇（LDL-C）达标。前蛋白转化酶枯草溶菌素9（PCSK9）是近年来发现的非他汀类降脂药物作用的新靶点，目前已上市的针对PCSK9的单克隆抗体可使LDL-C水平显著降低，但因其需每2～4周的皮下注射及价格昂贵,使得患者的依从性降低，影响药物的推广应用。小分子干扰RNA inclisiran是一种经化学修饰的双链RNA，可直接抑制肝脏中PCSK9的合成，目前已公布的inclisiran大型临床试验ORION系列研究均表明其一年两次的给药方案可使LDL-C水平显著降低，现就inclisiran的最新研究进展加以综述。
Abstract:
Dyslipidemia is one of the main risk factors of atherosclerotic diseases. In clinic, a considerable proportion of patients can not reach the standard of low-density lipoprotein cholesterol (LDL-C) even with high-dose statins . Proprotein convertase subtilisin/kexin type 9(PCSK9) is a new target of nonstatin lipid-lowering drugs discovered in recent years. Currently, the monoclonal antibody against PCSK9 on the market can significantly reduce the LDL-C level. However, due to its subcutaneous injection every 2～4 weeks and high price, the compliance of patients is reduced, which affects the promotion and application of drugs. Small interfering RNA(inclisiran) is a kind of chemically modified double stranded RNA,which can directly inhibit the synthesis of PCSK9 in liver. The Orion series of published large-scale clinical trials of inclisiran have shown that its twice-a-year administration can significantly reduce the level of LDL-C. This article reviews the latest research progress of inclisiran.

参考文献/References:

[1] Ference BA,Yoo W,Alesh I,et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease:a Mendelian randomization analysis[J]. J Am Coll Cardiol,2012,60(25):2631-2639.

[2] 李建军. 血低密度脂蛋白胆固醇存在下限阈值吗? ODYSSEY OUTCOMES研究结果带来的新思考[J]. 中国循环杂志,2018,33(10):940-942.

[3] Mach F,Baigent C,Catapano AL,et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias:lipid modification to reduce cardiovascular risk[J]. Eur Heart J,2020,41(1):111-188.

[4] German CA,Shapiro MD. Small interfering RNA therapeutic inclisiran:a new approach to targeting PCSK9[J]. BioDrugs,2020,34(1):1-9.

[5] Bamji AN. Do PCSK9 inhibitors do anything more than reduce LDL cholesterol[J]. BMJ,2020,368:m1159.

[6] Carthew RW,Sontheimer EJ. Origins and mechanisms of miRNAs and siRNAs[J]. Cell,2009,136(4):642-655.

[7] Levin AA. Treating disease at the RNA level with oligonucleotides[J]. N Engl J Med,2019,380(1):57-70.

[8] 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.

[9] Nair JK,Willoughby JL,Chan A,et al. Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing[J]. J Am Chem Soc,2014,136(49):16958-169561.

[10] Fernández-Ruiz I. Twice-yearly inclisiran injections halve LDL-cholesterol levels[J]. Nat Rev Cardiol,2020,17(6):321.

[11] 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.

[12] 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[J]. Lancet,2014,383(9911):60-68.

[13] Landmesser U,Haghikia A,Leiter LA,et al .Effect of inclisiran,the siRNA 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.

[14] Nishikido T,Ray KK. Inclisiran for the treatment of dyslipidemia[J]. Expert Opin Investig Drugs,2018,27(3):287-294.

[15] 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.

[16] Leiter LA,Teoh H,Kallend D,et al. Inclisiran lowers LDL-C and PCSK9 irrespective of diabetes status:the ORION-1 randomized clinical trial[J]. Diabetes Care,2019,42(1):173-176.

[17] Ray KK,Wright RS,Kallend D,et al. Two phase 3 trials of inclisiran in patients with elevated LDL cholesterol[J]. N Engl J Med,2020,382(16):1507-1519.

[18] Raal FJ,Kallend D,Ray KK,et al. Inclisiran for the treatment of heterozygous familial hypercholesterolemia[J]. N Engl J Med,2020,382(16):1520-1530.

[19] Nordestgaard BG,Nicholls SJ,Langsted A,et al. Advances in lipid-lowering therapy through gene-silencing technologies[J]. Nat Rev Cardiol,2018,15(5):261-272.

[20] Asbeutah A,Asbeutah SA,Abu-Assi MA. A meta-analysis of cardiovascular outcomes in patients with hypercholesterolemia treated with inclisiran[J]. Am J Cardiol,2020,128:218-219.

[21] Landlinger C,Pouwer MG,Juno C,et al. The AT04A vaccine against proprotein convertase subtilisin/kexin type 9 reduces total cholesterol,vascular inflammation,and atherosclerosis in APOE*3Leiden.CETP mice[J]. Eur Heart J,2017,38(32):2499-2507.

[22] Wang Y,Wang J,Wang S. Comparative effectiveness of inclisiran 100,300,and 500 mg in a population with hyperlipidemia: a network meta-analysis of randomized controlled trials[J]. Am J Cardiovasc Drugs,2018,18(4):271-282.

[23] Catapano AL,Pirillo A,Norata GD. Insights from ORION studies:focus on inclisiran safety[J]. Cardiovasc Res,2021,117(1):24-26.

[24] Zijlstra LE,Trompet S,Mooijaart SP,et al. Renal impairment,cardiovascular disease,and the short-term efficacy and safety of PCSK9 targeted by inclisiran[J]. Mayo Clin Proc,2020,95(1):12-14.

[25] Stoekenbroek RM,Kallend D,Wijngaard PL,et al. Inclisiran for the treatment of cardiovascular disease:the ORION clinical development program[J]. Future Cardiol,2018,14(6):433-442.

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更新日期/Last Update: 2021-09-10