[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]
点击复制

新型降脂药物干扰小RNA Inclisiran最新研究进展()
分享到：

《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.

相似文献/References:

[1]胥雪莲,何川.前蛋白转化酶枯草溶菌素9与动脉粥样硬化[J].心血管病学进展,2016,(1):50.[doi:10.16806/j.cnki.issn.1004-3934.2016.01.013]
　XU Xuelian,HE Chuan.Proprotein Convertase Subtilisin/Kexin Type 9 and Atherosclerosis[J].Advances in Cardiovascular Diseases,2016,(7):50.[doi:10.16806/j.cnki.issn.1004-3934.2016.01.013]
[2]乐健 何胜虎.前蛋白转化酶枯草溶菌素9致动脉粥样硬化的机制研究进展[J].心血管病学进展,2019,(7):1000.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.009]
　YUE Jian,HE Shenghu.Advances in the mechanism of PCSK9-induced atherosclerosis[J].Advances in Cardiovascular Diseases,2019,(7):1000.[doi:10.16806/j.cnki.issn.1004-3934.2019.07.009]
[3]孟凡华 付真彦.一种新型的治疗血脂异常的干扰RNA药物Inclisiran[J].心血管病学进展,2021,(2):167.[doi:10.16806/j.cnki.issn.1004-3934.2021.02.018]
　MENG Fanhua,FU Zhenyan.Inclisiran, A New Small Interfering RNA Drug for the Treatment of Dyslipidemia[J].Advances in Cardiovascular Diseases,2021,(7):167.[doi:10.16806/j.cnki.issn.1004-3934.2021.02.018]
[4]刘力黎 陈诚 张丽敏.血脂水平与心房颤动相关性研究进展[J].心血管病学进展,2021,(6):539.[doi:10.16806/j.cnki.issn.1004-3934.2021.06.015]
　LIU Lili,CHEN Cheng,ZHANG Limin.Serum Lipid Level and Atrial Fibrillation[J].Advances in Cardiovascular Diseases,2021,(7):539.[doi:10.16806/j.cnki.issn.1004-3934.2021.06.015]
[5]袁荣辉 白春林.贝派地酸降脂疗效及安全性的研究进展[J].心血管病学进展,2021,(9):809.[doi:10.16806/j.cnki.issn.1004-3934.2021.09.000]
　(.Shanxi Medical University,Taiyuan 0000,Shanxi,et al.YUAN Ronghui1,BAI Chunlin2[J].Advances in Cardiovascular Diseases,2021,(7):809.[doi:10.16806/j.cnki.issn.1004-3934.2021.09.000]
[6]肖明瑛 苏冠华.PCSK9抑制剂多效性研究进展[J].心血管病学进展,2022,(2):124.[doi:10.16806/j.cnki.issn.1004-3934.2022.02.008]
　XIAO MingyingSU Guanhua.Pleiotropic Effects of PCSK9 Inhibitors[J].Advances in Cardiovascular Diseases,2022,(7):124.[doi:10.16806/j.cnki.issn.1004-3934.2022.02.008]
[7]王兰 叶玉兰 宁明安 张迪 尚粉青.血清PCSK9水平与PCI后冠状动脉病变再进展的关系研究[J].心血管病学进展,2022,(7):667.[doi:10.16806/j.cnki.issn.1004-3934.2022.07.000]
　WANG Lan,YE Yulan,NING Mingan,et al.Correlation Analysis Between Serum PCSK9 Level and Coronary Artery Pathological ?Progression After PCI[J].Advances in Cardiovascular Diseases,2022,(7):667.[doi:10.16806/j.cnki.issn.1004-3934.2022.07.000]
[8]许晓宇 唐炯 郑甲林.PCSK9对血管内皮功能影响的研究进展[J].心血管病学进展,2023,(6):551.[doi:10.16806/j.cnki.issn.1004-3934.2023.06.016]
　XU Xiaoyu,TANG Jiong,ZHENG Jialin.Research Progress on the Effects of PCSK9 on Vascular Endothelial Function[J].Advances in Cardiovascular Diseases,2023,(7):551.[doi:10.16806/j.cnki.issn.1004-3934.2023.06.016]
[9]黄橙 李波 李志勇 陈紫君.过低LDL-C在动脉粥样硬化性心血管疾病中潜在风险循证学证据[J].心血管病学进展,2023,(11):1041.[doi:10.16806/j.cnki.issn.1004-3934.2023.11.019]
　Huang Cheng,Li Bo,Li Zhiyong,et al.The Evidence of the Potential Risk of Excessively Low Levels of LDL-C in ASCVD[J].Advances in Cardiovascular Diseases,2023,(7):1041.[doi:10.16806/j.cnki.issn.1004-3934.2023.11.019]
[10]李开炜 彭汶婷 祝烨.降脂药物与认知功能下降的研究进展[J].心血管病学进展,2024,(3):220.[doi:10.16806/j.cnki.issn.1004-3934.2024.03.007]
　LI Kaiwei,PENG Wenting,ZHU Ye.Lipid-Lowering Drugs and Cognitive Function Decline[J].Advances in Cardiovascular Diseases,2024,(7):220.[doi:10.16806/j.cnki.issn.1004-3934.2024.03.007]
[11]李艳茹,白世茹,李如意,等.PCSK9抑制剂在血脂代谢中的研究进展[J].心血管病学进展,2020,(7):729.[doi:10.16806/j.cnki.issn.1004-3934.2020.07.014]
　LI Yanru,BAI Shiru,LI Ruyi,et al.PCSK9 Inhibitors in Lipid Metabolism[J].Advances in Cardiovascular Diseases,2020,(7):729.[doi:10.16806/j.cnki.issn.1004-3934.2020.07.014]
[12]王申仪 阳军.基于RNA疗法在动脉粥样硬化性心血管疾病血脂管理的研究进展[J].心血管病学进展,2021,(4):369.[doi:10.16806/j.cnki.issn.1004-3934.2021.04.019]
　Wang Shenyi,Yang Jun.Era of RNA-based Therapies in Lipid Management of?oronary Atherosclerotic Cardiovascular Disease[J].Advances in Cardiovascular Diseases,2021,(7):369.[doi:10.16806/j.cnki.issn.1004-3934.2021.04.019]
[13]刘杨 陈明.冠心病的治疗新方向——PCSK9抑制剂[J].心血管病学进展,2021,(9):820.[doi:10.16806/j.cnki.issn.1004-3934.2021.09.000]
　New Direction of Coronary Heart Disease TreatmentPCSK9 Inhibitors.E-mailchenmingcq77@163.com[J].Advances in Cardiovascular Diseases,2021,(7):820.[doi:10.16806/j.cnki.issn.1004-3934.2021.09.000]

更新日期/Last Update: 2021-09-10