Inclisiran作为枯草杆菌蛋白转化酶/Kexin 9型（PCSK9）的siRNA抑制剂过去，现在和未来。

IF 2.8 4区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

American Journal of Cardiovascular Drugs Pub Date : 2024-12-20 DOI:10.1007/s40256-024-00712-x

Taha Mansoor, Bassam Hamid Rao, Kartik Gupta, Sachin S Parikh, Dmitry Abramov, Anurag Mehta, Mahmoud Al Rifai, Salim S Virani, Vijay Nambi, Abdul Mannan Khan Minhas, Santhosh K G Koshy

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引用次数: 0

摘要

降低低密度脂蛋白胆固醇（LDL-C）水平已被证明可以降低发生动脉粥样硬化性心血管疾病（ASCVD）的风险。他汀类药物是降低LDL-C治疗的基础，在没有达到目标LDL-C水平或由于他汀类药物的不良反应不耐受的情况下，与其他非他汀类药物一起使用。2003年，蛋白转化酶枯草杆菌素/酮素9型（PCSK9）系统在促进LDL-C水平升高中的作用的发现，为实现目标LDL-C的药物开发开辟了新的途径。2021年，一种靶向PCSK9的小干扰核糖核酸（siRNA）分子inclisiran获得了美国食品和药物管理局（FDA）的批准。Inclisiran已经证明了LDL-C的有效降低，例如在ORION-9、ORION-10和ORION-11的大型三期试验中，它分别实现了39.7%、52.3%和49.9%的LDL-C降低。本文讨论了inclisiran目前的临床证据和正在进行的临床研究，并分析了PCSK9抑制发展的其他领域。

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Inclisiran as a siRNA Inhibitor of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); Past, Present, and Future.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C. In 2021, inclisiran, a small interfering ribonucleic acid (siRNA) molecule targeting PCSK9 was approved by the Food and Drug Administration (FDA). Inclisiran has demonstrated effective reductions of LDL-C, such as in the large phase-3 ORION-9, ORION-10, and ORION-11 trials in which it achieved LDL-C reductions of 39.7%, 52.3%, and 49.9%, respectively. This review discusses the current clinical evidence and ongoing clinical studies of inclisiran as well as analyzes other areas of PCSK9 inhibition development.

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来源期刊

American Journal of Cardiovascular Drugs 医学-心血管系统

CiteScore

6.70

自引率

3.30%

发文量

审稿时长

>12 weeks

期刊介绍： Promoting rational therapy within the discipline of cardiology, the American Journal of Cardiovascular Drugs covers all aspects of the treatment of cardiovascular disorders, particularly the place in therapy of newer and established agents. Via a program of reviews and original clinical research articles, the journal addresses major issues relating to treatment of these disorders, including the pharmacology, efficacy and adverse effects of the major classes of drugs; information on newly developed drugs and drug classes; the therapeutic implications of latest research into the aetiology of cardiovascular disorders; and the practical management of specific clinical situations. The American Journal of Cardiovascular Drugs offers a range of additional enhanced features designed to increase the visibility, readership and educational value of the journal’s content. Each article is accompanied by a Key Points summary, giving a time-efficient overview of the content to a wide readership. Articles may be accompanied by plain language summaries to assist patients, caregivers and others in understanding important medical advances. The journal also provides the option to include various other types of enhanced features including slide sets, videos and animations. All enhanced features are peer reviewed to the same high standard as the article itself. Peer review is conducted using Editorial Manager®, supported by a database of international experts. This database is shared with other Adis journals.