口服PCSK9抑制剂是否有效?

IF 5.7 2区 医学 Q1 PERIPHERAL VASCULAR DISEASE
Lale Tokgözoğlu, Angela Pirillo, Alberico L Catapano
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引用次数: 0

摘要

综述目的:降低低密度脂蛋白胆固醇(LDL-C)是降低动脉粥样硬化性心血管疾病风险的关键一步。蛋白转化酶枯草杆菌素/酮素9型(PCSK9)抑制剂是循环LDL-C水平的重要调节因子,代表了治疗高胆固醇血症的现代方法。迄今为止已批准的PCSK9治疗方法包括可注射生物制剂。在这里,我们概述了口服PCSK9抑制剂的研究现状。最近的发现:近年来已经开发了几种小分子。癸酸enlicicitide decanoate(以前称为MK-0616)已被证明可显著降低LDL-C水平,较基线降低66%,具有良好的安全性和耐受性。其与己酸钠的配制使其具有较高的生物利用度。目前正在进行几项临床试验,以评估该药物的有效性和安全性,包括一项结局试验。AZD0780是另一种口服小分子,可将LDL-C水平降低52%,可与他汀类药物联合使用。其他几个具有抑制PCSK9潜力的小分子已经被确定,其中一些已经停止了开发。口服PCSK9抑制剂在早期研究中显示出有希望的结果。如果结果研究的结果是积极的,我们将有一个安全,有效和易于使用的口服治疗。口服PCSK9抑制剂可以提供一种方便的替代注射PCSK9抑制剂,并导致更多的患者接受有效的降ldl - c治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Oral PCSK9 Inhibitors: Will They Work?

Purpose of review: Lowering low-density lipoprotein cholesterol (LDL-C) is a crucial step in reducing the risk of atherosclerotic cardiovascular disease. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), an important regulator of circulating LDL-C levels, represent a modern approach for the treatment of hypercholesterolaemia. Approved approaches targeting PCSK9 to date include injectable biologics. Here, we provide an overview of the current state of research on the development of oral PCSK9 inhibitors.

Recent findings: Several small molecules have been developed in recent years. Enlicitide decanoate (formerly known as MK-0616) has been shown to significantly reduce LDL-C levels by a maximum of 66% from baseline with a good safety and tolerability profile. Its formulation with sodium caprate enabled a higher bioavailability. Several clinical trials are currently underway to evaluate the efficacy and safety of this drug, including an outcome trial. AZD0780 is another oral small molecule that lowers LDL-C levels by 52% and can be administered on top of a statin. Several other small molecules with the potential to inhibit PCSK9 have been identified, some of which have stopped the development. Oral PCSK9 inhibitors are showing promising results in early studies. If the results of the outcome studies will be positive, we will have a safe, effective and easy-to-use oral therapy. Oral PCSK9 inhibitors could provide a convenient alternative to injectable PCSK9 inhibitors and result in a greater number of patients receiving an effective LDL-C-lowering therapy.

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来源期刊
CiteScore
9.00
自引率
3.40%
发文量
87
审稿时长
6-12 weeks
期刊介绍: The aim of this journal is to systematically provide expert views on current basic science and clinical advances in the field of atherosclerosis and highlight the most important developments likely to transform the field of cardiovascular prevention, diagnosis, and treatment. We accomplish this aim by appointing major authorities to serve as Section Editors who select leading experts from around the world to provide definitive reviews on key topics and papers published in the past year. We also provide supplementary reviews and commentaries from well-known figures in the field. An Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research.
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