Lp(a): A Rapidly Evolving Therapeutic Landscape.

IF 5.7 2区医学 Q1 PERIPHERAL VASCULAR DISEASE

Current Atherosclerosis Reports Pub Date : 2024-11-22 DOI:10.1007/s11883-024-01252-0

Khalil Anchouche, George Thanassoulis

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引用次数: 0

Abstract

Purpose of review: Elevated lipoprotein(a) (Lp[a]) is a genetically determined cardiovascular risk factor, causally linked to both atherosclerotic coronary artery disease and aortic stenosis. Elevated Lp(a) is widely prevalent, and several cardiovascular societies now recommend performing Lp(a) screening at least once in all adults. However, there are currently no approved drugs aimed specifically at lowering Lp(a). In this review, we describe several promising Lp(a)-lowering therapies in the drug development pipeline and outline what role these may have in future clinical practice.

Recent findings: Pelacarsen and olpasiran are two novel RNA-based injectable therapies which are being studied in ongoing phase 3 clinical trials, with the earliest of these to be concluded in 2025. These drugs act by degrading transcribed LPA mRNA, which would normally yield the apolipoprotein(a) constituent of Lp(a). Other candidate drugs, such as Lepodisiran, Zerlasiran, and Muvalaplin, are also in early-stage development. While there are presently no Lp(a)-lowering drugs available for routine clinical use, several promising candidates are currently under investigation. If these prove to be effective in randomized clinical trials, they will expand the cardiovascular care armamentarium and will allow clinicians to treat a presently unmitigated cardiovascular risk factor.

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脂蛋白（a）：快速演变的治疗格局。

综述目的：脂蛋白（a）（Lp[a]）升高是由基因决定的心血管风险因素，与动脉粥样硬化性冠状动脉疾病和主动脉狭窄有因果关系。脂蛋白（a）升高是一种普遍存在的现象，目前一些心血管协会建议对所有成年人至少进行一次脂蛋白（a）筛查。然而，目前还没有专门用于降低脂蛋白（a）的药物获得批准。在这篇综述中，我们介绍了几种正在研发中的有望降低脂蛋白（a）的疗法，并概述了这些疗法在未来临床实践中可能发挥的作用：Pelacarsen和olpasiran是两种基于RNA的新型注射疗法，目前正在进行3期临床试验，最早将于2025年结束。这些药物通过降解转录的 LPA mRNA 起作用，而 LPA mRNA 通常会产生脂蛋白（a）的组成成分脂蛋白（a）。其他候选药物，如 Lepodisiran、Zerlasiran 和 Muvalaplin，也处于早期开发阶段。虽然目前还没有可用于常规临床的降低脂蛋白（a）的药物，但有几种前景看好的候选药物目前正在研究中。如果这些药物在随机临床试验中证明有效，它们将扩大心血管治疗的范围，使临床医生能够治疗目前尚未缓解的心血管风险因素。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Atherosclerosis Reports 医学-

CiteScore

9.00

自引率

3.40%

发文量

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.