Can we revive CETP-inhibitors for the prevention of cardiovascular disease?

IF 3.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current opinion in lipidology Pub Date : 2022-12-01 DOI:10.1097/MOL.0000000000000854

Stephen J Nicholls, Kausik K Ray, Adam J Nelson, John J P Kastelein

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引用次数: 4

Abstract

Purpose of review: To review recent developments in the field of cholesteryl ester transfer protein (CETP) inhibition from clinical trials and genomic analyses which have the potential to impact future clinical programs.

Recent findings: CETP plays an important role in remodelling of lipoproteins. A large body of evidence suggests that the presence of low CETP activity should have favourable effects on lipid profiles and cardiovascular risk. However, a number of clinical development programs of pharmacological CETP inhibitors have been disappointing with reports of toxicity and clinical futility. These findings have led many to consider abandoning CETP inhibition as a potential strategy for cardiovascular prevention. However, recent observations from genomic analyses and post hoc observations of prior clinical trials have given greater insights into the potential relationship between CETP inhibition and cardiovascular risk. This has highlighted the importance of lowering levels of atherogenic lipoproteins.

Summary: These findings provide a pathway for ongoing clinical development of CETP inhibitors, where the potential to play an important role in the prevention of cardiovascular disease may still be possible. The lessons learned and pathway forward for new CETP inhibitors will be reviewed.

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我们能否重新启用cetp抑制剂来预防心血管疾病?

综述目的:综述最近在抑制胆固醇酯转移蛋白(CETP)方面的研究进展，包括临床试验和基因组分析，这些研究对未来的临床计划有潜在的影响。最近研究发现:CETP在脂蛋白重塑中起重要作用。大量证据表明，低CETP活性的存在对脂质谱和心血管风险有有利影响。然而，药理学CETP抑制剂的一些临床开发项目令人失望，报告毒性和临床无效。这些发现导致许多人考虑放弃CETP抑制作为心血管预防的潜在策略。然而，最近来自基因组分析的观察和对先前临床试验的事后观察，对CETP抑制与心血管风险之间的潜在关系有了更深入的了解。这突出了降低致动脉粥样硬化脂蛋白水平的重要性。总结:这些发现为正在进行的CETP抑制剂的临床开发提供了一条途径，在心血管疾病预防中发挥重要作用的潜力仍然是可能的。本文将回顾新的CETP抑制剂的经验教训和发展方向。

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 opinion in lipidology 医学-内分泌学与代谢

CiteScore

6.70

自引率

4.50%

发文量

审稿时长

6-12 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Lipidology offers expert evaluation on a wide range of topics from six key disciplines including nutrition and metabolism, genetics and molecular biology, and hyperlipidaemia and cardiovascular disease. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by a section of Bimonthly Updates, which deliver an insight into new developments at the cutting edge of the disciplines covered in the journal.