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PCSK9 抑制剂之战:依洛尤单抗与当前单克隆抗体抑制剂治疗相比如何?患者选择的考虑因素。

PCSK9 Inhibitor Wars: How Does Inclisiran Fit in with Current Monoclonal Antibody Inhibitor Therapy? Considerations for Patient Selection.

机构信息

Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.

German Center for Cardiovascular Research (DZHK), partner site Hamburg/Kiel/Luebeck, Hamburg, Germany.

出版信息

Curr Cardiol Rep. 2022 Nov;24(11):1657-1667. doi: 10.1007/s11886-022-01782-6. Epub 2022 Sep 10.

Abstract

PURPOSE OF REVIEW

Treatment of dyslipidemia represents one of the most crucial strategies to reduce risk of atherosclerotic cardiovascular (CV) disease (ASCVD). In this review, we critically summarize our knowledge on emerging cholesterol-lowering therapy, targeting PCSK9, paying particular attention on treatment allocation of two drug groups, currently available for clinical use, namely, anti-PCSK9 monoclonal antibodies (mAbs) and inclisiran, a first-in-class small interfering RNA against PCSK9.

RECENT FINDINGS

Although both drug classes show a pronounced, but fairly similar reduction in LDL-cholesterol, their long-term safety is still unknown. Compared to mAbs, inclisiran has a more favorable dosing regimen with biannual application that might improve therapeutic adherence significantly. However, a CV outcome trial (CVOT) for inclisiran is still missing. If inclisiran will be safe and effective in ongoing/future CVOTs, it has a huge potential to overcome medication non-compliance, thereby providing a powerful therapeutic option to decrease the burden of ASCVD.

摘要

目的综述

治疗血脂异常是降低动脉粥样硬化性心血管疾病(ASCVD)风险的最重要策略之一。在这篇综述中,我们批判性地总结了我们对新兴降脂治疗的认识,重点关注针对 PCSK9 的治疗分配,特别关注目前可用于临床的两类药物,即抗 PCSK9 单克隆抗体(mAbs)和inclisiran,这是一种针对 PCSK9 的新型小干扰 RNA。

最新发现

虽然这两类药物都能显著降低 LDL 胆固醇,但它们的长期安全性仍不清楚。与 mAbs 相比,inclisiran 的给药方案更有利,每半年应用一次,可能会显著提高治疗依从性。然而,inclisiran 的心血管结局试验(CVOT)仍然缺失。如果 inclisiran 在正在进行/未来的 CVOT 中是安全有效的,它将有很大的潜力克服药物依从性差的问题,从而为降低 ASCVD 负担提供一种强大的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266f/9729136/1ed6108ef145/11886_2022_1782_Fig1_HTML.jpg

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