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降脂治疗:超越他汀类药物的时代。

Lipid Lowering Therapy: An Era Beyond Statins.

机构信息

Sumy State University, Toufik's World Medical Association, Sumy, Sumy Oblast, Ukraine.

Nishtar Medical University, Nishtar Rd, Gillani Colony, Multan, Punjab, Pakistan.

出版信息

Curr Probl Cardiol. 2022 Dec;47(12):101342. doi: 10.1016/j.cpcardiol.2022.101342. Epub 2022 Jul 31.

Abstract

Dyslipidemia, specifically elevated low-density lipoprotein (LDL) cholesterol levels, causes atherosclerotic cardiovascular disease (ASCVD) and increases the risk of myocardial infarction and stroke. Statins, a class of drugs that exert their effects by inhibiting HMG-CoA reductase, a key enzyme in the synthesis of cholesterol, have been the mainstay of therapy for the primary prevention of cardiovascular disease and lipids reduction. Statins are associated with side effects, most commonly myopathy and myalgias, despite their proven efficacy. This review explores non-statin lipid-lowering therapies and examines recent advances and emerging research. Over the previous decades, several lipid-lowering therapies, both as monotherapy and adjuncts to statin therapy and lipid-targeting gene therapy, have emerged, thus redefining how we treat dyslipidemia. These drugs include Bile acids sequestrants, Fibrates, Nicotinic acid, Ezetimibe, Bempedoic acid, Volanesoren, Evinacumab, and the PCSK 9 Inhibitors Evolocumab and Alirocumab. Emerging gene-based therapy includes Small interfering RNAs, Antisense oligonucleotides, Adeno-associated virus vectors, CRISPR/Cas9 based therapeutics, and Non-coding RNA therapy. Of all these therapies, Bempedoic acid works most like statins by working through a similar pathway to decrease cholesterol levels. However, it is not associated with myopathy. Overall, although statins continue to be the gold standard, non-statin therapies are set to play an increasingly important role in managing dyslipidemia.

摘要

血脂异常,特别是低密度脂蛋白(LDL)胆固醇水平升高,会导致动脉粥样硬化性心血管疾病(ASCVD),增加心肌梗死和中风的风险。他汀类药物是一类通过抑制 HMG-CoA 还原酶(胆固醇合成的关键酶)发挥作用的药物,一直是心血管疾病一级预防和降低血脂的主要治疗方法。尽管他汀类药物已被证明有效,但它们仍与副作用有关,最常见的是肌病和肌痛。本综述探讨了非他汀类降脂治疗方法,并考察了最新进展和新兴研究。在过去几十年中,出现了几种降脂治疗方法,包括单药治疗以及作为他汀类药物治疗和靶向脂质的基因治疗的辅助治疗,从而重新定义了我们治疗血脂异常的方法。这些药物包括胆汁酸螯合剂、贝特类、烟酸、依折麦布、贝马布酯、Volanesoren、依洛尤单抗和 PCSK9 抑制剂依洛尤单抗和阿利西尤单抗。新兴的基于基因的治疗方法包括小干扰 RNA、反义寡核苷酸、腺相关病毒载体、基于 CRISPR/Cas9 的治疗方法和非编码 RNA 治疗。在所有这些治疗方法中,贝马布酯通过与他汀类药物相似的途径降低胆固醇水平,最类似于他汀类药物。然而,它与肌病无关。总的来说,尽管他汀类药物仍然是金标准,但非他汀类药物治疗方案将在管理血脂异常方面发挥越来越重要的作用。

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