Bellino Michele, Galasso Gennaro, Silverio Angelo, Tedeschi Michele, Formisano Ciro, Romei Stefano, Esposito Luca, Cancro Francesco Paolo, Vassallo Maria Giovanna, Accarino Giulio, Verdoia Monica, Di Muro Francesca Maria, Vecchione Carmine, De Luca Giuseppe
Department of Medicine, Surgery and Dentistry, University of Salerno, 84081 Baronissi, Italy.
Division of Cardiology, Ospedale Degli Infermi, ASL Biella, 13900 Biella, Italy.
J Clin Med. 2023 Apr 18;12(8):2922. doi: 10.3390/jcm12082922.
Current research on cardiovascular prevention predominantly focuses on risk-stratification and management of patients with coronary artery disease (CAD) to optimize their prognosis. Several basic, translational and clinical research efforts aim to determine the etiological mechanisms underlying CAD pathogenesis and to identify lifestyle-dependent metabolic risk factors or genetic and epigenetic parameters responsible for CAD occurrence and/or progression. A log-linear association between the absolute exposure of LDL cholesterol (LDL-C) and the risk of atherosclerotic cardio-vascular disease (ASCVD) was well documented over the year. LDL-C was identified as the principal enemy to fight against, and soluble proprotein convertase subtilisin kexin type 9 (PCSK9) was attributed the role of a powerful regulator of blood LDL-C levels. The two currently available antibodies (alirocumab and evolocumab) against PCSK9 are fully human engineered IgG that bind to soluble PCSK9 and avoid its interaction with the LDLR. As documented by modern and dedicated "game-changer" trials, antibodies against soluble PCSK9 reduce LDL-C levels by at least 60 percent when used alone and up to 85 percent when used in combination with high-intensity statins and/or other hypolipidemic therapies, including ezetimibe. Their clinical indications are well established, but new areas of use are advocated. Several clues suggest that regulation of PCSK9 represents a cornerstone of cardiovascular prevention, partly because of some pleiotropic effects attributed to these newly developed drugs. New mechanisms of PCSK9 regulation are being explored, and further efforts need to be put in place to reach patients with these new therapies. The aim of this manuscript is to perform a narrative review of the literature on soluble PCSK9 inhibitor drugs, with a focus on their indications and clinical impact.
目前关于心血管疾病预防的研究主要集中在对冠状动脉疾病（CAD）患者进行风险分层和管理，以优化其预后。多项基础、转化和临床研究致力于确定CAD发病机制的病因学机制，并识别与生活方式相关的代谢危险因素或导致CAD发生和/或进展的遗传和表观遗传参数。多年来，低密度脂蛋白胆固醇（LDL-C）的绝对暴露量与动脉粥样硬化性心血管疾病（ASCVD）风险之间的对数线性关联已得到充分证实。LDL-C被确定为主要的防治目标，而前蛋白转化酶枯草溶菌素9型（PCSK9）被认为是血液中LDL-C水平的有力调节因子。目前两种可用的抗PCSK9抗体（阿利西尤单抗和依洛尤单抗）是完全人源化的工程IgG，它们与可溶性PCSK9结合，避免其与低密度脂蛋白受体（LDLR）相互作用。正如现代专门的“变革性”试验所证明的，抗可溶性PCSK9抗体单独使用时可使LDL-C水平降低至少60%，与高强度他汀类药物和/或其他降血脂疗法（包括依折麦布）联合使用时可降低多达85%。它们的临床适应症已得到充分确立，但也有人主张拓展新的应用领域。有几条线索表明，PCSK9的调节是心血管疾病预防的基石，部分原因是这些新开发药物具有一些多效性作用。目前正在探索PCSK9调节的新机制，还需要进一步努力，以便让这些新疗法惠及患者。本文的目的是对可溶性PCSK9抑制剂药物的文献进行叙述性综述，重点关注其适应症和临床影响。
