The association between low-density cholesterol (LDL-C) and cardiovascular disease (CVD) is well-established, with an emphasis on lowering LDL-C levels to reduce cardiovascular events. Statin therapy has been the traditional treatment for LDL-C reduction, in addition to lifestyle modifications, but studies have shown that a substantial proportion of patients does not reach target LDL-C goals despite receiving maximally tolerated statin medications. Additionally, statin therapy is associated with a few shortcomings as many patients initiated on these medications discontinue treatment within 1 year because of lack of tolerability. Furthermore, guidelines from both the American College of Cardiology and the American Heart Association highlight the importance of obtaining LDL-C goals because of the residual atherosclerotic CVD risk that remains in high-risk populations. That the residual cardiovascular risk remains despite statin therapy highlights the importance of evaluating therapeutic approaches that possess effective lipid lowering that can be used adjunctively with statins. Much focus has been directed towards the proprotein convertase subtilisin/kexin type 9 (PCSK9) pathway, leading to the development of evolocumab and alirocumab, two human monoclonal antibodies directed against PCSK9. These agents have been shown to markedly decrease LDL-C levels and significantly reduce cardiovascular risk, but the need for biweekly or monthly subcutaneous injections has generated concerns for patient compliance. A new pathway is being studied in which a synthetic small interfering ribonucleic acid (siRNA) targets the PCSK9 gene expressed in hepatocytes to prevent PCSK9 production. The siRNA, inclisiran sodium, significantly reduces hepatic production of PCSK9, causing a marked reduction in LDL-C levels, and exhibits sustained pharmacodynamic effects when dosed subcutaneously every 6 months. This review presents and discusses the current clinical and scientific evidence pertaining to inclisiran sodium.

低密度胆固醇 (LDL-C) 与心血管疾病 (CVD) 之间的关联已经确立，重点是降低 LDL-C 水平以减少心血管事件。除了改变生活方式外，他汀类药物治疗一直是降低 LDL-C 的传统治疗方法，但研究表明，尽管接受了最大耐受性的他汀类药物治疗，仍有相当一部分患者未达到 LDL-C 目标。此外，他汀类药物治疗也存在一些缺点，因为许多开始使用这些药物的患者在 1 年内由于缺乏耐受性而停止治疗。此外，美国心脏病学会和美国心脏协会的指南都强调了达到 LDL-C 目标的重要性，因为高危人群仍然存在动脉粥样硬化 CVD 风险。尽管他汀类药物治疗，残余心血管风险仍然存在，这凸显了评估可与他汀类药物联合使用的有效降脂治疗方法的重要性。很多焦点都集中在前蛋白转化酶枯草杆菌蛋白酶 / kexin 9 型 (PCSK9) 途径上，导致开发了 evolocumab 和 alirocumab，这两种针对 PCSK9 的人单克隆抗体。这些药物已被证明可显着降低 LDL-C 水平并显着降低心血管风险，但是每两周或每月一次皮下注射的需要引起了患者依从性的担忧。正在研究一种新途径，其中合成的小干扰核糖核酸 (siRNA) 靶向PCSK9基因在肝细胞中表达以阻止 PCSK9 的产生。siRNA inclisiran sodium 可显着降低 PCSK9 的肝脏生成，导致 LDL-C 水平显着降低，并且每 6 个月皮下给药时表现出持续的药效学作用。本综述介绍并讨论了有关 inclisiran 钠的当前临床和科学证据。