East Coast Institute for Research, Jacksonville, FL, USA.
Baker-Gilmour Cardiovascular Institute, Jacksonville, FL, USA.
Am J Cardiovasc Drugs. 2021 Nov;21(6):629-642. doi: 10.1007/s40256-021-00477-7. Epub 2021 May 6.
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.
低密度脂蛋白胆固醇（LDL-C）与心血管疾病（CVD）之间的关联已得到充分证实，重点是降低 LDL-C 水平以减少心血管事件。除了生活方式改变外，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剂量的他汀类药物治疗，仍有相当一部分患者无法达到 LDL-C 目标。此外，他汀类药物治疗也存在一些缺点，许多开始使用这些药物的患者因不耐受而在 1 年内停止治疗。此外，美国心脏病学会和美国心脏协会的指南都强调了获得 LDL-C 目标的重要性，因为高危人群仍然存在残留的动脉粥样硬化性 CVD 风险。尽管进行了他汀类药物治疗，但残留的心血管风险仍然存在，这凸显了评估具有有效降脂作用的治疗方法的重要性，这些方法可以与他汀类药物联合使用。人们非常关注前蛋白转化酶枯草溶菌素/kexin 9（PCSK9）途径，导致依洛尤单抗和阿利西尤单抗的开发，这两种药物是人源单克隆抗体，针对 PCSK9。这些药物已被证明可显著降低 LDL-C 水平并显著降低心血管风险，但需要每两周或每月皮下注射，这引起了人们对患者依从性的担忧。目前正在研究一种新途径，即一种合成的小干扰核糖核酸（siRNA）靶向在肝细胞中表达的 PCSK9 基因，以防止 PCSK9 的产生。这种 siRNA，依洛尤单抗，可显著降低肝脏中 PCSK9 的产生，导致 LDL-C 水平明显降低，并且当每 6 个月皮下给药时，表现出持续的药效学作用。这篇综述介绍并讨论了与依洛尤单抗相关的当前临床和科学证据。
