Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Department of Cardiology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address: https://twitter.com/NickNurmohamed.
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina, USA. Electronic address: https://twitter.com/AnnMarieNavar.
J Am Coll Cardiol. 2021 Mar 30;77(12):1564-1575. doi: 10.1016/j.jacc.2020.11.079.
Adding to the foundation of statins, ezetimibe and proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i), novel, emerging low-density lipoprotein cholesterol (LDL-C)-lowering therapies are under development for the prevention of cardiovascular disease. Inclisiran, a small interfering RNA molecule that inhibits PCSK9, only needs to be dosed twice a year and has the potential to help overcome current barriers to persistence and adherence to lipid-lowering therapies. Bempedoic acid, which lowers LDL-C upstream from statins, provides a novel alternative for patients with statin intolerance. Angiopoetin-like 3 protein (ANGPTL3) inhibitors have been shown to provide potent LDL-C lowering in patients with homozygous familial hypercholesterolemia without major adverse effects as seen with lomitapide and mipomersen, and may reduce the need for apheresis. Finally, CETP inhibitors may yet be effective with the development of obicetrapib. These novel agents provide the clinician the tools to effectively lower LDL-C across the entire range of LDL-C-induced elevation of cardiovascular risk, from primary prevention and secondary prevention to null-null homozygous familial hypercholesterolemia patients.
在他汀类药物、依折麦布和前蛋白转化酶枯草溶菌素 9 抑制剂（PCSK9i）的基础上，新型、新兴的降低低密度脂蛋白胆固醇（LDL-C）疗法正在开发中，用于预防心血管疾病。Inclisiran 是一种抑制 PCSK9 的小干扰 RNA 分子，每年只需给药两次，有可能帮助克服目前坚持和遵医嘱使用降脂治疗的障碍。Bempedoic 酸可降低他汀类药物之前的 LDL-C，为不能耐受他汀类药物的患者提供了一种新的选择。血管生成素样蛋白 3 抑制剂（ANGPTL3）已被证明可在杂合子家族性高胆固醇血症患者中提供有效的 LDL-C 降低作用，且无洛美他派和米泊美生所见的主要不良反应，可能减少对血浆置换的需求。最后，CETP 抑制剂可能会随着obicetrapib 的开发而有效。这些新型药物为临床医生提供了有效降低 LDL-C 的工具，可有效降低整个 LDL-C 升高引起的心血管风险范围，从一级预防和二级预防到纯合子家族性高胆固醇血症患者。
