Cardiovascular (CV) disease remains the leading cause of death in the United States. In addition to lifestyle modifications, current guidelines primarily focus on lowering low-density lipoprotein cholesterol (LDL-C) to reduce atherosclerotic CV disease risk. However, despite aggressive management, a degree of residual risk remains, suggesting that focusing on lowering LDL-C alone may be inadequate and that other lipid parameters may need to be targeted. In patients who remain at high risk despite current pharmacologic options either because of inadequate response, elevated levels of other lipoproteins, or those who have genetic variants predisposing them to atherosclerotic CV disease, additional treatment strategies continue to be sought. One such group is the homozygous familial hypercholesterolemia population, especially those patients carrying the null low-density lipoprotein receptor mutation as they often fail to derive the same benefit from traditional LDL-C lower strategies such as statins and proprotein convertase subtilisin/kexin type 9 inhibitors that work by upregulating the LDL receptor. Emerging data also suggest that patients with increased levels of triglyceride-rich lipoproteins are also at increased risk as elevated levels are proposed to have a role in various pathways promoting atherogenesis. Angiopoietin-life protein 3 (ANGLTPL3) has recently become a target of interest because of the discovery that inhibiting its action leads to reductions in lipid parameters. Although the mechanism of action of ANGLTPL3 inhibitors is independent of the LDL receptor, their ability to significantly lower triglycerides and LDL-C make them an attractive option particularly in patients with homozygous familial hypercholesterolemia and hypertriglyceridemia. The efficacy and safety of 2 ANGLTPL3 inhibitor agents have been evaluated in clinical trials. In this review, the lipid lowering, metabolic effects, and safety are reported. Ongoing trials assessing CV outcomes as well as long-term safety data are still needed to provide a more definitive role for these agents in the overall management in these populations.

中文翻译：

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人血管生成素样蛋白 3/ANGPTL3 抗体：添加到血脂异常管理的武器库。

心血管（CV）疾病仍然是美国的主要死因。除了生活方式的改变，目前的指南主要关注降低低密度脂蛋白胆固醇 (LDL-C) 以降低动脉粥样硬化性心血管疾病的风险。然而，尽管进行了积极的管理，但仍存在一定程度的残余风险，这表明仅关注降低 LDL-C 可能是不够的，可能需要针对其他血脂参数。对于由于反应不足、其他脂蛋白水平升高或遗传变异易患动脉粥样硬化性心血管疾病的患者，尽管目前的药物选择仍处于高风险状态，但仍在寻求其他治疗策略。一个这样的群体是纯合子家族性高胆固醇血症人群，特别是那些携带无效低密度脂蛋白受体突变的患者，因为他们通常无法从传统的降低 LDL-C 策略中获得相同的益处，例如通过上调 LDL 受体起作用的他汀类药物和前蛋白转化酶枯草溶菌素/kexin 9 型抑制剂。新出现的数据还表明，富含甘油三酯的脂蛋白水平升高的患者风险也增加，因为升高的水平被认为在促进动脉粥样硬化形成的各种途径中起作用。血管生成素生命蛋白 3 (ANGLTPL3) 最近已成为人们关注的目标，因为发现抑制其作用会导致脂质参数降低。尽管 ANGLTPL3 抑制剂的作用机制与 LDL 受体无关，它们显着降低甘油三酯和 LDL-C 的能力使其成为一种有吸引力的选择，特别是在纯合子家族性高胆固醇血症和高甘油三酯血症患者中。已在临床试验中评估了 2 种 ANGLTPL3 抑制剂的疗效和安全性。在这篇综述中，报告了降脂、代谢作用和安全性。仍需要评估 CV 结果以及长期安全性数据的正在进行的试验，以便为这些药物在这些人群的整体管理中提供更明确的作用。