Familial hypercholesterolemia (FH), an autosomal dominant disorder of LDL metabolism that is characterized by elevated LDL cholesterol, is commonly encountered in patients with atherosclerotic coronary heart disease. Combinations of cholesterol lowering therapies are often used to lower LDL cholesterol in patients with familial hypercholesterolemia; however, current treatment goals for LDL cholesterol are rarely achieved in patients with homozygous FH, and are difficult to achieve in patients with heterozygous FH. Therapies that lower LDL cholesterol through LDL receptor-mediated mechanisms have thus far been largely ineffective in patients with homozygous FH, particularly in those with negligible (<2%) LDL receptor activity. Among patients with heterozygous FH who were at very high risk for atherosclerotic cardiovascular disease events, combined therapy consisting of a high dose of high-intensity statin, ezetimibe and proprotein convertase subtilisin kinexin (PCSK9) inhibitor failed to lower LDL cholesterol to minimal acceptable goals in more than 50%. This article provides an overview of available and emerging treatments that lower LDL cholesterol in adult patients with homozygous FH and heterozygous FH. A framework is provided for the use of angiopoietin like 3 protein (ANGPTL3) inhibitors in the treatment of homozygous FH and heterozygous FH.

中文翻译：

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用于治疗家族性高胆固醇血症的现有和新兴疗法。

家族性高胆固醇血症 (FH) 是一种以 LDL 胆固醇升高为特征的常染色体显性低密度脂蛋白代谢疾病，常见于动脉粥样硬化性冠心病患者。降低胆固醇疗法的组合通常用于降低家族性高胆固醇血症患者的低密度脂蛋白胆固醇；然而，目前对 LDL 胆固醇的治疗目标在纯合子 FH 患者中很少达到，而在杂合子 FH 患者中很难达到。迄今为止，通过 LDL 受体介导的机制降低 LDL 胆固醇的疗法在纯合 FH 患者中基本上是无效的，特别是在那些 LDL 受体活性可忽略不计（<2%）的患者中。在动脉粥样硬化性心血管疾病事件风险极高的杂合 FH 患者中，由高剂量高强度他汀类药物、依折麦布和前蛋白转化酶枯草杆菌蛋白酶 (PCSK9) 抑制剂组成的联合治疗未能将 LDL 胆固醇降低至 50% 以上的最低可接受目标。本文概述了降低纯合子 FH 和杂合子 FH 成年患者 LDL 胆固醇的现有和新兴治疗方法。提供了使用血管生成素样 3 蛋白 (ANGPTL3) 抑制剂治疗纯合 FH 和杂合 FH 的框架。本文概述了降低纯合子 FH 和杂合子 FH 成年患者 LDL 胆固醇的现有和新兴治疗方法。提供了使用血管生成素样 3 蛋白 (ANGPTL3) 抑制剂治疗纯合 FH 和杂合 FH 的框架。本文概述了降低纯合子 FH 和杂合子 FH 成年患者 LDL 胆固醇的现有和新兴治疗方法。提供了使用血管生成素样 3 蛋白 (ANGPTL3) 抑制剂治疗纯合 FH 和杂合 FH 的框架。