GBOU DPO Russian Medical Academy for Postgraduate Medical Education Ministry of Health, Moscow, Russian Federation.
I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russian Federation.
Cardiovasc Drugs Ther. 2021 Aug;35(4):841-852. doi: 10.1007/s10557-020-07139-x. Epub 2021 Jan 27.
An elevated plasma low-density lipoprotein cholesterol (LDL-C) level is a well-established atherosclerotic cardiovascular disease (ACSVD) risk factor. Randomized studies with statins (alone or in combination with other lipid-lowering drugs) have demonstrated their clinical efficacy in lowering LDL-C. Several classes of new, non-statin agents have been successfully studied and used (e.g., ezetimibe and inhibitors of proprotein convertase subtilisin/kexin type 9 [i-PSCK9]). However, many high ACSVD risk patients remain at a high residual cardiovascular risk, with at least 10% being statin intolerant. Bempedoic acid (ETC-1002) is a new inhibitor of cholesterol synthesis that targets ATP citrate lyase (ACL). Importantly, ETC-1002 is only converted into an active form in the liver and is free of muscle side effects.Area Covered: Mechanism of action of ETC-1002, clinical pharmacology, completed clinical studies with bempedoic acid, lipid-lowering efficacy/safety issues, and recent meta-analyses of trials with ETC-1002.Expert Opinion: ETC-1002 has been extensively studied in phase I-III clinical studies in over 4000 individuals from different patient populations (statin intolerance, familial hypercholesterolemia, and high ACSVD risk patients), ETC-1002 has been demonstrated to have moderate cholesterol-lowering efficacy and a good safety profile at a dose of 180 mg/day as a monotherapy and in combination with statins and ezetimibe. The ongoing study CLEAR Outcomes, with composite cardiovascular endpoints, will elucidate the role of bempedoic acid in the management of high ACSVD risk and statin-intolerant patients with hypercholesterolemia. Long-term safety data on bempedoic acid are needed to fully establish this agent in evidence-informed guidelines for managing of patients with dyslipidemias.
血浆低密度脂蛋白胆固醇（LDL-C）水平升高是明确的动脉粥样硬化性心血管疾病（ASCVD）危险因素。他汀类药物（单独或与其他降脂药物联合使用）的随机研究已经证实了其降低 LDL-C 的临床疗效。已经成功研究和使用了几类新型非他汀类药物，例如依折麦布和前蛋白转化酶枯草溶菌素/糜蛋白酶 9 型抑制剂（i-PCSK9）。然而，许多 ASCVD 高危患者仍然存在较高的心血管残余风险，至少有 10%的患者不耐受他汀类药物。贝美前列素（ETC-1002）是一种新型胆固醇合成抑制剂，作用靶点为三磷酸柠檬酸裂解酶（ACL）。重要的是，ETC-1002 仅在肝脏中转化为活性形式，并且没有肌肉副作用。
ETC-1002 的作用机制、临床药理学、贝美前列素已完成的临床研究、降脂疗效/安全性问题以及最近对 ETC-1002 试验的荟萃分析。
ETC-1002 已在超过 4000 名来自不同患者群体（他汀类药物不耐受、家族性高胆固醇血症和 ASCVD 高危患者）的 I-III 期临床研究中进行了广泛研究，ETC-1002 已被证明在 180mg/ 天的剂量下具有中等的降脂疗效和良好的安全性，作为单药治疗以及与他汀类药物和依折麦布联合使用。正在进行的 CLEAR Outcomes 研究将阐明贝美前列素在管理 ASCVD 高危和他汀类药物不耐受高胆固醇血症患者中的作用。需要长期的贝美前列素安全性数据，以便在血脂异常患者的循证指南中充分确立该药物的地位。
