Department of Pharmacological and Biomolecular Sciences, Università Degli Studi Di Milano, Milan, Italy.
Department of Clinical Sciences and Community Health, Università Degli Studi Di Milano, Milan, Italy.
Curr Atheroscler Rep. 2022 Oct;24(10):791-801. doi: 10.1007/s11883-022-01054-2. Epub 2022 Jul 28.
The aim of creating an orally active non-statin cholesterol-lowering drug was achieved with bempedoic acid, a small linear molecule providing both a significant low-density lipoprotein cholesterol (LDL-C) reduction and an anti-inflammatory effect by decreasing high-sensitivity C-reactive protein. Bempedoic acid antagonizes ATP citrate-lyase, a cytosolic enzyme upstream of HMGCoA reductase which is the rate-limiting step of cholesterol biosynthesis. Bempedoic acid is a pro-drug converted to its active metabolite by very-long-chain acyl-CoA synthetase 1 which is present mostly in the liver and absent in skeletal muscles. This limits the risk of myalgia and myopathy. The remit of this review is to give clinical insights on the safety and efficacy of bempedoic acid and to understand for whom it should be prescribed.
Bempedoic acid with a single daily dose (180 mg) reduces LDL-C by a mean 24.5% when given alone, by 18% when given on top of a major statin and by 38-40% when given in a fixed-dose combination with ezetimibe. Bempedoic acid does not lead to the risk of new-onset diabetes, and moderately improves the glycaemic profile. The extensive knowledge on bempedoic acid mechanism, metabolism and side effects has led to an improved understanding of the potential benefits of this agent and offers a possible alternative to cardiologists and clinical practitioners somewhat worn out today by the occurrence of the muscular side effects of statins.
通过贝匹达酸实现了具有口服活性的非他汀类降胆固醇药物的目标，该药物是一种线性小分子，通过降低高敏 C 反应蛋白，既能显著降低低密度脂蛋白胆固醇（LDL-C），又具有抗炎作用。贝匹达酸拮抗三磷酸柠檬酸裂解酶，三磷酸柠檬酸裂解酶是位于 HMGCoA 还原酶上游的胞质酶，是胆固醇生物合成的限速步骤。贝匹达酸是一种前药，通过非常长链酰基辅酶 A 合成酶 1 转化为其活性代谢物，该酶主要存在于肝脏中，而不存在于骨骼肌中。这限制了肌痛和肌病的风险。本文的目的是为贝匹达酸的安全性和疗效提供临床见解，并了解哪些患者应该使用该药物。
当单独使用时，贝匹达酸每日 1 次（180mg）可使 LDL-C 平均降低 24.5%，当与主要他汀类药物联合使用时降低 18%，当与依折麦布固定剂量联合使用时降低 38-40%。贝匹达酸不会导致新发糖尿病的风险，并且适度改善血糖谱。对贝匹达酸作用机制、代谢和副作用的广泛了解，使人们对该药物的潜在益处有了更深入的认识，并为心脏病专家和临床医生提供了一种可能的替代方案，因为他们现在因他汀类药物的肌肉副作用而感到有些疲惫。
