Department of Cardiology, Mount Sinai Beth Israel, New York, NY, USA.
Department of Internal Medicine, University of Connecticut Health Center, Farmington, CT, USA.
Ann Med. 2022 Dec;54(1):1287-1296. doi: 10.1080/07853890.2022.2059559.
Atherosclerotic heart disease is the leading cause of mortality and morbidity in the USA. Low density lipoprotein (LDL) has been the target for many hypolipidemic agents to modify atherosclerotic risk. Bempedoic acid is a novel hypolipidemic drug that inhibits the enzymatic activity of ATP citrate lyase in the cholesterol synthesis pathway. CLEAR Harmony, CLEAR Wisdom, CLEAR Tranquillity and CLEAR Serenity have shown safety and efficacy associated with long term administration of this drug. Studies have shown effectiveness in reducing LDL-C in both statin intolerant patients and in patients on maximally tolerated doses of statin. The fixed drug combination of bempedoic acid and ezetimibe in a recent phase III showed significant reduction in LDL compared with placebo, which might be a promising future for LDL reduction among statin intolerant patients. Bempedoic acid also reduced inflammatory markers like hs-CRP. Given these results, bempedoic acid alone and in combination with ezetimibe received the USA FDA approval for adults with heterozygous familial hypercholesterolaemia or established atherosclerotic cardiovascular disease. We present a comprehensive review exploring the underlying mechanism, pre-clinical studies, and clinical trials of bempedoic acid and discuss the potential future role of the drug in treating hyperlipidaemia.
动脉粥样硬化性心脏病是美国死亡和发病的主要原因。低密度脂蛋白（LDL）一直是许多降脂药物的靶点，以改变动脉粥样硬化风险。贝美前列素是一种新型的降脂药物，可抑制胆固醇合成途径中的三磷酸腺苷柠檬酸裂解酶的酶活性。CLEAR Harmony、CLEAR Wisdom、CLEAR Tranquillity 和 CLEAR Serenity 已显示出与该药物长期给药相关的安全性和疗效。研究表明，该药在他汀类药物不耐受患者和最大耐受剂量他汀类药物治疗的患者中，降低 LDL-C 均有效。最近一项 III 期固定药物联合贝美前列素和依折麦布显示与安慰剂相比，LDL 显著降低，这可能是他汀类药物不耐受患者 LDL 降低的一个有前途的未来。贝美前列素还降低了 hs-CRP 等炎症标志物。鉴于这些结果，贝美前列素单独和与依折麦布联合获得了美国 FDA 批准，用于杂合子家族性高胆固醇血症或已确诊的动脉粥样硬化性心血管疾病成人患者。我们提出了一项全面的综述，探讨了贝美前列素的潜在机制、临床前研究和临床试验，并讨论了该药物在治疗高脂血症中的潜在未来作用。
