Role of Bempedoic Acid in Clinical Practice.
Role of Bempedoic Acid in Clinical Practice.
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DOI：
10.1007/s10557-021-07147-5
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发表时间：
2021-08
影响因子：
3.4
通讯作者：
Saseen JJ
中科院分区：
文献类型：
--
作者：
Ballantyne CM;Bays H;Catapano AL;Goldberg A;Ray KK;Saseen JJ
许多患者单独使用他汀类药物不能达到最佳的低密度脂蛋白胆固醇（LDL-C）水平;其他患者无法耐受他汀类药物治疗。其他非他汀类药物治疗选择，包括依折麦布，前蛋白转化酶枯草杆菌蛋白酶/kexin 9型抑制剂和胆汁酸螯合剂，通常是必要的，以进一步降低动脉粥样硬化性心血管疾病的风险。本综述提供了关于使用bempedoic酸降低LDL-C的实用指南，包括哪些患者可能受益的指导和治疗期间安全监测的建议。Bempedoic acid是一种新型药物，是一种通过极长链酰基辅酶A合成酶1转化为bempedoyl-CoA的前药，该酶在肝脏中高表达，但在骨骼肌中检测不到。Bempedoic acid抑制三磷酸腺苷（ATP）-柠檬酸裂解酶，该酶位于胆固醇生物合成途径中β-羟基β-甲基戊二酰-CoA还原酶上游两步。在患有动脉粥样硬化性心血管疾病或家族性杂合子高胆固醇血症或有患动脉粥样硬化性心血管疾病或家族性杂合子高胆固醇血症风险的患者中进行的临床试验中，与安慰剂相比，bempedoic acid与他汀类药物和/或依折麦布联合治疗可显著降低LDL-C、载脂蛋白B和高敏C反应蛋白。即使在服用最大耐受他汀类药物的患者中，与安慰剂相比，苯哌多酸通常耐受良好，肌肉相关症状无临床意义的增加。血清尿酸的小幅升高（平均升高0.8 mg/dL）是最值得注意的不良反应。Bempedoic acid提供了一种有效且通常耐受性良好的药物，可进一步降低服用最大耐受他汀类药物的患者的LDL-C，或管理无法服用他汀类药物的患者的LDL-C水平。目前正在CLEAR Outcomes试验中研究bempedoic acid降低主要心血管事件发生率的可能性，预计2023年将获得结果。
Many patients do not achieve optimal low-density lipoprotein cholesterol (LDL-C) levels with statins alone; others are unable to tolerate statin therapy. Additional non-statin treatment options including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bile acid sequestrants are often necessary to further reduce the risk of atherosclerotic cardiovascular disease. This review provides practical guidance as to the use of bempedoic acid to lower LDL-C and includes direction as to which patients may benefit and advice for safety monitoring during treatment. Bempedoic acid, a new class of agent, is a prodrug converted to bempedoyl-CoA by very long-chain acyl-CoA synthetase 1, an enzyme with high expression in the liver but that is undetectable in the skeletal muscle. Bempedoic acid inhibits the enzyme adenosine triphosphate (ATP)-citrate lyase, which lies two steps upstream from β-hydroxy β-methylglutaryl-CoA reductase in the cholesterol biosynthesis pathway. In clinical trials conducted in patients with or at risk for atherosclerotic cardiovascular disease or familial heterozygous hypercholesterolemia, bempedoic acid in combination with statins and/or ezetimibe significantly reduced LDL-C, apolipoprotein B, and high-sensitivity C-reactive protein compared with placebo. Bempedoic acid is generally well tolerated with no clinically meaningful increase in muscle-related symptoms relative to placebo, even in patients taking maximally tolerated statins. A small increase in serum uric acid (mean increase 0.8 mg/dL) is the most noteworthy adverse effect. Bempedoic acid provides an effective and generally well-tolerated medication to further reduce LDL-C in patients taking maximally tolerated statins or manage LDL-C levels in those who are unable to take statins. The potential for a reduced incidence of major cardiovascular events with bempedoic acid is being investigated in the CLEAR Outcomes trial, with results expected in 2023.
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影响因子：
3.7
作者：
Hoffman KB;Kraus C;Dimbil M;Golomb BA
通讯作者：
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影响因子：
24
作者：
Grundy, Scott M.;Stone, Neil J.;Wijeysundera, Duminda N.
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影响因子：
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作者：
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DOI：
10.1016/j.numecd.2017.03.001
发表时间：
2017-05-01
影响因子：
3.9
作者：
Casula, M.;Mozzanica, F.;Catapano, A. L.
通讯作者：
Catapano, A. L.
影响因子：
168.9
作者：
Baigent, C;Keech, A;Simes, J
通讯作者：
Simes, J