Eyvazian Vaughn A, Frishman William H
From the *Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, CA; and †Department of Medicine, New York Medical College/Westchester Medical Center, Valhalla, NY.
Cardiol Rev. 2017 Mar/Apr;25(2):43-52. doi: 10.1097/CRD.0000000000000137.
Evacetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that has been recently studied as a cholesterol modifying agent to reduce cardiovascular risk and mortality in high risk cardiovascular disease patients. Evacetrapib acts to decrease lipid exchange through CETP inhibition. CETP acts to transfer cholesteryl esters from high-density lipoprotein-cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) and very-low-density lipoprotein (VLDL-C). HDL-C is involved in reverse cholesterol transport and its blood levels have been shown to be inversely correlated with cardiovascular risk. Thus, a pharmacologic agent that can elevate HDL-C has been seen as an exciting area of research. In recent studies, evacetrapib was shown to be safe and efficacious. It produced an increase in HDL-C up to 128% and a 35% decrease in LDL-C, in comparison to placebo. In addition, evacetrapib was also shown to be more potent than previous CETP inhibitors. HDL-C particles treated with evacetrapib remained functional and had improved cholesterol efflux. A previously studied CETP inhibitor, torcetrapib, exhibited side effects of hyperaldosteronism, manifesting in electrolyte disturbances, and hypertension. These detrimental effects were not seen with evacetrapib. Recently, the results of evacetrapib's phase III ACCELERATE trial showed no significant reduction in major adverse cardiovascular events or mortality, and the drug will not be marketed. Although beneficial cholesterol effects were seen with this drug, more needs to be known to understand what role, if any, evacetrapib has in the reduction of cardiovascular risk.
依折麦布是一种胆固醇酯转移蛋白（CETP）抑制剂，最近作为一种胆固醇调节药物进行了研究，用于降低高危心血管疾病患者的心血管风险和死亡率。依折麦布通过抑制CETP来减少脂质交换。CETP的作用是将胆固醇酯从高密度脂蛋白胆固醇（HDL-C）转移到低密度脂蛋白胆固醇（LDL-C）和极低密度脂蛋白（VLDL-C）。HDL-C参与逆向胆固醇转运，其血液水平已被证明与心血管风险呈负相关。因此，一种能够升高HDL-C的药物被视为一个令人兴奋的研究领域。在最近的研究中，依折麦布被证明是安全有效的。与安慰剂相比，它使HDL-C升高了128%，LDL-C降低了35%。此外，依折麦布还被证明比以前的CETP抑制剂更有效。用依折麦布处理的HDL-C颗粒仍具有功能，胆固醇流出得到改善。一种先前研究的CETP抑制剂托彻普贝表现出醛固酮增多症的副作用，表现为电解质紊乱和高血压。依折麦布没有出现这些有害影响。最近，依折麦布的III期ACCELERATE试验结果显示，主要不良心血管事件或死亡率没有显著降低，该药物将不会上市。尽管这种药物对胆固醇有有益作用，但仍需要更多了解依折麦布在降低心血管风险中所起的作用（如果有作用的话）。
