Departments of Cardiovascular Medicine and Cell Biology and the Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Curr Cardiol Rep. 2012 Jun;14(3):245-50. doi: 10.1007/s11886-012-0252-3.
Considerable attention focuses on the ability to develop therapeutic agents that elevate levels of high-density lipoprotein cholesterol (HDL-C). Cholesteryl ester transfer protein (CETP) inhibitors have been developed on the basis of their ability to raise HDL-C to a greater extent than lipid-modifying therapies currently used in clinical practice. Initial enthusiasm for CETP inhibition decreased as a result of adverse clinical outcomes observed with the agent torcetrapib. Elucidating off-target toxicities of torcetrapib has provided hope that other CETP inhibitors may still be of potential benefit. Evacetrapib is a novel CETP inhibitor, with favorable effects on plasma lipids and no adverse effects on blood pressure or mineralocorticoid activity in early clinical evaluation. The potential effects on cardiovascular outcomes remain to be determined.
人们非常关注开发能够提高高密度脂蛋白胆固醇 (HDL-C) 水平的治疗药物的能力。基于其提高 HDL-C 水平的能力,胆固醇酯转移蛋白 (CETP) 抑制剂已被开发出来,其作用超过了目前临床实践中使用的脂质调节疗法。由于 torcetrapib 观察到的不良临床结果,人们对 CETP 抑制的最初热情降低了。阐明 torcetrapib 的脱靶毒性为其他 CETP 抑制剂可能仍然具有潜在益处提供了希望。Evacetrapib 是一种新型的 CETP 抑制剂,在早期临床评估中对血浆脂质有有利影响,对血压或盐皮质激素活性没有不良影响。其对心血管结局的潜在影响仍有待确定。