From the Division of Molecular Medicine, Department of Medicine, Columbia University, New York (A.R.T.); and Departments of Genetics and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (D.J.R.)
From the Division of Molecular Medicine, Department of Medicine, Columbia University, New York (A.R.T.); and Departments of Genetics and Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (D.J.R.).
Circ Res. 2018 Jan 5;122(1):106-112. doi: 10.1161/CIRCRESAHA.117.311978. Epub 2017 Oct 10.
The development of CETP (cholesteryl ester transfer protein) inhibitors has had a long and difficult course with 3 compounds failing in phase III clinical trials. Finally, the REVEAL (Randomized Evaluation of the Effects of Anacetrapib through Lipid modification) trial has shown that the CETP inhibitor anacetrapib decreased coronary heart disease when added to statin therapy. Although the result is different to earlier studies, this is likely related to the size and duration of the trial. The benefit of anacetrapib seems to be largely explained by lowering of non-HDL-C (high-density lipoprotein cholesterol), rather than increases in HDL-C. Although the magnitude of benefit for coronary heart disease appeared to be moderate, in part this may have reflected aspects of the trial design. Anacetrapib treatment was associated with a small increase in blood pressure, but was devoid of major side effects and was also associated with a small reduction in diabetes mellitus. Treatment with CETP inhibitors, either alone or in combination with statins, could provide another option for patients with coronary disease who require further reduction in LDL (low-density lipoprotein) and non-HDL-C.
CETP（胆固醇酯转移蛋白）抑制剂的开发经历了漫长而艰难的过程，已有 3 种化合物在 III 期临床试验中失败。最后，REVEAL（通过脂质修饰随机评估 Anacetrapib 的效果）试验表明，CETP 抑制剂 Anacetrapib 可降低他汀类药物治疗时的冠心病风险。尽管这一结果与早期研究不同，但这可能与试验的规模和持续时间有关。Anacetrapib 的益处似乎主要归因于非高密度脂蛋白胆固醇（高密度脂蛋白胆固醇）的降低，而不是高密度脂蛋白胆固醇的升高。虽然冠心病的获益幅度似乎适中，但部分原因可能反映了试验设计的各个方面。Anacetrapib 治疗与血压略有升高有关，但没有重大副作用，也与糖尿病发病率略有降低有关。CETP 抑制剂单独或与他汀类药物联合治疗，可能为需要进一步降低 LDL（低密度脂蛋白）和非高密度脂蛋白胆固醇的冠心病患者提供另一种选择。
