Bagdade John, Barter Philip, Quiroga Carmen, Alaupovic Pierre
Community Health Clinics of Lane County, Eugene, Oregon.
Heart Research Institute, Sydney, Australia.
Am J Cardiol. 2017 Jun 1;119(11):1753-1756. doi: 10.1016/j.amjcard.2017.02.049. Epub 2017 Mar 18.
In the ILLUMINATE Trial, treatment with the cholesteryl ester transfer protein inhibitor torcetrapib resulted in a significant increase in both atherosclerotic cardiovascular disease events and total mortality which was not explained by changes in the routinely measured plasma lipids. To determine whether alterations in lipoproteins defined by their apoprotein content that are not estimated with conventional laboratory methods contributed to these unexpected events, we measured the apoB- and apoA-containing subclasses in a subgroup of ILLUMINATE participants. We find that torcetrapib treatment significantly increased the high-density lipoprotein subclasses LpA-I and LpA-I:A-II equally (p <0.0001) and the apoC-III content of high-density lipoprotein (p <0.001) without altering the apoB-containing subclasses. In conclusion, these findings provide further evidence that the untoward effects of torcetrapib were attributable to off-target effects and not related to disturbances in lipoprotein transport.
在ILLUMINATE试验中，使用胆固醇酯转运蛋白抑制剂托彻普治疗导致动脉粥样硬化性心血管疾病事件和总死亡率显著增加，而常规测量的血浆脂质变化无法解释这一现象。为了确定常规实验室方法未评估的、由载脂蛋白含量定义的脂蛋白改变是否导致了这些意外事件，我们在ILLUMINATE试验的一个亚组参与者中测量了含载脂蛋白B和载脂蛋白A的亚类。我们发现，托彻普治疗使高密度脂蛋白亚类LpA-I和LpA-I:A-II同等程度地显著增加（p<0.0001），并使高密度脂蛋白的载脂蛋白C-III含量增加（p<0.001），而含载脂蛋白B的亚类没有改变。总之，这些发现进一步证明，托彻普的不良作用归因于脱靶效应，而非与脂蛋白转运紊乱有关。
