Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia
Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia
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DOI：
10.1056/nejmoa071359
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发表时间：
2007-04-19
影响因子：
158.5
通讯作者：
Bots, Michiel L.
中科院分区：
文献类型：
--
作者：
Kastelein, John J. P.;van Leuven, Sander I.;Bots, Michiel L.
背景：Torcetrapib，一种胆固醇酯转运蛋白抑制剂，可能通过增加高密度脂蛋白（HDL）胆固醇水平来减少动脉粥样硬化性血管疾病。方法：共有850例杂合子家族性高胆固醇血症患者在基线和随访时接受B型超声检查，以测量颈动脉内膜中层厚度的变化。患者完成阿托伐他汀导入期，随后随机分配接受阿托伐他汀单药治疗或阿托伐他汀联合60 mg torcetrapib治疗2 years.Results：24个月后，在阿托伐他汀单药组，平均（+/- SD）HDL胆固醇水平为52.4 +/- 13.5 mg/dl，平均低密度脂蛋白（LDL）胆固醇水平为143.2 +/- 42.2 mg/dl，而在torcetrapib-阿托伐他汀组，分别为81.5 +/- 22.6 mg/dl和115.1 +/- 48.5 mg/dl。研究期间，与仅阿托伐他汀组相比，托塞曲匹-阿托伐他汀组的平均收缩压升高2.8 mm Hg。最大颈动脉内膜中层厚度的增加，疗效的主要指标，在仅阿托伐他汀组为0.0053 +/- 0.0028 mm/年，在托塞曲匹-阿托伐他汀组为0.0047 +/- 0.0028 mm/年（P=0.87）。次要疗效指标，即颈总动脉平均颈动脉内膜中层厚度的年变化，表明仅阿托伐他汀组每年降低0.0014 mm，而托塞曲匹-阿托伐他汀组每年增加0.0038 mm（P=0.005）。在家族性高胆固醇血症患者中，与阿托伐他汀单药相比，通过颈动脉壁厚度的联合测量评估，没有导致动脉粥样硬化进展的进一步减少，并且与颈总动脉段的疾病进展相关。尽管高密度脂蛋白胆固醇水平大幅增加，低密度脂蛋白胆固醇和甘油三酯水平大幅下降，但仍发生了这些影响。
BACKGROUND:Torcetrapib, an inhibitor of cholesteryl ester transfer protein, may reduce atherosclerotic vascular disease by increasing levels of high-density lipoprotein (HDL) cholesterol.METHODS:A total of 850 patients with heterozygous familial hypercholesterolemia underwent B-mode ultrasonography at baseline and at follow-up to measure changes in carotid intima-media thickness. The patients completed an atorvastatin run-in period and were subsequently randomly assigned to receive either atorvastatin monotherapy or atorvastatin combined with 60 mg of torcetrapib for 2 years.RESULTS:After 24 months, in the atorvastatin-only group, the mean (+/- SD) HDL cholesterol level was 52.4 +/- 13.5 mg per deciliter and the mean low-density lipoprotein (LDL) cholesterol level was 143.2 +/- 42.2 mg per deciliter, as compared with 81.5 +/- 22.6 mg per deciliter and 115.1 +/- 48.5 mg per deciliter, respectively, in the torcetrapib-atorvastatin group. During the study, average systolic blood pressure increased by 2.8 mm Hg in the torcetrapib-atorvastatin group, as compared with the atorvastatin-only group. The increase in maximum carotid intima-media thickness, the primary measure of efficacy, was 0.0053 +/- 0.0028 mm per year in the atorvastatin-only group and 0.0047 +/- 0.0028 mm per year in the torcetrapib-atorvastatin group (P=0.87). The secondary efficacy measure, annualized change in mean carotid intima-media thickness for the common carotid artery, indicated a decrease of 0.0014 mm per year in the atorvastatin-only group, as compared with an increase of 0.0038 mm per year in the torcetrapib-atorvastatin group (P=0.005).CONCLUSIONS:In patients with familial hypercholesterolemia, the use of torcetrapib with atorvastatin, as compared with atorvastatin alone, did not result in further reduction of progression of atherosclerosis, as assessed by a combined measure of carotid arterial-wall thickness, and was associated with progression of disease in the common carotid segment. These effects occurred despite a large increase in HDL cholesterol levels and a substantial decrease in levels of LDL cholesterol and triglycerides.