Tardif Jean-Claude, Grégoire Jean, L'Allier Philippe L, Anderson Todd J, Bertrand Olivier, Reeves Francois, Title Lawrence M, Alfonso Fernando, Schampaert Erick, Hassan Alita, McLain Richard, Pressler Milton L, Ibrahim Reda, Lespérance Jacques, Blue John, Heinonen Therese, Rodés-Cabau Josep
Montreal Heart Institute, 5000 Belanger St, Montreal, H1T 1C8, Canada.
Circulation. 2004 Nov 23;110(21):3372-7. doi: 10.1161/01.CIR.0000147777.12010.EF. Epub 2004 Nov 8.
Inhibition of the acyl coenzyme A:cholesterol acyltransferase (ACAT) enzyme may prevent excess accumulation of cholesteryl esters in macrophages. The ACAT inhibitor avasimibe was shown to reduce experimental atherosclerosis. This study was designed to investigate the effects of avasimibe on human coronary atherosclerosis.
This randomized, double-blind, placebo-controlled trial assessed the effects of avasimibe at dosages of 50, 250, and 750 mg QD on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients received background lipid-lowering therapy if necessary to reach a target baseline LDL level <125 mg/dL (3.2 mmol/L). IVUS and coronary angiography were performed at baseline and repeated after up to 24 months of treatment. Approximately equal percentages of patients across groups received concurrent statin therapy (87% to 89%). The mean total plaque volume at baseline was approximately 200 mm3, and the least squares mean change at end of treatment was 0.7 mm3 for placebo and 7.7, 4.1, and 4.8 mm3 for the avasimibe 50, 250, and 750 mg groups, respectively (adjusted P=0.17 [unadjusted P=0.057], 0.37, and 0.37, respectively). Percent atheroma volume increased by 0.4% with placebo and by 0.7%, 0.8%, and 1.0% in the respective avasimibe groups (P=NS). LDL cholesterol increased during the study by 1.7% with placebo but by 7.8%, 9.1%, and 10.9% in the respective avasimibe groups (P<0.05 in all groups).
Avasimibe did not favorably alter coronary atherosclerosis as assessed by IVUS. This ACAT inhibitor also caused a mild increase in LDL cholesterol.
抑制酰基辅酶A：胆固醇酰基转移酶（ACAT）可能会阻止胆固醇酯在巨噬细胞中的过度积累。ACAT抑制剂阿伐西丁已被证明可减轻实验性动脉粥样硬化。本研究旨在调查阿伐西丁对人类冠状动脉粥样硬化的影响。
这项随机、双盲、安慰剂对照试验评估了每日剂量为50、250和750毫克的阿伐西丁对冠状动脉粥样硬化进展的影响，通过血管内超声（IVUS）进行评估。所有患者在必要时接受背景降脂治疗，以使目标基线低密度脂蛋白水平<125毫克/分升（3.2毫摩尔/升）。在基线时进行IVUS和冠状动脉造影，并在治疗长达24个月后重复进行。各组中接受他汀类药物联合治疗的患者比例大致相同（87%至89%）。基线时的平均总斑块体积约为200立方毫米，治疗结束时安慰剂组的最小二乘平均变化为0.7立方毫米，阿伐西丁50、250和750毫克组分别为7.7、4.1和4.8立方毫米（校正P值=0.17[未校正P值=0.057]，分别为0.37和0.37）。安慰剂组的动脉粥样硬化体积百分比增加了0.4%，阿伐西丁各治疗组分别增加了0.7%、0.8%和1.0%（P=无显著性差异）。在研究期间，安慰剂组的低密度脂蛋白胆固醇增加了1.7%，而阿伐西丁各治疗组分别增加了7.8%、9.1%和10.9%（所有组P<0.05）。
通过IVUS评估，阿伐西丁并未对冠状动脉粥样硬化产生有利影响。这种ACAT抑制剂还导致低密度脂蛋白胆固醇轻度升高。
