依泽替米贝对低密度脂蛋白亚型分布的影响：一项在接受常规低密度脂蛋白去除法和他汀类药物治疗的患者中进行的安慰剂对照双盲试验结果

Effect of ezetimibe on low-density lipoprotein subtype distribution: results of a placebo-controlled, double-blind trial in patients treated by regular low-density lipoprotein apheresis and statins.

作者信息

Geiss H Christian, Otto Carsten, Parhofer Klaus G

机构信息

Medical Department I, University Mainz, 55131 Mainz, Germany.

出版信息

Metabolism. 2006 May;55(5):599-604. doi: 10.1016/j.metabol.2005.11.015.

DOI:10.1016/j.metabol.2005.11.015

PMID:16631435

Abstract

Ezetimibe, a cholesterol absorption inhibitor, can be combined with statins to lower low-density lipoprotein (LDL) cholesterol. We have previously shown that ezetimibe can decrease LDL cholesterol by 16% even in patients treated by regular LDL apheresis and statins (Atherosclerosis. 2005;180:107-112). However, it is unclear whether ezetimibe decreases all LDL subfractions equally in patients with hypercholesterolemia. We therefore evaluated the effect of ezetimibe (5 weeks, 10 mg/d) on LDL subtype distribution in a placebo-controlled, double-blind randomized crossover study in 20 patients (age, 56+/-9 years; body mass index, 27.5+/-4 kg/m2) with severe hyperlipoproteinemia and coronary heart disease who are treated by statins and regular LDL apheresis. Both treatment periods (placebo and ezetimibe) were separated by a 5-week washout period. Low-density lipoprotein subtype distribution was determined at the end of each treatment period before apheresis by density gradient ultracentrifugation (LDL1, 1.020-1.024; LDL2, 1.025-1.029; LDL3, 1.030-1.034; LDL4, 1.035-1.040; LDL5, 1.041-1.047; LDL6, 1.048-1.057; LDL7, 1.058-1.066 g/mL). Overall, the LDL subtype distribution did not change significantly (large-buoyant LDL [LDL1+LDL2], 17.2%+/-6.4% vs 16.3%+/-7.1%; intermediate LDL [LDL3+LDL4], 49.3%+/-4.5% vs 48.2%+/-5.2%; small-dense LDL [LDL5+LDL6+LDL7], 33.5%+/-8.0% vs 35.5%+/-10% during placebo and ezetimibe treatments, respectively). With respect to the individual LDL subfractions, cholesterol was significantly (P<.05, Wilcoxon test) reduced by ezetimibe in LDL1 to LDL5 with a somewhat more pronounced reduction in larger LDL (mean+/-SD, -20%+/-28%, -17%+/-32%, -14%+/-25%, -13%+/-27%, -11%+/-21%, -7%+/-21%, -4%+/-19%; median, -28%, -12%, -18%, -16%, -4%, -4%, -2% for LDL subfractions 1-7, respectively). We therefore conclude that ezetimibe decreases cholesterol in nearly all LDL subfractions. Although this was established in patients concomitantly treated with statins and apheresis, this may also hold true in other clinically relevant situations.

摘要

依折麦布是一种胆固醇吸收抑制剂，可与他汀类药物联合使用以降低低密度脂蛋白（LDL）胆固醇。我们之前已经表明，即使对于接受常规LDL单采和他汀类药物治疗的患者，依折麦布也能使LDL胆固醇降低16%（《动脉粥样硬化》。2005年；180:107 - 112）。然而，尚不清楚依折麦布是否能使高胆固醇血症患者的所有LDL亚组分均等地降低。因此，我们在一项安慰剂对照、双盲随机交叉研究中，评估了依折麦布（5周，10毫克/天）对20例（年龄，56±9岁；体重指数，27.5±4千克/平方米）患有严重高脂蛋白血症和冠心病且正在接受他汀类药物和常规LDL单采治疗的患者LDL亚型分布的影响。两个治疗期（安慰剂和依折麦布）之间间隔5周的洗脱期。在每次治疗期结束且在进行单采之前，通过密度梯度超速离心法（LDL1，1.020 - 1.024；LDL2，1.025 - 1.029；LDL3，1.030 - 1.034；LDL4，1.035 - 1.040；LDL5，1.041 - 1.047；LDL6，1.048 - 1.057；LDL7，1.058 - 1.066克/毫升）确定LDL亚型分布。总体而言，LDL亚型分布没有显著变化（大颗粒LDL[LDL1 + LDL2]，分别为17.2%±6.4%和16.3%±7.1%；中间LDL[LDL3 + LDL4]，分别为49.3%±4.5%和48.2%±5.2%；小而密LDL[LDL5 + LDL6 + LDL7]，在安慰剂和依折麦布治疗期间分别为33.5%±8.0%和%35.5±10%）。就各个LDL亚组分而言，依折麦布使LDL1至LDL5中的胆固醇显著降低（P<0.05，Wilcoxon检验），在较大的LDL中降低更为明显（均值±标准差，分别为-20%±28%，-17%±32%，-14%±25%，-13%±27%，-11%±21%，-7%±21%，-4%±19%；LDL亚组分1 - 7的中位数分别为-28%，-12%，-18%，-16%，-4%，-4%，-2%）。因此，我们得出结论，依折麦布能降低几乎所有LDL亚组分中的胆固醇。尽管这是在同时接受他汀类药物和单采治疗的患者中确定的，但在其他临床相关情况下可能也成立。