Effects of ezetimibe added to statin therapy on markers of cholesterol absorption and synthesis and LDL-C lowering in hyperlipidemic patients.
Effects of ezetimibe added to statin therapy on markers of cholesterol absorption and synthesis and LDL-C lowering in hyperlipidemic patients.
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DOI：
10.1016/j.atherosclerosis.2012.09.001
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发表时间：
2012-12
期刊：
影响因子：
5.3
通讯作者：
Tershakovec, Andrew M.
中科院分区：
文献类型：
--
作者：
Thongtang, Nuntakorn;Lin, Jianxin;Schaefer, Ernst J.;Lowe, Robert S.;Tomassini, Joanne E.;Shah, Arvind K.;Tershakovec, Andrew M.
他汀类药物抑制胆固醇合成，但可以上调胆固醇吸收，剂量越高，效果越大。依折麦布抑制胆固醇吸收，但也上调合成。我们检测了依折麦布加用正在进行的他汀类药物治疗是否最有效降低接受高效他汀类药物治疗的受试者的LDL-胆固醇（LDL-C），以及这些效应是否与胆固醇吸收（β-谷甾醇）和合成（脂甾醇）标志物的改变相关。接受他汀类药物治疗的高胆固醇血症受试者（n=874）接受依折麦布10 mg/天。在基线和治疗时测量血脂、脂甾醇和β-谷甾醇。受试者被分为低（n=133）、中（n=582）和高（n=159）他汀类药物效力组，根据每种正在进行的他汀类药物类型和剂量的预测LDL-C降低效应进行定义（分别降低约20- 30%、约31- 45%或约46- 55%）。与中/低效价组相比，高效价组的基线脂甾醇值显著较低（1.93 vs. 2.58 vs. 3.17 μmol/l; p <0.001），基线β-谷甾醇值显著较高（6.21 vs. 4.58 vs. 4.51 μmol/l，p <0.001）。当评价未校正数据时，高效价组中依折麦布治疗产生的LDL-C较基线的降幅显著大于中/低效价组（−29.1% vs. −25.0% vs. −22.7%; p <0.001）。这些效应和组间差异与β-谷甾醇减少量较大和豆甾醇增加量较小显著相关（p <0.05）。然而，在控制安慰剂效应后，组间LDL-C降低差异不再显著，主要是由于高效组中安慰剂的LDL-C适度降低。接受高效他汀类药物治疗的患者基线时胆固醇合成标志物水平最低，胆固醇吸收标志物水平最高，添加依折麦布后，吸收标志物降低幅度最大，合成标志物增加幅度最小。因此，如果需要额外降低LDL-C，此类患者可能是依折麦布治疗的良好候选者。
Statins inhibit cholesterol synthesis but can upregulate cholesterol absorption, with higher doses producing larger effects. Ezetimibe inhibits cholesterol absorption but also upregulates synthesis. We tested whether ezetimibe added to ongoing statin therapy would be most effective in lowering LDL-cholesterol (LDL-C) in subjects on high-potency statins and whether these effects would be related to alterations in cholesterol absorption (β-sitosterol) and synthesis (lathosterol) markers. Hypercholesterolemic subjects (n=874) on statins received ezetimibe 10 mg/day. Plasma lipids, lathosterol, and β-sitosterol were measured at baseline and on treatment. Subjects were divided into low- (n=133), medium- (n=582), and high- (n=159) statin potency groups defined by predicted LDL-C–lowering effects of each ongoing statin type and dose (reductions of ~20-30%, ~31-45%, or ~46-55%, respectively). The high-potency group had significantly lower baseline lathosterol (1.93 vs. 2.58 vs. 3.17 μmol/l; p <0.001) and higher baseline β-sitosterol values (6.21 vs. 4.58 vs. 4.51 μmol/l, p <0.001) than medium-/low-potency groups. Ezetimibe treatment in the high-potency group produced significantly greater reductions from baseline in LDL-C than medium-/low-potency groups (−29.1% vs. −25.0% vs. −22.7%; p <0.001) when evaluating unadjusted data. These effects and group differences were significantly (p <0.05) related to greater β-sitosterol reductions and smaller lathosterol increases. However, LDL-C reduction differences between groups were no longer significant after controlling for placebo effects, due mainly to modest LDL-C lowering by placebo in the high-potency group. Patients on high-potency statins have the lowest levels of cholesterol synthesis markers and the highest levels of cholesterol absorption markers at baseline, and the greatest reduction in absorption markers and the smallest increases in synthesis markers with ezetimibe addition. Therefore, such patients may be good candidates for ezetimibe therapy if additional LDL-C lowering is needed.
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影响因子：
158.5
作者：
REIHNER, E;RUDLING, M;ANGELIN, B
通讯作者：
ANGELIN, B
影响因子：
37.8
作者：
Ballantyne, CM;Houri, J;Veltri, EP
通讯作者：
Veltri, EP
影响因子：
5.3
作者：
Gouni-Berthold, Ioanna;Berthold, Heiner K.;Krone, Wilhelm
通讯作者：
Krone, Wilhelm
影响因子：
6.5
作者：
Lamon-Fava, Stefania;Diffenderfer, Margaret R.;Schaefer, Ernst J.
通讯作者：
Schaefer, Ernst J.
影响因子：
5.3
作者：
Ooi, Esther M. M.;Barrett, P. Hugh R.;Watts, Gerald F.
通讯作者：
Watts, Gerald F.