Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial

被引：32

作者：

Jakulj, L. ^{[1
]}

Vissers, M. N. ^{[1
]}

Groen, A. K. ^{[3
]}

Hutten, B. A. ^{[2
]}

Lutjohann, D. ^{[4
]}

Veltri, E. P. ^{[5
]}

Kastelein, J. J. P. ^{[1
]}

机构：

[1] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Dept Epidemiol & Biostat, NL-1105 AZ Amsterdam, Netherlands

[3] Univ Groningen, Ctr Liver Digest & Metab Dis, NL-9700 AB Groningen, Netherlands

[4] Univ Bonn, Inst Clin Chem & Pharmacol, D-5300 Bonn, Germany

[5] Schering Plough Res Inst, Kenilworth, NJ USA

来源：

JOURNAL OF LIPID RESEARCH | 2010年 / 51卷 / 04期

关键词：

cholesterol synthesis; statins; familial hypercholesterolemia; DENSITY-LIPOPROTEIN RECEPTOR; SERUM PLANT STEROLS; FAMILIAL HYPERCHOLESTEROLEMIA; CORONARY-PATIENTS; PLASMA-CONCENTRATIONS; STATIN TREATMENT; SIMVASTATIN; CHOLESTANOL; METABOLISM; EZETIMIBE;

D O I：

10.1194/jlr.M001487

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Subjects with increased cholesterol absorption might benefit more from statin therapy combined with a cholesterol absorption inhibitor. We assessed whether baseline cholesterol absorption markers were associated with response to ezetimibe/simvastatin therapy, in terms of LDL-cholesterol (LDL-C) lowering and cholesterol absorption inhibition, in patients with familial hypercholesterolemia (FH). In a posthoc analysis of the two-year ENHANCE trial, we assessed baseline cholesterol-adjusted campesterol (campesterol/TC) and sitosterol/TC ratios in 591 FH patients. Associations with LDL-C changes and changes in cholesterol absorption markers were evaluated by multiple regression analysis. No association was observed between baseline markers of cholesterol absorption and the extent of LDL-C response to ezetimibe/simvastatin therapy (beta = 0.020, P = 0.587 for campesterol/TC and beta < 0.001, P = 0.992 for sitosterol/TC). Ezetimibe/simvastatin treatment reduced campesterol levels by 68% and sitosterol levels by 62%; reductions were most pronounced in subjects with the highest cholesterol absorption markers at baseline, the so-called high absorbers (P < 0.001). Baseline cholesterol absorption status does not determine LDL-C lowering response to ezetimibe/simvastatin therapy in FH, despite more pronounced cholesterol absorption inhibition in high absorbers. Hence, these data do not support the use of baseline absorption markers as a tool to determine optimal cholesterol lowering strategy in FH patients. However, due to the exploratory nature of any posthoc analysis, these results warrant further prospective evaluation in different populations.-Jakulj, L., M. N. Vissers, A. K. Groen, B. A. Hutten, D. Lutjohann, E. P. Veltri, and J. J. P. Kastelein. Baseline cholesterol absorption and the response to ezetimibe/simvastatin therapy: a post-hoc analysis of the ENHANCE trial. J. Lipid Res. 2010. 51: 755-762.

引用

页码：755 / 762

页数：8

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