Publication: Effects of ezetimibe added to statin therapy on markers of cholesterol absorption and synthesis and LDL-C lowering in hyperlipidemic patients
Issued Date
2012-12-01
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ISSN
18791484
00219150
00219150
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2-s2.0-84869502184
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Mahidol University
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SCOPUS
Bibliographic Citation
Atherosclerosis. Vol.225, No.2 (2012), 388-396
Suggested Citation
Nuntakorn Thongtang, Jianxin Lin, Ernst J. Schaefer, Robert S. Lowe, Joanne E. Tomassini, Arvind K. Shah, Andrew M. Tershakovec Effects of ezetimibe added to statin therapy on markers of cholesterol absorption and synthesis and LDL-C lowering in hyperlipidemic patients. Atherosclerosis. Vol.225, No.2 (2012), 388-396. doi:10.1016/j.atherosclerosis.2012.09.001 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/14469
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Title
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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Abstract
Objective: 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 on-going 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. Methods: 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 p redicted LDL-C-lowering effects of each ongoing statin type and dose (reductions of ∼20-30%, ∼31-45%, or ∼46-55%, respectively). Results: 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. Conclusion: 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. © 2012 Published by Elsevier Ireland Ltd..