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  • Title: Changes in LDL particle concentrations after treatment with the cholesteryl ester transfer protein inhibitor anacetrapib alone or in combination with atorvastatin.
    Author: Krauss RM, Pinto CA, Liu Y, Johnson-Levonas AO, Dansky HM.
    Journal: J Clin Lipidol; 2015; 9(1):93-102. PubMed ID: 25670366.
    Abstract:
    OBJECTIVES: Our aim was to assess the effects of the cholesteryl ester transfer protein (CETP) inhibitor anacetrapib and atorvastatin, both as monotherapy and in combination, on particle concentrations of low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), and intermediate-density lipoproteins in dyslipidemic patients. BACKGROUND: Although increases in high-density lipoproteins with CETP inhibition are well-documented, effects on atherogenic lipoprotein particle subclasses in dyslipidemic patients have not been extensively characterized. METHODS: Ion mobility was performed on stored plasma samples collected from patients before and after treatment with anacetrapib alone (150 and 300 mg/d) or in combination with atorvastatin (20 mg/d) in a previously conducted 8-week phase IIb study. RESULTS: Anacetrapib produced significant placebo-adjusted reductions of total LDL particles and all subfractions except for increases in very small LDL 4a and 4b. Atorvastatin reduced all LDL subfractions except LDL 4b. Results were generally additive for anacetrapib + atorvastatin. For patients treated with anacetrapib, the placebo-adjusted reduction in LDL 3a was attenuated and there was an increase in LDL 3b and 4a for those with low vs high triglyceride (TG) levels. For the atorvastatin alone vs placebo treatment comparison, there were small reductions in LDL 3a, 3b, and 4a for those with low vs high TG levels. CONCLUSIONS: Anacetrapib and atorvastatin produced similar reductions from baseline in total LDL particles, but did not have comparable effects on all LDL particle subfractions, and neither drug reduced the smallest LDL 4b particles. The clinical significance of these changes and the differential effects on very small LDL 4a in patients with higher vs lower TG remain to be determined (clinicaltrials.gov, NCT00325455).
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