AIM: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. METHODS: This post hoc analysis compared the effects of treatment with ezetimibe/simvastatin 10/20 mg vs. atorvastatin 10 and 20 mg/day and ezetimibe/simvastatin 10/40 mg/day vs. atorvastatin 40 mg/day on the cholesterol content of lipoprotein subclasses in the modified intent-to-treat (mITT) population (n = 1013) and in subgroups of patients with triglyceride (TG) levels <200 mg/dl (n = 600) and >or=200 mg/dl (2.6 mmol/l) (n = 413). RESULTS:Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL(1)-C, LDL(2)-C and LDL(3)-C; real LDL-C (LDL-C(r)); intermediate-density lipoprotein cholesterol (IDL-C), IDL(1)-C, IDL(2)-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL(3)-C; and remnant-like lipoprotein cholesterol (RLP-C) from baseline more than atorvastatin at all dose comparisons (p < 0.01) in the mITT population. Significant improvements were also observed in high-density lipoprotein cholesterol (HDL-C) subclass HDL(3)-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL(1 + 2)-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL(4)-C and LDL-C subclass patterns (A, B and I) were comparable for both treatments. Generally, similar results were observed for patients with TG levels <200 and >or=200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL(2)-C, slightly smaller decreases in all IDL subclasses and greater decreases in all VLDL-C subclasses than those with lower TG levels. Frequency of pattern B was also reduced more in patients with higher TGs for both treatments. CONCLUSIONS:Ezetimibe/simvastatin reduced the cholesterol content of most lipoprotein subclasses from baseline with generally similar efficacy in patients with low and high TGs. Despite the different mechanism of action of ezetimibe, the response to ezetimibe/simvastatin and atorvastatin treatment related to these lipoprotein subclasses was generally consistent with the overall effects of these therapies on the major lipid/lipoprotein classes. The clinical significance of these results awaits further study.
RCT Entities:
AIM: To evaluate the effects of the usual starting and next higher doses of ezetimibe/simvastatin and atorvastatin on the cholesterol content of lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. METHODS: This post hoc analysis compared the effects of treatment with ezetimibe/simvastatin 10/20 mg vs. atorvastatin 10 and 20 mg/day and ezetimibe/simvastatin 10/40 mg/day vs. atorvastatin 40 mg/day on the cholesterol content of lipoprotein subclasses in the modified intent-to-treat (mITT) population (n = 1013) and in subgroups of patients with triglyceride (TG) levels <200 mg/dl (n = 600) and >or=200 mg/dl (2.6 mmol/l) (n = 413). RESULTS:Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL(1)-C, LDL(2)-C and LDL(3)-C; real LDL-C (LDL-C(r)); intermediate-density lipoprotein cholesterol (IDL-C), IDL(1)-C, IDL(2)-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL(3)-C; and remnant-like lipoprotein cholesterol (RLP-C) from baseline more than atorvastatin at all dose comparisons (p < 0.01) in the mITT population. Significant improvements were also observed in high-density lipoprotein cholesterol (HDL-C) subclass HDL(3)-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL(1 + 2)-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL(4)-C and LDL-C subclass patterns (A, B and I) were comparable for both treatments. Generally, similar results were observed for patients with TG levels <200 and >or=200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL(2)-C, slightly smaller decreases in all IDL subclasses and greater decreases in all VLDL-C subclasses than those with lower TG levels. Frequency of pattern B was also reduced more in patients with higher TGs for both treatments. CONCLUSIONS:Ezetimibe/simvastatin reduced the cholesterol content of most lipoprotein subclasses from baseline with generally similar efficacy in patients with low and high TGs. Despite the different mechanism of action of ezetimibe, the response to ezetimibe/simvastatin and atorvastatin treatment related to these lipoprotein subclasses was generally consistent with the overall effects of these therapies on the major lipid/lipoprotein classes. The clinical significance of these results awaits further study.
Authors: Wu Yin; Ester Carballo-Jane; David G McLaren; Vivienne H Mendoza; Karen Gagen; Neil S Geoghagen; Lesley Ann McNamara; Judith N Gorski; George J Eiermann; Aleksandr Petrov; Michael Wolff; Xinchun Tong; Larissa C Wilsie; Taro E Akiyama; Jing Chen; Anil Thankappan; Jiyan Xue; Xiaoli Ping; Genevieve Andrews; L Alexandra Wickham; Cesaire L Gai; Tu Trinh; Alison A Kulick; Marcie J Donnelly; Gregory O Voronin; Ray Rosa; Anne-Marie Cumiskey; Kavitha Bekkari; Lyndon J Mitnaul; Oscar Puig; Fabian Chen; Richard Raubertas; Peggy H Wong; Barbara C Hansen; Ken S Koblan; Thomas P Roddy; Brian K Hubbard; Alison M Strack Journal: J Lipid Res Date: 2011-10-23 Impact factor: 5.922
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Authors: Ngoc-Anh Le; Ran Jin; Joanne E Tomassini; Andrew M Tershakovec; David R Neff; Peter W F Wilson Journal: J Am Heart Assoc Date: 2013-08-07 Impact factor: 5.501