Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia

J. E. Tomassini, T. Mazzone, Ronald B Goldberg, J. R. Guyton, R. S. Weinstock, A. Polis, E. Jensen, Andrew M. Tershakovec

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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 ≥200 mg/dl (2.6 mmol/l) (n = 413). Results: Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL1-C, LDL2-C and LDL3-C; real LDL-C (LDL-Cr; intermediate-density lipoprotein cholesterol (IDL-C), IDL1-C, IDL2-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL3-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 HDL3-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL1+2-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL4-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 ≥200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL2-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.

Original languageEnglish
Pages (from-to)855-864
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume11
Issue number9
DOIs
StatePublished - Sep 3 2009

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Simvastatin
Hypercholesterolemia
Type 2 Diabetes Mellitus
Lipoproteins
Triglycerides
LDL Lipoproteins
LDL Cholesterol
VLDL Cholesterol
Therapeutics
Ezetimibe
Atorvastatin Calcium
HDL Cholesterol
Population
Cholesterol
Lipids
lipoprotein cholesterol

Keywords

  • Atorvastatin
  • Ezetimibe/simvastatin
  • Hypertriglyceridaemia
  • Lipoprotein subclasses
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. / Tomassini, J. E.; Mazzone, T.; Goldberg, Ronald B; Guyton, J. R.; Weinstock, R. S.; Polis, A.; Jensen, E.; Tershakovec, Andrew M.

In: Diabetes, Obesity and Metabolism, Vol. 11, No. 9, 03.09.2009, p. 855-864.

Research output: Contribution to journalArticle

Tomassini, J. E. ; Mazzone, T. ; Goldberg, Ronald B ; Guyton, J. R. ; Weinstock, R. S. ; Polis, A. ; Jensen, E. ; Tershakovec, Andrew M. / Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia. In: Diabetes, Obesity and Metabolism. 2009 ; Vol. 11, No. 9. pp. 855-864.
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abstract = "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 ≥200 mg/dl (2.6 mmol/l) (n = 413). Results: Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL1-C, LDL2-C and LDL3-C; real LDL-C (LDL-Cr; intermediate-density lipoprotein cholesterol (IDL-C), IDL1-C, IDL2-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL3-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 HDL3-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL1+2-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL4-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 ≥200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL2-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.",
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T1 - Effect of ezetimibe/simvastatin compared with atorvastatin on lipoprotein subclasses in patients with type 2 diabetes and hypercholesterolaemia

AU - Tomassini, J. E.

AU - Mazzone, T.

AU - Goldberg, Ronald B

AU - Guyton, J. R.

AU - Weinstock, R. S.

AU - Polis, A.

AU - Jensen, E.

AU - Tershakovec, Andrew M.

PY - 2009/9/3

Y1 - 2009/9/3

N2 - 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 ≥200 mg/dl (2.6 mmol/l) (n = 413). Results: Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL1-C, LDL2-C and LDL3-C; real LDL-C (LDL-Cr; intermediate-density lipoprotein cholesterol (IDL-C), IDL1-C, IDL2-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL3-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 HDL3-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL1+2-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL4-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 ≥200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL2-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.

AB - 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 ≥200 mg/dl (2.6 mmol/l) (n = 413). Results: Ezetimibe/simvastatin significantly reduced low-density lipoprotein cholesterol (LDL-C) subclasses LDL1-C, LDL2-C and LDL3-C; real LDL-C (LDL-Cr; intermediate-density lipoprotein cholesterol (IDL-C), IDL1-C, IDL2-C; very low-density lipoprotein cholesterol (VLDL-C), VLDL3-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 HDL3-C at the ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg and highest dose comparisons (p < 0.001) and in VLDL1+2-C at the lowest and highest dose comparisons (p < 0.001). Changes in LDL4-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 ≥200 mg/dl (2.3 mmol). For both treatments, notable differences between TG subgroups were that patients with elevated TGs had smaller reductions in LDL2-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.

KW - Atorvastatin

KW - Ezetimibe/simvastatin

KW - Hypertriglyceridaemia

KW - Lipoprotein subclasses

KW - Type 2 diabetes

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