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  2. Keyword: Ezetimibe
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Original Article

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe

Maristela Magnavita Oliveira Garcia et al. Carolina Garcez Varela Patricia Fontes Silva Paulo Roberto Passos Lima … Paulo Meira Góes Marilia Galeffi Rodrigues Maria de Lourdes Lima Souza e Silva Ana Marice Teixeira Ladeia Armênio Costa Guimarães Luis Claudio Lemos Correia

Abstract

Background:

The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect.

Objective:

To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered.

Methods:

Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment.

Results:

The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function.

Conclusion:

The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

  • Anticholesterolemic Agents
  • Cholesterol
  • Endothelium / physiology
  • Ezetimibe
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
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Creative Commons Attribution (CC BY) Creative Commons license
01/04/2016 DOI: 10.5935/abc.20160048 Views 1
ABC
Viewpoint

Ezetimibe: Clinical and Scientific Meaning of the IMPROVE-IT Study

Luis C. L. Correia

Ezetimibe: Clinical and scientific meaning of the IMPROVE-IT study

After years of anxious wait, in June of the current year, the results of the clinical trial IMPROVE-IT were published in the New England Journal of Medicine. This was the first study to properly evaluate the clinical impact of adding ezetimibe to statin therapy. Until then, we had known that the combination of ezetimibe with statin enhanced the antihyperlipidemic effect of statins (surrogate endpoint). However, a positive surrogate marker does not necessarily have a guaranteed clinical impact on the therapy. Therefore, the IMPROVE-IT would fill a gap in the literature concerning the effect of ezetimibe on clinical outcomes.

The publication of the ENHANCE study in 2008 created uncertainty about the efficacy of the therapy with ezetimibe. In this randomized, clinical trial including patients with familial hypercholesterolemia, the therapy with ezetimibe added to 80 mg of simvastatin led to greater reductions in LDL cholesterol levels as compared with simvastatin alone. However, the effect was not accompanied by a greater reduction in atherosclerosis, measured by the carotid intima-media thickness (surrogate endpoint). At this point, it became evident that the industry was precipitate in promoting the use of a drug before its effects were demonstrated by clinical outcomes.

[…]

  • Cholesterol
  • Drug Combination
  • Ezetimibe
  • Hydroxymethylglutaryl CoA- Redutases
  • Hypolipidemic Agents
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Creative Commons Attribution (CC BY) Creative Commons license
01/03/2016 DOI: 10.5935/abc.20160033 Views 2
ABC
Artigo de Pesquisa

Ezetimibe: pharmacokinetics and therapeutics

Renata G. Araújo et al. Antonio Casella Filho Antonio Carlos P. Chagas

Ezetimibe is an inhibitor of cholesterol absorption that is liver glucuronized after its rapid absorption, and is mobilized to the enterocytes, where together with its metabolites it exerts hypolipidemic effects, avoiding the absorption of cholesterol, through the reduction of specific cholesterol-transporter enzymes in the gut. This drug can be given once daily due to its prolonged plasma half-life, and is usually very well-tolerated. Elimination of ezetimibe and its metabolites is mainly via fecal excretion. In general, the use of ezetimibe alone promotes modest effects on plasma LDL-c, however, when combined with statins, a remarkable change in the lipid profile can be observed.

  • Ezetimibe
  • Metabolism
  • statin
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Creative Commons Attribution (CC BY) Creative Commons license
02/01/2006 DOI: 10.1590/S0066-782X2005002400006 Views 1

How to cite this article

EndNote RIS

Electronic Document Format (Vancouver)

Garcia MMO, Varela CG, Silva PF, Lima PRP, Góes PM, Rodrigues MG, Silva MLLS, et al. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe. Arquivos Brasileiros de Cardiologia 2016;106(4):279-88.

Electronic Document Format (ABNT)

Garcia, Maristela Magnavita Oliveira; Varela, Carolina Garcez; Silva, Patricia Fontes; Lima, Paulo Roberto Passos; Góes, Paulo Meira; Rodrigues, Marilia Galeffi; Silva, Maria de Lourdes Lima Souza e; Ladeia, Ana Marice Teixeira; Guimarães, Armênio Costa; Correia, Luis Claudio Lemos. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe. Arquivos Brasileiros de Cardiologia, v. 106, n. 4, p. 279-288, Mar. 2016.

Electronic Document Format (APA)

Garcia, M. M. O., Varela, C. G., Silva, P. F., Lima, P. R. P., Góes, P. M., Rodrigues, M. G., Silva, M. L. L. S. , Ladeia, A. M. T., Guimarães, A. C., & Correia, L. C. L. (2016). Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe. Arquivos Brasileiros de Cardiologia, 106(4), 279-288.

Electronic Document Format (ISO)

Garcia, Maristela Magnavita Oliveira and Varela, Carolina Garcez and Silva, Patricia Fontes and Lima, Paulo Roberto Passos and Góes, Paulo Meira and Rodrigues, Marilia Galeffi and Silva, Maria de Lourdes Lima Souza e and Ladeia, Ana Marice Teixeira and Guimarães, Armênio Costa and Correia, Luis Claudio Lemos. Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe. Arquivos Brasileiros de Cardiologia [online]. 2016, vol. 106, n. 4, [cited 2026-10-14], pp. 279-288. Available from: <https://journals.cardiol.br/en/article/endothelial-effect-of-statin-therapy-at-a-high-dose-versus-low-dose-associated-with-ezetimibe/>. ISSN 0066-782X

EndNote RIS

Electronic Document Format (Vancouver)

Correia LCL. Ezetimibe: Clinical and Scientific Meaning of the IMPROVE-IT Study. Arquivos Brasileiros de Cardiologia 2016;106(3):247-9.

Electronic Document Format (ABNT)

Correia, Luis C. L.. Ezetimibe: Clinical and Scientific Meaning of the IMPROVE-IT Study. Arquivos Brasileiros de Cardiologia, v. 106, n. 3, p. 247-249, Feb. 2016.

Electronic Document Format (APA)

Correia, L. C. L. (2016). Ezetimibe: Clinical and Scientific Meaning of the IMPROVE-IT Study. Arquivos Brasileiros de Cardiologia, 106(3), 247-249.

Electronic Document Format (ISO)

Correia, Luis C. L.. Ezetimibe: Clinical and Scientific Meaning of the IMPROVE-IT Study. Arquivos Brasileiros de Cardiologia [online]. 2016, vol. 106, n. 3, [cited 2026-10-14], pp. 247-249. Available from: <https://journals.cardiol.br/en/article/ezetimibe-clinical-and-scientific-meaning-of-the-improve-it-study/>. ISSN 0066-782X

EndNote RIS

Electronic Document Format (Vancouver)

Araújo RG, Casella Filho A, Chagas ACP. Ezetimibe: pharmacokinetics and therapeutics. Arquivos Brasileiros de Cardiologia 2006;85(suppl 5):20-4.

Electronic Document Format (ABNT)

Araújo, Renata G.; Casella Filho, Antonio; Chagas, Antonio Carlos P.. Ezetimibe: pharmacokinetics and therapeutics. Arquivos Brasileiros de Cardiologia, v. 85, n. suppl 5, p. 20-24, Jan. 2006.

Electronic Document Format (APA)

Araújo, R. G., Casella Filho, A., & Chagas, A. C. P. (2006). Ezetimibe: pharmacokinetics and therapeutics. Arquivos Brasileiros de Cardiologia, 85(suppl 5), 20-24.

Electronic Document Format (ISO)

Araújo, Renata G. and Casella Filho, Antonio and Chagas, Antonio Carlos P.. Ezetimibe: pharmacokinetics and therapeutics. Arquivos Brasileiros de Cardiologia [online]. 2006, vol. 85, n. suppl 5, [cited 2026-10-14], pp. 20-24. Available from: <https://journals.cardiol.br/en/article/ezetimibe-pharmacokinetics-and-therapeutics/>. ISSN 0066-782X

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