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

• Main Authors: Maristela Magnavita Oliveira Garcia, 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
• Format: Article
• Language: English
• Published: Sociedade Brasileira de Cardiologia (SBC) 2016-04-01
• Series: Arquivos Brasileiros de Cardiologia
• Subjects: Endotélio / fisiologia; Colesterol; Inibidores de Hidroximetil glutaril-CoA Redutases / uso terapêutico; Ezetimiba; Anticolesterolemiantes.
• Online Access: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0066-782X2016000400279&lng=en&tlng=en

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.