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

Abstract

BackgroundThe 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.ObjectiveTo 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.MethodsRandomized 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.ResultsThe 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.ConclusionThe 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.

A comparison of the effects of monotherapy with rosuvastatin, atorvastatin or ezetimibe versus combination treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe on the integrity of vascular endothelial cells damaged by oxidized cholesterol

“…Garcia et al . (2016) [ 26 ] compared the effect of a high dose of simvastatin (80 mg/day) with a low dose of simvastatin (10 mg/day) in combination with ezetimibe (10 mg/day) on endothelial function in patients. Endothelial function was assessed by a flow-mediated vasodilator (FMV) method measured before and after eight weeks of treatment.…”

Vascular inflammation and low‐density lipoproteins: is cholesterol the link? A lesson from the clinical trials

“…Similar LDL‐C reductions from the baseline were obtained as well as similar improvement of FMD (Settergren et al , ). Similarly, obese women with LDL‐C ≥100 mg·dL −1 treated with simvastatin 80 mg or ezetimibe/simvastatin 10/10 mg for 8 weeks showed similar reductions of LDL‐C levels (−27% and −30%, respectively) and similar increases of FMD (+39% and +41%, respectively) (Garcia et al , ). These observations, suggesting that lipid‐lowering per se rather than pleiotropic properties of statins plays a key role in the improvement of endothelial function, were further supported by the results of a meta‐analysis including six trials with 213 participants which compared high‐dose statin versus low‐dose statin combined with ezetimibe (Ye et al , ).…”

Differential Therapeutic Effects of Crataegus aronia and Simvastatin on the Hepatocyte Ultrastructure in Hepatic Steatosis

“…2). The lipid lowering (Garcia et al, 2016), antioxidant (Eger et al, 2016) and antiinflammatory (Al-Ani, 2013) effects of simvastatin and the presence of polyphenolic antioxidants, flavonoids, oligomeric flavonoids (proanthocyanidins), and catechins (Kim et al, 2000) in the hawthorn plant could be the reason for the observed substantial treating effects of Crataegus aronia and simvastatin and a better architecture of liver cells.…”