Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

Abstract

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3<T1 and T4 for total cholesterol, LDL-C, and triglycerides; P<0.002 for all), as well as for endothelial function (T2>T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1<T3 and T4, P=0.034) and clopidogrel (adenosine, T3 and T4<T1 and T2, P<0.0001) therapy. Simvastatin/ezetimibe diphosphate did not change platelet aggregation, the amount of circulating endothelial and platelet microparticles, or endothelial progenitor cells. Cardiovascular protection following therapy with simvastatin/ezetimibe seems restricted to lipid changes and improvement of endothelial function not affecting the release of microparticles, mobilization of endothelial progenitor cells or decreased platelet aggregation.

Effect of endothelin‐1 and endothelin receptor blockade on the release of microparticles

“… showed that statin treatment leads to a reduction in circulatory levels of EMP, the study by Camargo et al . failed to show any effect of simvastatin and ezetimibe treatment on EMP levels. Esposito et al .…”

“…However, results of clinical trials evidenced discrepancies. Whereas Huang et al [27] and Suades et al [28] showed that statin treatment leads to a reduction in circulatory levels of EMP, the study by Camargo et al [29] failed to show any effect of simvastatin and ezetimibe treatment on EMP levels. Esposito et al [30] provided evidence that pioglitazone treatment led to a reduction in CD31+ EMP and to an increase in circulating endothelial progenitor cells.…”

Platelet Microvesicles (Microparticles) in Cardiac Surgery

“…45 However, one study found that anti-platelet drugs did not have an effect on populations of circulating PMV. 46 These conflicting results warrant further investigation into the effect of antiplatelet agents on PMV populations.…”

“…Statins have no effect on PMV numbers. 44,46 Intravenous fluids A variety of crystalloid and colloid fluids, and blood components, are administered during surgery and CPB. Hemodilution reduces blood viscosity, allowing potentially faster blood flow and increased shear stresses within the cardiovascular system.…”

Applicability of extracellular vesicles in clinical studies

“…Additionally, we included 25 publications that fulfilled inclusion criteria but were found otherwise. Final analysis was performed on 65 publications (Fig. ).…”