Clopidogrel improves microvascular endothelial function in subjects with stable coronary artery disease

Abstract

BACKGROUND: Clopidogrel therapy has recently been shown to reduce cardiovascular events in patients with stable vascular disease. This benefit may be due to effects not exclusively related to platelet aggregation. The aim of this study was to evaluate the effect of clopidogrel therapy on microvascular endothelial function in subjects with stable coronary artery disease (CAD). METHODS AND RESULTS: Forty subjects with stable CAD were randomised to clopidogrel therapy (75mg/day) or control. Blood and endothelial function testing occurred at baseline, one week and three months following randomisation. Microvascular endothelial function was assessed via reactive hyperaemic index (RHI). Platelet function was assessed by adenosine diphosphate (ADP)-induced whole blood aggregation and the VerifyNow™ system. Plasma markers of endothelial function (asymmetric dimethylarginine, ADMA) and oxidative stress (myeloperoxidase, MPO) were also tested. The primary endpoint was endothelial function assessment (RHI) at three months. At one week RHI increased by 20±10% in the clopidogrel group; this effect was maintained at three months (21±9% increase from baseline; P<0.01). A significant decrease in ADP-induced platelet aggregation and P2Y12 reaction units was observed in the clopidogrel therapy group (P<0.01). There was no correlation between endothelial function and platelet function testing in the clopidogrel therapy group. CONCLUSION: Clopidogrel therapy is associated with improved microvascular endothelial function in patients with stable CAD. This effect is independent of its effects on ADP-induced platelet reactivity.