Abstract 1176: A Single Dose of Clopidogrel Causes Dose-Dependent Improvement of Endothelial Dysfunction in Patients with Stable Coronary Artery Disease

Background: Clinical studies have shown beneficial effects for the ADP-P2Y12 receptor antagonist clopidogrel in patients with coronary artery disease (CAD). Recent in-vitro studies identified stimulating effects of clopidogrel on endothelial cells, pointing towards mechanisms of action beyond the inhibition of platelet aggregation. However, it is not known, whether clopidogrel improves endothelial function in-vivo. We therefore hypothesized that in-vivo use of clopidogrel improves endothelial dysfunction. Methods: In a double-blind, randomized study, 58 patients with CAD received one dose of clopidogrel 300mg (C300) or 600mg (C600), respectively. Endothelial function was assessed by measurement of flow-mediated dilation (FMD) of the brachial artery before and 2, 4 and 22 hours after the dose application, respectively. Inhibition of the platelet ADP P2Y12 receptor by clopidogrel was monitored by the ex-vivo analysis of ADP effects on prostaglandin-induced platelet VASP phosphorylation. Results: C600 significantly improved FMD at 2, 4 and 22 hours, while C300 significantly improved FMD at 4 and 22 hours (Figure 1). Clopidogrel dose- and time-dependently inhibited the platelet ADP-P2Y12 receptor without correlation with its stimulatory effects on FMD. Conclusions: Our study demonstrates for the first time, that clopidogrel dose-dependently improves endothelial dysfunction. These results may indicate a new and potentially important aspect of the effect of clopidogrel treatment in patients with CAD. Further studies to investigate the long-term effect of clopidogrel treatment on endothelial function are warranted.