Abstract 11757: Clopidogrel Improves Microvascular Endothelial Function in Patients with Stable Coronary Artery Disease
Background: Recent data has shown clopidogrel therapy may be beneficial in reducing cardiovascular adverse events in patients with established atherothrombotic disease. Several studies have suggested that the benefit of clopidogrel may be, in part, due to effects not exclusively related to platelet aggregation. The primary 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: Forty patients with stable CAD on long-term aspirin therapy were randomized to clopidogrel therapy (75mg/daily) or control. Platelet function and microvascular endothelial function were assessed at baseline, one week and three months following randomization. Platelet function testing involved whole blood impedance aggregation (ADP 5μ mol/L and 20μ mol/L). Microvascular endothelial function was assessed using peripheral arterial tonometry device (Endo-PAT). Plasma levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and the heme enzyme myeloperoxidase (MPO) were also quantified.
Results: The mean age of the cohort was 63.8±1.5 (SE). The baseline mean RHI for the cohort was 1.78±0.1 RHI. 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). There was a significant decrease in ADP-induced platelet aggregation in patients on clopidogrel at both concentrations (p<0.01). There was no correlation between baseline RHI and platelet aggregation (p=0.99, r2=0.0) or between change in endothelial function and change in ADP-induced platelet aggregation in the clopidogrel arm (p=0.51, r2=0.03). Clopidogrel therapy did not affect ADMA or MPO levels at either timepoint.
Conclusion: Long-term clopidogrel improves microvascular endothelial function in patients with stable CAD independent of changes in ADMA or MPO levels. These data suggest that the pleiotrophic effect of clopidogrel on small vessel function maybe mediated by an endothelium-derived relaxing factor (EDRF) other than nitric oxide.
- © 2012 by American Heart Association, Inc.