Abstract 15265: Clopidogrel Response Variability is Associated With Endothelial Dysfunction in Coronary Artery Disease Patients Receiving Dual Antiplatelet Therapy

Abstract

Introduction: Dual antiplatelet therapy with aspirin and a platelet P2Y12 ADP receptor antagonist is the cornerstone of treatment following percutaneous coronary intervention (PCI). Several clinical and genetic factors can cause suboptimal clopidogrel response. Hypothesis: Endothelial dysfunction affects clopidogrel response variability in subjects with stable coronary artery disease (CAD) after PCI. Methods: We consecutively enrolled 198 patients with stable CAD one month after successful PCI. All patients were receiving dual antiplatelet therapy (clopidogrel 75mg and aspirin 100mg/day). Platelet reactivity was measured by VerifyNow P2Y12 assay (Accumetrics, San Diego, CA). VerifyNow reports its results in P2Y12 reaction units (PRU) and the diagnostic cut-off value is 230. Endothelial function was evaluated by flow mediated dilation (FMD). Results: Patients with high on treatment platelet reactivity (32% of the study population), compared to subjects with low on treatment platelet reactivity, presented decreased FMD (4.35±2.22% vs. 5.74±3.29%, p=0.01). Moreover, an inverse association between endothelial function measurement and platelet reactivity (r=-0.24, p=0.001) was founded. Importantly, multivariate analysis after adjustment for age, gender and confounders revealed by the univariate analysis (left ventricle ejection fraction, body mass index, coronary lesion number) revealed that for every decrease in FMD by 1% there is an anticipated increased in P2Y12 reactive units by 10 units [b=-9.9, 95%CI(-19.0, -0.7), p=0.04]. Conclusions: Endothelial dysfunction is associated with clopidogrel response variability in patients after PCI receiving dual antiplatelet therapy. These findings shed some light on the mechanisms affecting individual platelet response to antiplatelet therapy and may explain the non-straight forward association between clopidogrel dose, platelet inhibition and cardiovascular outcome.