Abstract 12123: Impact of Endothelial Dysfunction on Residual Platelet Aggregability after Dual Antiplatelet Therapy with Aspirin and Clopidogrel in Stable Patients with Coronary Artery Disease
Background: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is widely applied for patients treated by coronary stents. Higher residual platelet reactivity (Hi-RPR) after DAPT is associated with increasing cardiovascular events. Endothelial function plays an important role on the platelets reactivity in vivo. We hypothesized that endothelial dysfunction could be associated with Hi-RPR in patients with coronary artery disease (CAD).
Methods: We identified CYP2C19 genotypes in stable CAD patients and enrolled 36 patients without CYP2C19 *2 or *3 loss-of-function allele to minimize genetic effects on Hi-RPR. All patients were under aspirin treatment for more than 7 days. 18 patients already received clopidogrel (75mg) for more than 7 days and 19 patients were treated with a loading dose of clopidogrel (300mg) ≥24 hours before the following tests. Platelet aggregability was assessed as P2Y12 reaction unit (PRU) by VerifyNow System and Hi-RPR was defined as PRU≥230. Plasma levels of B-type natriuretic peptide (BNP) were measured. Peripheral endothelial function was assessed as reactive hyperemia index (RHI) by reactive hyperemia peripheral arterial tonometry.
Results: 21 patients exhibited Hi-RPR (age 68.9±7.7, men 66.7%). There were no significant differences in clinical characteristics between Hi-RPR and others. RHI was significantly lower in Hi-RPR patients than others (0.42±0.15 vs. 0.56±0.17, p=0.03). BNP levels were significantly higher in Hi-RPR patients (BNP; 57.5 [21.2-106.8] vs. 35.3 [16.5-52.7] pg/mL; p=0.03). Linear regression analysis demonstrated significant negative correlation between RHI and PRU (r=-0.351, p=0.036). By univariate logistic regression analysis, RHI [odds ratio (OR); 0.62, 95% confidence interval (CI) 0.40-0.97; p=0.04] was significantly associated with Hi-RPR, but BNP was not. Backward stepwise multivariate logistic regression analysis indicated RHI was independently associated with Hi-RPR (OR; 0.58, 95% CI 0.35-0.97, p=0.04).
Conclusion: In stable CAD patients without CYP2C19 *2 or *3 loss-of-function allele, endothelial function was significantly impaired in patients with Hi-RPR. Endothelial dysfunction could be a modifiable and important factor correlated with Hi-RPR after DAPT.
- © 2012 by American Heart Association, Inc.