Soluble P-selectin level correlates with acetylsalicylic acid but not with clopidogrel response in patients with stable coronary artery disease after a percutaneous coronary intervention.

Background Impaired response to dual antiplatelet therapy is associated with worse cardiovascular outcome. Besides antiplatelet effects, there is evidence that both clopidogrel and acetylsalicylic acid (ASA) have anti-inflammatory properties. However, little is known about the relationship between platelet function and inflammation under dual antiplatelet therapy in patients with stable coronary artery disease. Purpose The purpose of the study was to investigate the correlation of platelet function with soluble (s)P-selectin and soluble (s)CD40L in patients undergoing elective percutaneous coronary intervention. Poor response to ASA and clopidogrel could lead to increased levels of inflammatory markers. Methods A total of 148 patients were included. Eighty percent of the patients were on 100 mg ASA and all patients were clopidogrel naive. They underwent percutaneous coronary intervention and received a loading dose of 600 mg clopidogrel. Platelet function was assessed by light transmittance aggregometry (LTA) and vasodilator-stimulated phosphoprotein analysis at baseline, 24 h after loading, and after 1 month of maintenance therapy, respectively. Plasma levels of sP-selectin and sCD40L were measured. To classify low responders to clopidogrel, patients were screened for genetic variants determining clopidogrel absorption and metabolization. Results sP-selectin levels correlated with LTA findings after stimulation with arachidonic acid (P = 0.012). Further, in addition to decreased platelet reactivity observed on LTA, lower sP-selectin levels were seen in patients under ASA therapy (P = 0.004). CYP2C19*2 allele carriers had a higher platelet reactivity after clopidogrel loading measured by adenosine diphosphate-induced aggregation in LTA (P = 0.008) and vasodilator-stimulated phosphoprotein phosphorylation (P = 0.035); however, there was no difference in the inflammatory markers. Multiple regression analysis showed that variables significantly related to sP-selectin plasma levels were sCD40L (P < 0.001), LTA after stimulation with arachidonic acid (P < 0.001), adenosine diphosphate (20 mu mol/l, P = 0.009), collagen (P < 0.001), and ejection fraction (P = 0.001). Conclusion sP-selectin was decreased in patients receiving ASA but did not reflect a CYP2C19*2-defined clopidogrel response. This underlines that sP-selectin is a useful marker for ASA, but not for clopidogrel response, in stable coronary artery disease. Coron Artery Dis 24:312-320 (c) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.