Abstract 2396: Consistent Platelet Inhibition After Chronic Maintenance Dose Clopidogrel Therapy Among 359 Compliant Outpatients with Documented Ischemic Stroke and Coronary Artery Disease
Objective: To describe the responses of ex vivo measures of platelet aggregation and activation to long-term chronic clopidogrel therapy in a large population of outpatients after coronary stenting, or ischemic stroke.
Background: Numerous reports have dichotomized responses after clopidogrel using varying definitions and platelet tests in patients immediately following acute vascular events. However, no large study assessed the platelet characteristics in outpatients treated chronically over 30 days with the maintenance (75mg/daily) dose of clopidogrel.
Methods: Secondary post-hoc analyses of a dataset consisting of presumably compliant patients after coronary stenting (n=237), and documented ischemic stroke (n=122) treated with clopidogrel and aspirin combination antiplatelet therapy.
Results: The mean duration of treatment was 5.8 months (1–21 months range). Every patient exhibited a significant inhibition of ADP-induced platelet aggregation (52.9%, mean; 36%–70% range) compared to the pre-clopidogrel measures. Inhibition of aggregation strongly correlates with the diminished PECAM-1 (r=0.75), GPIIb/IIIa (r=0.62), and PAR-1 receptor (r=0.71) expression. None of the patients developed hypo-responsiveness (reduction from the baseline < 15%), or profound inhibition (residual platelet activity < 10%).
Conclusions: In contrast with the wide response variability which exists in acute setting, chronic long-term therapy with clopidogrel is associated with consistent, and much less variable platelet inhibition. Lack of non-response, and/or profound inhibition with clopidogrel allow to maintain a delicate balance between proven efficacy and acceptable bleeding risks for the long-term secondary prevention in outpatients after documented ischemic stroke and coronary artery disease.