Abstract 1032: High Clopidogrel Maintenance Dosing in Patients with Inadequate Platelet Inhibition: Functional Insights on Thienopyridine Usage According to Updated ACC/AHA/SCAI 2005 Guidelines for Percutaneous Coronary Interventions

Abstract

Background: Clopidogrel under-dosing is a cause of inadequate platelet inhibition. Inadequate clopidogrel-induced antiplatelet effects have been associated with an increased risk of stent thrombosis. Updated guidelines for percutaneous coronary interventions (PCI) recommend to increase the dose of clopidogrel to 150mg in high risk patients if <50% platelet inhibition is demonstrated. However, to date there are no studies which have evaluated the functional impact of this recommendation. The aim of this study was determine the functional impact of a 150mg maintenance dose of clopidogrel in patients with 50% platelet inhibition while in their steady state phase of dual antiplatelet therapy. Methods: Platelet inhibition was screened by means of the VerifyNow P2Y 12 assay in patients in a steady state phase of dual antiplatelet therapy. Patients with <50% platelet inhibition were treated with 150mg of clopidogrel for one-month. Adenosine diphosphate-induced aggregation using light transmittance aggregometry and P2Y 12 reactivity ratio determined by vasodilator-stimulated phosphoprotein-phosphorylation analysis were also performed. Results: A total of 32 patients were screened to identify 20 with <50% platelet inhibition. Platelet inhibition increased from 28.3±12% to 43.2±18% in patients treated with 150mg of clopidogrel (p=0.004; primary endpoint). All other functional measures also showed that a high maintenance dose of clopidogrel reduces platelet function (Table ) . The degree of platelet inhibition achieved following one-month treatment with high dose clopidogrel broadly varied and only eight (40%) patients yielded a degree of platelet inhibition ≥50%. Conclusions: The use of a 150mg maintenance dose of clopidogrel in high risk patients with <50% platelet inhibition increases platelet inhibition. However, the antiplatelet effects achieved are non-uniform and a considerable number of patients persist with elevated platelet function. Platelet function analysis pre and post high clopidogrel maintenance dose therapy