Identification of low responders to a 300-mg clopidogrel loading dose in patients undergoing coronary stenting

Background: Although patients undergoing coronary stenting routinely receive dual antiplatelet treatment to reduce the risk of stent thrombosis, this undesired event still occurs. A suboptimal response to clopidogrel treatment (low responders) has been suggested to contribute to stent thrombosis. In the present study, platelet function profiles were assessed in patients undergoing coronary stenting receiving a standard 300-mg clopidogrel loading dose with the aim to identify low clopidogrel responders. Materials and methods: Platelet aggregation was assessed by light transmittance aggregometry following 6 muM ADP stimuli in 48 patients before and 10 min, 4 and 24 h after receiving clopidogrel front-loading. Patients having greater than or equal to40% inhibition of platelet aggregation 24 h after clopidogrel administration were defined as normal responders, whereas those having <40% inhibition were low responders. Glycoprotein (GP) IIb/IIIa activation and P-selectin expression were assessed by whole blood flow cytometry following 2 muM ADP stimuli at the same time points. Platelet function profiles were compared between normal and low clopidogrel responders. Results: Twenty-seven patients (56%) were normal responders and 21 (44%) low responders. Baseline GP IIb/IIIa activation was higher in low responders (74.6 +/- 16.6% vs. 58.2 +/- 24.5%, p=0.03). Although GP IIb/IIIa activation reduced following clopidogrel front-loading in both groups, it remained increased among low responders at 24 h (58.6 +/- 21.3% vs. 40.2 +/- 28.7%, p=0.05) and during the overall study time course (p=0.02). There were no differences in P-selectin expression. Conclusions: A considerable proportion of patients have an early suboptimal response to a 300-mg clopidogrel loading dose. An increased GP IIb/IIIa activation before intervention may identify this group of patients suggesting the use of a more aggressive antithrombotic treatment in these individuals. (C) 2004 Elsevier Ltd. All rights reserved.