Abstract 2041: Low P2Y12-Specific Platelet Inhibition in Clopidogrel-Treated Patients with Coronary Artery Disease is Common and not Reliably Detected by Conventional Aggregation Tests
Background: Incomplete inhibition of P2Y12-mediated platelet activation during clopidogrel treatment has been associated with increased cardiovascular morbidity and mortality after percutaneous coronary intervention. This study aimed to investigate the incidence of impaired individual clopidogrel-responsiveness using a P2Y12-specific and pre-treatment-independent assay in a real world situation.
Methods: 100 consecutive patients with coronary artery disease on clopidogrel treatment (> 5 days including a loading dose of at least 300 mg) were screened for response to ADP-induced platelet signalling. We assessed the vasodilator-stimulated phosphoprotein-based platelet reactivity index (PRI) as the only P2Y12-specific assay to determine clopidogrel responsiveness. Insufficient inhibition of P2Y12 by clopidogrel was defined as a PRI >50% based on previous studies indicating increased risk of stent thrombosis under this condition. The results were compared with conventional assays to assess ADP-induced P-selectin surface-expression and conventional turbinometric platelet aggregation to several concentrations of ADP.
Results: Clopidogrel significantly lowered functional platelet reactivity in patients with coronary artery disease compared to untreated patients. However, insufficient individual response to treatment predisposing for adverse events and therefore previously described as “non-response” was diagnosed in 69% of clopidogrel-treated patients using PRI. Conventional aggregation failed to detect insufficient P2Y12-inhibition in 1/3of patients with a PRI>50%.
Conclusion: Using the PRI as the only P2Y12-specific assay to evaluate the treatment effect of clopidogrel in patients with coronary artery disease, insufficient P2Y12-inhibition was present in the majority of patients in a real-world scenario. Insufficient P2Y12-inhibition could not be reliably detected by conventional aggregation More prospective studies are needed to evaluate the influence of the high prevalence of incomplete clopidogrel responsiveness to major adverse cardiac events.