Aspirin and clopidogrel drug response in patients undergoing percutaneous coronary intervention - The role of dual drug resistance

OBJECTIVES We sought to evaluate the response to clopidogrel among aspirin-resistant versus aspirin-sensitive patients undergoing percutaneous coronary intervention (PCI). BACKGROUND Wide variability has been reported in response to aspirin and clopidogrel. There are limited data on the simultaneous responses to both drugs. METHODS Elective PCI patients (n = 150) who received aspirin for l week but not clopidogrel were included. All patients received bivalirudin during PCI. Blood samples were drawn at baseline and 20 to 24 h after a 300-mg clopidogrel dose. Aspirin resistance was defined by >= 2 of 3 criteria: rapid platelet function analyzer-ASA score >= 550, 5 mu mol/l adenosine diphosphate (ADP)-induced aggregation >= 70%, and 0.5 mg/ml arachidonic acid-induced aggregation >= 20%. Clopidogrel resistance was defined as baseline minus post-treatment aggregation <= 10% in response to 5 and 20 mu mol/l ADP. RESULTS Nineteen (12.7%) patients were resistant to aspirin and 36 (24%) to clopidogrel. Nine (47.4%) of the aspirin-resistant patients were also clopidogrel resistant. Aspirin-resistant patients were more likely to be women and have diabetes than were aspirin-sensitive patients. They also had lower response to clopidogrel, assessed by platelet aggregation and activation markers (flow cytometry-determined PAC-1 binding and P-selectin expression). Elevation of creatine kinase-myocardial band after stenting occurred more frequently in aspirin-resistant versus aspirin-sensitive patients (38.9% vs. 18.3%; p = 0.04) and in clopidogrel-resistant versus clopidogrel-sensitive patients (32.4% vs. 173%; p = 0.06). CONCLUSIONS Aspirin-resistant patients as a group have reduced response to clopidogrel. Furthermore, we have identified a unique group of dual drug-resistant patients who may be at increased risk for thrombotic complications after PCI.