Impact of P2Y12-ADP receptor polymorphism on the efficacy of clopidogrel dose-adjustment according to platelet reactivity monitoring in coronary artery disease patients

Introduction: High on-treatment platelet reactivity (HTPR) after clopidogrel loading dose (LD) is associated with a high risk of thrombotic events after percutaneous coronary intervention(PCI). We have demonstrated that HTPR could be overcome in the majority of cases using LD adjustment resulting in an improved clinical outcome. However this strategy failed in nearly 10% of patients with HTPR. We aimed to determine if P2Y12-ADP receptor polymorphisms were associated with failed dose adjustment. Materiel and method: Forty-three patients undergoing PCI were included in this prospective study. A VASP index >= 50% after a 600 mg LD of clopidogrel defined HTPR. Dose adjustment was performed according to PR monitoring to reach a VASP index <50%. Genetic polymorphism of the P2Y12-ADP receptor was determined by direct sequencing. Results: Patients with successful dose-adjustment (SDA) (n=33) and failed (FDA) (n=10) dose-adjustment groups were compared. The 2 groups were similar in terms of cardiovascular risk factors including diabetes mellitus (SDA vs FDA: 42 vs 20%; p=0.3). The prevalence of the H2 allele of the P2Y12-ADP receptor was also similar between the 2 groups (p=0.3). The H2 allele was found in 6 patients which are all included in the SDA group. After the first 600 mg loading dose of clopidogrel, patients carrying at least one H2 allele had similar VASP index compared to those carrying two copies of the wild type allele (H1) (SDA vs FDA: 44.9 +/- 14.9 vs 43.5 +/- 10%; p=0.8). Conclusion: The present study suggests that the H2 allele of the P2Y12-ADP receptor is not involved in clopidogrel failed dose adjustment according to platelet reactivity monitoring. (C) 2009 Published by Elsevier Ltd.