Multiple genetic mutations increase the risk of thrombosis associated with clopidogrel after percutaneous coronary intervention.

The effects of different combinations of mutations in the genes CYP2C19, PON1 and ABCB1 on the effectiveness and safety of dual antiplatelet therapy in patients who undergo percutaneous coronary intervention (PCI) are unclear. In total, 263 Chinese Han patients receiving 75 mg clopidogrel and 100 mg aspirin daily for 12 months after PCI were enrolled in this study. ADP-induced platelet aggregation rates, thrombosis and bleeding risk were used to compare clopidogrel responses among the patients. Only 3.4% of patients had no mutations in CYP2C19, PON1 or ABCB1, and 74% of patients who chose to be genetically tested carried more than two mutations in these genes. High ADP-induced platelet aggregation rates in patients receiving clopidogrel and aspirin after PCI were associated with mutations in CYP2C19, PON1 and ABCB1. Patients with double or triple genetic mutations in CYP2C19, PON1 or ABCB1 had a higher risk of thrombosis within 18 months of follow-up. We conclude that multiple genetic polymorphisms influence platelet reactivity, bleeding and thrombosis risk during dual antiplatelet therapy after PCI.