PIA polymorphism and platelet reactivity following clopidogrel loading dose in patients undergoing coronary stent implantation

The pI(A) polymorphism (Leu33Pro) of the platelet glycoprotein (GP) Ilia gene has been suggested to play an important role in coronary thrombosis. In vitro studies have shown differences for this polymorphism in platelet sensitivity towards antiplatelet drugs (aspirin and abciximab), suggesting a pharmacogenetic modulation. The aim of the study was to assess the modulatory effect of the pI(A) polymorphism on clopidogrel-induced antiplatelet effects in 38 patients undergoing coronary stent implantation receiving a 300 mg clopidogrel loading-dose. Platelet reactivity was assessed as GPIIb/IIIa activation and P-selectin expression in platelets stimulated with 2 mumol/l adenosine diphosphate using whole blood flow cytometry. The distribution of the homozygous pI(A1/A1) and heterozygous pI(A1.A2) genotypes were 74 and 26%, respectively. pI(A2) carriers had a higher degree of GPIIb/IIIa activation (P = 0.05) and P-selectin expression (P = 0.02) during the overall study time course and a lower antiplatelet effect to a 300 mg clopidogrel loading-dose up to 24 h following intervention (P< 0.05). In conclusion, the pI(A) polymorphism of the GPIIIa gene modulates platelet reactivity towards clopidogrel front loading in patients undergoing coronary stenting. This suggests the need for individualized antithrombotic regimens to optimally inhibit platelet reactivity. (C) 2004 Lippincott Williams Wilkins.