P2Y12 gene H2 haplotype is not associated with increased adenosine diphosphate-induced platelet aggregation after initiation of clopidogrel therapy with a high loading dose

Abstract

A large variability in the antiplatelet response to clopidogrel has been consistently reported. Recently, a P2Y12 haplotype was shown to be associated with enhanced adenosine diphosphate (ADP)-induced platelet aggregation in healthy volunteers. The aim of this study was to test in patients (n = 416) scheduled for coronary artery stenting whether P2Y12 haplotype H2 carriage is associated with increased ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. Blood was drawn from the arterial sheath at least 2 h after administration of 100 mg aspirin and 600 mg clopidogrel. ADP-induced platelet aggregation was assessed in platelet-rich plasma with light-transmission aggregometry. P2Y12 haplotypes (H1/H2) and P2Y12 C32T genotypes were determined with TaqMan assays. Haplotype combinations and genotypes were not associated with parameters of ADP-induced platelet aggregation after administration of a 600 mg loading dose of clopidogrel. Maximal ADP (5 mumol/l)-induced platelet aggregation was similar in patients carrying haplotype H2 and homozygous carriers of haplotype H1 (43.9 +/- 21.4 versus 43.2 +/- 21.1%, respectively; P = 0.77). Carriage of P2Y12 H2 haplotype does not seem to affect the platelet response to a 600 mg loading dose of clopidogrel in coronary artery disease patients prior to stenting.

Coexisting Polymorphisms of P2Y12 and CYP2C19 Genes as a Risk Factor for Persistent Platelet Activation With Clopidogrel

“…9,10,13-15 von Beckerath et al used light-transmittance aggregometry testing in 416 patients scheduled for coronary artery stenting who were administered a single dose of 600 mg of clopidogrel, 9 and Angiolillo et al used light-transmittance aggregometry and whole blood flow cytometry in 36 patients listed for elective PCI. 13,14 Smith et al used ADP-induced optical aggregometry, whole-blood single platelet counting aggregometry and flow-cytometric analysis of platelet P-selectin expression in 55 patients undergoing elective PCI and on in additional group of 83 patients on long-term clopidogrel treatment.…”

Variable Platelet Response to Aspirin and Clopidogrel in Atherothrombotic Disease

“…87 An effect on clopidogrel response, however, has not been discerned. 88 Correlation between carriage of the human platelet alloantigen membrane GP IIIa variant (PLA 2 ), and the antithrombotic effect of clopidogrel in patients with CAD has also been explored. However, data from these studies are conflicting.…”

Variability of clopidogrel response in patients with type 2 diabetes mellitus

“…Clopidogrel has proven clinical efficacy in both short-and long-term outcomes in patients with ACS and those undergoing PCI. 45,[47][48][49]62 However, accumulating data from pharmacodynamic studies, from epidemiological analyses, and from DM subanalyses from clinical outcomes trials suggest a clinically relevant suboptimal clopidogrel response in at least some patients with DM. The exact mechanism underpinning the variability of clopidogrel response among patients with DM has yet to be fully elucidated, but the majority of evidence suggests that the underlying mechanism is likely attributable at least in part to decreased circulating active metabolite, whether by impaired absorption and/or impaired conversion of prodrug to active metabolite and/or increased rate of hydrolysis of the active metabolite.…”