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SummaryObjectivesWe investigated the agreement between different platelet tests to identify clopidogrel non response.BackgroundBiological definition of clopidogrel non response remains controversial. Different platelet tests have been linked with recurrent ischemic events and proposed for daily practice.MethodsWe prospectively investigated the agreement of platelet tests to isolate clopidogrel non response in patients receiving high 150mg clopidogrel maintenance dose after coronary stenting. Clopidogrel response was assessed with ADP-induced aggregation (ADP-Ag) (non response if >70%), Platelet reactivity index VASP (PRI VASP) (non response if >50%) and Verify Now Point-of-care assay (VN) (non response if PRU>240 AU).ResultsSeventy consecutive patients were included. The rates of non-responders were respectively: 13% (n=9) with the ADP-Ag, 39% (n=27) with the PRI VASP and 33% (n=23) with the VN. We observed significant correlation between different platelet tests assessing clopidogrel response: r=0.55 (p

Background La thrombose et l’inflammation sont impliquees dans l’initiation et la progression de la lesion atheromateuse. Ainsi, de nombreuses cellules du compartiment vasculaire jouent un role cle dans la pathogenese de la maladie coronarienne et ses complications. Determiner precisement l’etat d’activation de ces differents types cellulaires pourrait contribuer a identifier les patients coronariens a haut risque d’evenements recurrents. Les microparticules (MP) sont des fragments de membrane desormais reconnus comme marqueurs fiables de l’activation et de l’apoptose cellulaires. Objectif Notre objectif a ete de determiner si les taux de MP issues de differents types cellulaires etaient associes a la severite des lesions atheromateuses et a la recurrence d’evenements cardiovasculaires chez des patients coronariens. Methodes et Resultats Les taux plasmatiques de MP ont ete mesures par cytometrie en flux chez 172 patients en attente de coronarographie a l’hopital de la Timone. 77 patients (46 %) ont beneficie d’une pose de stent et ont ete suivis durant 1 mois. 12 evenements recurrents ont ete rapportes pendant la periode de suivi. Dans la cohorte totale, les taux de MP positives pour le marqueur d’activation leucocytaire CD11b (MPCD11b+) etaient significativement plus eleves chez les patients traites par des statines (p = 0,001) et chez les patients ayant une fraction d’ejection preservee (p = 0,02). Les taux de MPCD11b+ etaient significativement mais negativement associes a l’etendue des lesions atheromateuses coronaires evaluee par les donnees angiographiques et par le Syntax Score, ceci meme apres ajustement sur le traitement par les statines et sur la fraction d’ejection (p = 0,005). Au sein de la population stentee, les taux de MPCD11b+ etaient significativement inferieurs chez les patients ayant presente un evenement recurrent (p = 0,0001). Cette difference restait significative apres ajustement sur le Syntax Score, sur la fraction d’ejection et sur le traitement par des statines (p = 0,03). Conclusion Les MPCD11b+ sont un marqueur biologique qui permet d’identifier les patients coronariens a haut risque de recurrence independamment de la severite des lesions observees lors de la coronarographie.

Objectives The aim of the study was to evaluate the impact of CYP2C19*17 on Platelet Response to Clopidogrel in patients suffering from Non-ST Elevation Acute Coronary Syndrome (NSTE ACS). Background Clopidogrel is activated by cytochrome P450 (CYP) to generate an active metabolite that inhibits platelets through irreversible binding to the platelet P2Y12 receptor. We have shown that CYP2C19*2 is associated with a low platelet response to clopidogrel (Am J Cardiol 2008), which has been demonstrated to predict adverse events in patients suffering from NSTE ACS. Recently, a novel allelic variant (CYP2C19*17) encoding an ultrarapid enzyme activity has been described. Results We evaluated in 449 patients with non-ST elevation ACS after the administration of a loading dose of 600 mg clopidogrel, the impact of CYP2C19*17 on platelet response to clopidogrel assessed by vasodilator stimulated phosphoprotein phosphorylation index (PRI VASP). No significant deviations from Hardy-Weinberg equilibrium were observed for this genetic variant. The observed frequency of the CYP2C19*17 allele was 20 %. The CYP2C19*17 allele was significantly associated with VASP, both in recessive (p =0.02) and codominant (p =0.0073) models. The CYP2C19*17 allele carriers (extensive metabolizers) exhibited the lowest PRI VASP (mean ± SD = 49.7±23.7 vs 55.9±22.8), testifying a better platelet response to clopidogrel. The interaction between the CYP2C19*2 (decrease in platelet response to clopidogrel) an the CYP2C19*17 allele (increase in platelet response to clopidogrel) was not significant. Conclusion The present data suggest that the CYPC19*17 allele influences platelet response to clopidogrel in patients with NSTE ACS, independently from the CYPC19*2 allele.

AimsDiabetic patients have a higher prevalence of inadequate platelet response to Clopidogrel. However, determinants of this low response remain uncertain.Methods and ResultsWe analyzed ADP-induced platelet aggregation (ADP-Ag), and Platelet Reactivity Index of Vasodilatator- Stimulated Phosphoprotein (PRI VASP) in 124 diabetic patients treated with Clopidogrel, and repeated them after glycemic optimization in 15 uncontrolled patients.Platelet tests did not correlate with glycemic control and did not change after glycemic optimization. Type 2 diabetics had higher ADP-Ag and PRI VASP than type 1 (49±19 vs 33±19 %, p = 0.008; 62±16 vs 48±27 %, p = 0.02, respectively). On adjustment for studied variables ADP-Ag but not PRI VASP remained statistically associated with the type of diabetes (p = 0.007; p=0.11 respectively). Also fibrinogen was an independent predictor of ADP-Ag and clopidogrel non responders had elevated plasma fibrinogen, compared with responders: 8.2 ± 0.5 versus 3.8 ± 0.1g/L (p