Level of adenosine diphosphate receptor P2Y12 blockade during percutaneous coronary intervention predicts the extent of endothelial injury, assessed by circulating endothelial cell measurement.

Abstract:

OBJECTIVES:We aimed to investigate whether clopidogrel-induced inhibition of platelet reactivity could reduce the level of circulating endothelial cells (CEC), reflecting the endothelial injury induced by percutaneous coronary intervention (PCI). BACKGROUND:Clopidogrel loading dose before percutaneous coronary angioplasty (PCI) reduces platelet activation through a selective and irreversible blockade of the adenosine diphosphate (ADP) receptor P2Y(12). The impact of clopidogrel on endothelial cells has been scarcely studied. METHODS:A total of 149 patients undergoing PCI for stable angina were enrolled. Levels of CEC were measured at baseline (H0) and 6 (H6) and 24 (H24) h after the procedure using a CD146-based immunomagnetic separation assay. The CEC delta-change (CEC at H6 - CEC at H0) was analyzed according to ADP receptor P2Y(12) blockade, assessed by a vasodilator-stimulated phosphoprotein (VASP) assay after a 600-mg loading dose of clopidogrel. RESULTS:The PCI induced a significant rise in CEC levels 6 h after the procedure. The CEC peak value was significantly higher in patients with high on-treatment platelet reactivity (VASP index ≥50%: 59.6 ± 27.5 cells/ml) as compared with good responders (VASP index <50%: 27 ± 22 cells/ml; p = 0.04). The endothelial injury, assessed by CEC delta-change between H6 and H0, was significantly higher in the high on-treatment platelet reactivity group compared with the good responders group (52.6 ± 25.6 vs. 18.6 ± 23.5, respectively; p < 0.001) and correlated with the VASP index (r = 0.59; p < 0.001). In multivariate analysis, VASP group, the number of diseased vessels, and the number of implanted stents independently predicted the endothelial injury (p < 0.001). CONCLUSIONS:Optimal ADP receptor P2Y(12) blockade reduces the endothelial injury during PCI. This protective effect of clopidogrel on endothelial cells could add to the clinical benefit associated with this drug.

journal_name

J Am Coll Cardiol

authors

Bonello L,Harhouri K,Sabatier F,Camoin-Jau L,Arnaud L,Baumstarck-Barrau K,Ait-Mokhtar O,Roubille F,Piot C,Lesavre N,Paganelli F,Dignat-George F

doi

10.1016/j.jacc.2010.01.072

subject

Has Abstract

pub_date

2010-09-21 00:00:00

pages

1024-31

issue

13

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(10)02575-1

journal_volume

56

pub_type

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