Author + information
- Received November 2, 2009
- Revision received December 23, 2009
- Accepted January 11, 2010
- Published online September 21, 2010.
- Laurent Bonello, MD⁎,†,
- Karim Harhouri, PhD†,
- Florence Sabatier, MD, PhD†,§,
- Laurence Camoin-Jau, MD, PhD†,‡,
- Laurent Arnaud, PhD‡,
- Karine Baumstarck-Barrau, MD∥,
- Omar Ait-Mokhtar, MD⁎,
- François Roubille, MD¶,
- Christophe Piot, MD, PhD¶,
- Nathalie Lesavre, MD#,
- Franck Paganelli, MD, PhD⁎ and
- Françoise Dignat-George, MD, PhD†,‡,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Françoise Dignat-George, INSERM UMR-S 608, UFR Pharmacie, 27 bd Jean Moulin, 13005 Marseille, France
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 P2Y12. 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 P2Y12 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 P2Y12 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.
All authors report that they have no relationships to disclose. Drs. Bonello and Harhouri contributed equally to this work.
- Received November 2, 2009.
- Revision received December 23, 2009.
- Accepted January 11, 2010.
- American College of Cardiology Foundation