Identification of poor response to P2Y12 inhibitors in ACS patients with a new ELISA-based vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay.
A new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.
Gilles Montalescot, MD, PhD, Bureau 236, Institut de Cardiologie,, Pitié-Salpêtrière University Hospital, 47-83 boulevard de l'Hôpital, 75013 Paris, France, Tel: +33 142163006, Fax: +33 142162931, E-mail: gilles.montalescot@psl.aphp.fr.
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J
Abtan
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Silvain
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Kerneis
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O'Connor
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Barthélémy
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JB
Vignalou
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Beygui
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Brugier
J-P
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Collet
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Montalescot
D054058:Acute Coronary Syndrome / Q000097:blood / Q000175:diagnosis*; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002469:Cell Separation; D000077144:Clopidogrel; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism*; D010879:Piperazines / Q000008:administration & dosage*; D010979:Platelet Function Tests; D000068799:Prasugrel Hydrochloride; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013876:Thiophenes / Q000008:administration & dosage*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000098662:Vasodilator-Stimulated Phosphoprotein
D000925:Anticoagulants; D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010879:Piperazines; D013876:Thiophenes; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine
ACS; ELISA; VASP; flow cytometry; platelet reactivity