Flow cytometric assessment of vasodilator-stimulated phosphoprotein: prognostic value of recurrent cardiovascular events after acute coronary syndromes.
BACKGROUND
Clopidogrel fails to elicit an adequate antiplatelet response in 4-30% of patients. Assessing the phosphorylation of intraplatelet vasodilator-stimulated phosphoprotein (VASP) is an easy and reliable method of evaluating biological response to clopidogrel.


OBJECTIVE
To assess the prognostic value of clopidogrel in patients with an acute coronary syndrome (ACS) without persistent ST-segment elevation.


METHODS
We studied clopidogrel response prospectively in 49 patients treated with a loading dose of 300 mg clopidogrel followed by a maintenance dose of 75 mg/day. VASP index was calculated from the median fluorescence intensity (MFI) of samples incubated with prostaglandin E1 (PGE1) and adenosine diphosphate according to the formula [(MFI(PGE1)-MFI(PGE1-ADP))/MFI(PGE1)]x100, and was determined at baseline and at days 1 and 4 after starting clopidogrel. We correlated VASP index with occurrence of recurrent cardiovascular events over six-month follow-up.


RESULTS
There was a significant stepwise decrease in VASP index from baseline (86+/-6%) to day 1 (71+/-13%) and day 4 (61+/-16%; p<0.001) with marked interindividual variability. Patients who experienced recurrent cardiovascular events displayed a higher VASP index compared with those free of events (76+/-3% versus 59+/-16%, p=0.006). Five of six recurrent events occurred in patients in the upper quartile of VASP index measured at day 4. The best cut-off of platelet reactivity index of VASP to predict high-risk ACS patients was at 70%.


CONCLUSIONS
Assessment of VASP index in ACS patients identifies low responders to clopidogrel who are at increased risk of recurrent cardiovascular events.
Cayla
Guillaume
G
Départment de cardiologie, hôpital Arnaud-de-Villeneuve, CHU de Montpellier, 34295 Montpellier, France. guillaumecayla@free.fr
Macia
Jean-Christophe
JC
Rabesandratana
Herisoa
H
Roubille
François
F
Gervasoni
Richard
R
Pasquié
Jean-Luc
JL
Barbotte
Eric
E
Schved
Jean-François
JF
Leclercq
Florence
F
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000097:blood*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000097:blood*; D008875:Middle Aged; D010750:Phosphoproteins / Q000097:blood*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D012008:Recurrence; D012680:Sensitivity and Specificity; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D017211:Treatment Failure; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin