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. Aim.- 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)] x 100, 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%. Conclusion. - Assessment of VASP index in ACS patients identifies low responders to clopidogrel who are at increased risk of recurrent cardiovascular events. (c) 2008 Elsevier Masson SAS. All rights reserved.