The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis
Rüdiger Blindt 1, Katja Stellbrink 1, Anita de Taeye 1, Robert Müller 2, Paul Kiefer 2, Eray Yagmur 2, Christian Weber 3, Malte Kelm 1, Rainer Hoffmann1
1 Department of Cardiology, University Hospital Aachen, Germany; 2 Institute of Clinical Chemistry and Pathobiochemistry, University Hospital Aachen, Germany; 3 Institute of Cardiovascular Molecular Research (IMCAR), University Hospital Aachen, Germany
clopidogrel, VASP phosphorylation, Stent thrombosis, platelet aggregometry
Low-response to the P2Y12 adenosine diphosphate (ADP)-receptor antagonist clopidogrel was suggested to correspond to a higher incidence of stent thrombosis (ST).This prospective observational study assessed the capability of two platelet function assays, e.g. direct measurement of the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and ADP-induced platelet aggregation for definition of the individual risk to develop ST. Ninety-nine patients with an elevated high risk to develop ST were enrolled. All patients received a dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg clopidogrel during an observation period of six months. Flow cytometry of VASP phosphorylation and densitometrically-determined measurement of ADP-induced platelet aggregation was performed 72–96 hours after stent implantation.These data were related to angiographically confirmed ST. Nine patients suffered from angiographically confirmed ST (9.1%).The meanVASP-platelet reactivity indices (VASP-PRI) and values for ADP-induced platelet aggregation in the ST group were significantly higher (60.8 ± 13.0 and 60.9 ± 13.1, respectively) compared to patients without ST (41.3 ± 14.0 and 50.8 ± 14.4, P<0.001 vs. 0.048, respectively). There was a fair correlation between both methods using non-linear regression analysis (r=0.332). In a multivariate analysis, VASP was the only independent predictor of ST and was superior to previously identified angiographic parameters. Receiver- operator characteristic (ROC) curve analysis revealed a cut-off value for VASP-PRI of <48% to be associated with low risk of ST. In conclusion, determination ofVASP phosphorylation is superior to conventional platelet aggregometry and angiographic parameters for assessing the risk of ST. Patients with a VASP-PRI >48% seem to have a significantly increased risk.