The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis.
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 of VASP 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.
Department of Cardiology, University Hospital Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. ruediger.blindt@post.rwth-aachen.de
Rüdiger
R
Blindt
Katja
K
Stellbrink
Anita
A
de Taeye
Robert
R
Müller
Paul
P
Kiefer
Eray
E
Yagmur
Christian
C
Weber
Malte
M
Kelm
Rainer
R
Hoffmann
D000244:Adenosine Diphosphate; D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation; D001241:Aspirin / Q000627:therapeutic use; D015815:Cell Adhesion Molecules / Q000097:blood*; D000077144:Clopidogrel; D017023:Coronary Angiography; 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*; D010766:Phosphorylation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests / Q000379:methods; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015607:Stents; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin