The Assessment of High Post-Clopidogrel Platelet Reactivity Using the Vasodilator-Stimulated Phosphoprotein Phosphorylation Index – Comparison with Light Transmittance Aggregometry.

Flow cytometric analysis of platelet reactivity index of vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) is a suitable test to evaluate the “high post-treatment platelet reactivity (HPPR)”. A reliable cut-off of VASP-P index is needed to identify the HPPR. However, an ideal cut-off identifying HPPR using the VASP-P index remains undetermined. We aimed to show the comparison between light transmittance aggregometry (LTA) and flow cytometric analysis of VASP-P index and assess the cut-offs of identifying HPPR using VASP-P index.

We enrolled consecutively patients undergoing percutaneous coronary intervention (PCI) in real clinical practice (n = 516). They all received clopidogrel and aspirin, performed LTA (5 and 20 μmol/l ADP-induced, and 1.6 nmol/l arachidonic acid (AA)-induced PR) and flow cytometric analysis of VASP-P index simultaneously and compared the different platelet measures. Based on previously suggested cut-offs, 5 μmol/l ADP-induced maximal platelet reactivity (PR_max) > 42.9%, 5 μmol/l ADP-induced PR_max > 50%, 20 μmol/l ADP-induced PR_max > 62%, 20 μmol/l ADP-induced PR_max > 64.5%, and 1.6 mmol/l AA-induced PR_max > 20%, the cut-offs of identifying HPPR using flow cytometric analysis of VASP-P were determined by receiver-operating characteristics (ROC) curve analysis.

Excellent correlations were observed between LTA with ADP-induced PR_max and flow cytometric analysis of VASP-P according to the ROC curve analyses. The ROC curve analyses demonstrated that 5 μmol/l ADP-induced PR_max > 42.9% could distinguish between patients with and without VASP-P index > 54.9% (area under curve [AUC] 0.926, 95% confidence interval (CI) 0.903–0.949, sensitivity 82.8%, and specificity 88.5%, p < 0.001) and 5 μmol/l ADP-induced PR_max > 50% could distinguish between patients with and without VASP-P index > 57.4% (AUC 0.937, 95% CI 0.914–0.961, sensitivity 91.5%, and specificity 85.2%, p < 0.001). ROC curve analysis demonstrated 20 μmol/l ADP-induced PR_max > 62% could distinguish between patients with and without VASP-P index > 55.2% (AUC 0.948, 95% CI 0.927–0.969, sensitivity 95.7%, and specificity 87.3%, p < 0.001) and 20 μmol/l ADP-induced PR_max > 64.5% could distinguish between patients with and without VASP-P index > 55.9% (AUC 0.925, 95% CI 0.900–0.951, sensitivity 88.3%, and specificity 83.0%, p < 0.001), respectively. However, fair correlation was observed between AA-induced PR_max and VASP-P index and 1.6 nmol/l AA-induced PR_max > 20% could distinguish between patients with and without VASP-P index > 52.4% (AUC 0.761, 95% CI 0.719–0.802, sensitivity 68.5%, and specificity 72.7%, p < 0.001). We defined the ideal threshold of VASP-P index > 56%. The VASP-P index > 56% showed a substantial agreement with 5 μmol/l and 20 μmol/l ADP-induced PR_max (Table 1). However, VASP-P index > 56% showed a moderate agreement with 1.6 nmol/l AA)-induced PR_max > 20% (Table 1).

There are significant correlations between the suggested cut-offs of HPPR. Because VASP-P index > 56 is well matched with 5 μmol/l ADP-induced PR_max > 42.9%, 5 μmol/l ADP-induced PR_max > 50%, 20 μmol/l ADP-induced PR_max > 62%, and 20 μmol/l ADP-induced PR_max > 64.5%., it might suggest that VASP-P index > 56 has a practical implication for stratification of high-risk ischemic events.

No relevant conflicts of interest to declare.