Different methodologies for evaluating the effect of clopidogrel on platelet function in high-risk coronary artery disease patients

Background: Two point-of-care (POC) systems have been recently proposed as rapid tools with which to evaluate residual platelet reactivity (R-PR) in coronary artery disease (CAD) patients. Objectives and Methods: We compared Platelet Function Analyzer-100 (PFA-100) closure times (CTs) by collagen/adenosine 5-diphosphate (ADP) (C/ADP CT) cartridge and the Verify Now P2Y12 Assay (VerifyNow) with light transmission aggregation (LTA) induced by 2 and 10 mu mol L-1 ADP in 1267 CAD patients on dual antiplatelet therapy who underwent percutaneous coronary intervention. We also performed the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay by cytofluorimetric analysis in a subgroup of 115 patients. Results: Cut-off values for identifying RPR were: >= 54% and >= 66% for LTA induced by 2 and 10 mu mol L-1 ADP respectively, and >= 264 P2YI2 Reaction Units (PRU) for VerifyNow. The cut-off for PFA-100 C/ADP CT was >= 68 s. RPR was detected in 25.1% of patients by 2 mu mol L-1 ADP-induced LTA (ADP-LTA), in 23.2% by 10 mu mol L-1 ADP-LTA, in 24.4% by PFA-100, and in 24.7% by VerifyNow. PFA-100 results did not parallel those obtained with LTA. VerifyNow showed a significant correlation (rho = 0.62, P < 0.001) and significant agreement (k = 0.34, P < 0.001) with LTA induced by 2 mu mol L-1 ADP. The correlation was similar but the agreement was better between VerifyNow and 10 mu mol L-1 ADP-LTA (rho = 0.64, P < 0.0001; k = 0.43, P < 0.001). Significant relationships were found between VASP platelet reactivity index and both ADP-LTA and VerifyNow. PFA-100 C/ADP CT did not significantly correlate with any of the other assays. Conclusions: Our results show a significant correlation between LTA and VerifyNow but not the PFA-100 C/ADP assay. Clinical validation studies for POC systems are necessary.