Comparison of VerifyNow-P2Y.sub.12 test and Flow Cytometry for monitoring individual platelet response to clopidogrel. What is the cut-off value for identifying patients who are low responders to clopidogrel therapy?

Background Dual anti-platelet therapy with aspirin and a thienopyridine (DAT) is used to prevent stent thrombosis after percutaneous coronary intervention (PCI). Low response to clopidogrel therapy (LR) occurs, but laboratory tests have a controversial role in the identification of this condition. Methods We studied LR in patients with stable angina undergoing elective PCI, all on DAT for at least 7 days, by comparing: 1) Flow cytometry (FC) to measure platelet membrane expression of P-selectin (CD62P) and PAC-1 binding following double stimulation with ADP and collagen type I either in the presence of prostaglandin (PG) E.sub.1 ; 2) VerifyNow-P2Y.sub.12 test, in which results are reported as absolute P2Y.sub.12 -Reaction-Units (PRU) or % of inhibition (% inhibition). Results Thirty controls and 52 patients were analyzed. The median percentage of platelets exhibiting CD62P expression and PAC-1 binding by FC evaluation after stimulation in the presence of PG E.sub.1 was 25.4% (IQR: 21.4-33.1%) and 3.5% (1.7-9.4%), respectively. Only 6 patients receiving DAT (11.5%) had both values above the 1.sup.st .sup.quartile of controls, and were defined as LR. Evaluation of the same patients with the VerifyNow-P2Y.sub.12 test revealed that the area under the receiver-operating-characteristic (ROC) curve was 0.94 (95% CI: 0.84-0.98, p [less than] 0.0001) for % inhibition and 0.85 (0.72-0.93, p [less than] 0.005) for PRU. Cut-off values of [less than or equal to] 15% inhibition or > 213 PRU gave the maximum accuracy for the detection of patients defined as having LR by FC. Conclusion In conclusion our findings show that a cut-off value of [less than or equal to] 15% inhibition or > 213 PRU in the VerifyNow-P2Y.sub.12 test may provide the best accuracy for the identification of patients with LR.