Detecting a thienopyridine effect by platelet reactivity assessment and its implications for risk stratification

Abstract

Summary: Background: On-treatment platelet reactivity (OTR) is a predictor of clinical outcomes in patients receiving thienopyridine therapy. Objective: To assess whether point-of-care platelet reactivity testing can discriminate between patients who have and have not received a thienopyridine. Patients/Methods: This was an analysis of a randomized, multicenter, pharmacodynamic trial. Subjects with coronary artery disease treated with aspirin were randomly assigned to clopidogrel 75 mg daily or prasugrel 10 mg daily for 7 days. Platelet reactivity assessment with the VerifyNow P2Y12 test was performed before study drug admistration and 24 h after the final dose. Optimal cut-offs for a detectable drug effect were identified by the use of receiver operating characteristic curve analysis. Results: A total of 54 subjects were enrolled and completed the study. The c-statistic for the identification of a thienopyridine effect was highly significant (0.93, P < 0.001), including for the clopidogrel and prasugrel groups considered separately (P < 0.001 for both). The optimal cut-off was < 213 P2Y12 reaction units (PRU), which provided a sensitivity of 80% and a specificity of 98%. This cut-off provided a sensitivity of 58% and a specificity of 100% for a clopidogrel effect, and a sensitivity of 100% and specificity of 96% for a prasugrel effect. Conclusions: OTR of < 213 PRU is highly specific for exposure to either clopidogrel or prasugrel. This may be useful in the management of thienoypridine-treated patients who require surgery. Furthermore, this diagnostic cut-off is similar to levels of OTR that have been associated with ischemic events in thienopyridine-treated patients, supporting the contention that a lack of drug effect is the mechanistic basis for the prognostic relationship between OTR and clinical outcomes. © 2014 International Society on Thrombosis and Haemostasis.