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Detecting a thienopyridine effect by platelet reactivity assessment and its implications for risk stratification
Author(s) -
Price M. J.,
Baker B. A.,
Jakubowski J. A.,
Li W.,
Heiselman D. E.,
Angiolillo D. J.
Publication year - 2014
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/jth.12505
Subject(s) - thienopyridine , prasugrel , clopidogrel , p2y12 , medicine , aspirin , ticagrelor , platelet , cardiology , anesthesia
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.