title: Validation of a P2Y12-receptor specific whole blood platelet aggregation assay.
abstract: Testing of P2Y12-receptor antagonist effects can support clinical decision-making. However, most platelet function assays use only ADP as agonist which is not P2Y12-receptor specific. For this reason P2Y12-receptor specific assays have been developed by adding prostaglandin E1 (PGE1) to reduce ADP-induced platelet activation via the P2Y1-receptor. The present study sought to evaluate a P2Y12-receptor specific assay for determination of pharmacodynamic and clinical outcomes. This study enrolled 400 patients undergoing coronary stenting after loading with clopidogrel or prasugrel. ADP-induced platelet reactivity was assessed by whole blood aggregometry at multiple time points with a standard ADP assay (ADPtest) and a P2Y12-receptor specific assay (ADPtest HS, both run on Multiplate Analyzer, Roche Diagnostics). Patients were clinically followed for 1 month and all events adjudicated by an independent committee. In total, 2084 pairs of test results of ADPtest and ADPtest HS were available showing a strong correlation between results of both assays (r = 0.96, p < 0.001). These findings prevailed in multiple prespecified subgroups (e.g., age; body mass index; diabetes). Calculated cutoffs for ADPtest HS and the established cutoffs of ADPtest showed a substantial agreement for prediction of ischemic and hemorrhagic events with a Cohen's κ of 0.66 and 0.66, respectively. The P2Y12-receptor specific ADPtest HS assay appears similarly predictive for pharmacodynamic and clinical outcomes as compared to the established ADPtest assay indicating its applicability for clinical use. Further evaluation in large cohorts is needed to determine if P2Y12-receptor specific testing offers any advantage for prediction of clinical outcome.
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Amann
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Miroslaw
authors.initials: M
authors.lastname: Ferenc
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Christian M
authors.initials: CM
authors.lastname: Valina
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Bömicke
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Stratz
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Leggewie
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.affiliation: a Department of Cardiology and Angiology II , University Heart Center Freiburg-Bad Krozingen , Bad Krozingen , Germany.
authors.forename: Willibald
authors.initials: W
authors.lastname: Hochholzer
mesh_terms: D000368:Aged; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000379:methods; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010979:Platelet Function Tests / Q000379:methods / Q000592:standards; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058925:Receptors, Purinergic P2Y12 / Q000378:metabolism*; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12
keywords: Clopidogrel; platelet reactivity; prasugrel; prostaglandin E1