ADP-induced platelet aggregation frequently fails to detect impaired clopidogrel-responsiveness in patients with coronary artery disease compared to a P2Y12-specific assay.
Incomplete P2Y(12)-inhibition during clopidogrel treatment is associated with increased cardiovascular events and mortality after coronary intervention. We investigated the incidence of impaired individual clopidogrel-responsiveness using a P2Y(12)-specific and pre-treatment-independent assay in a real world situation. One hundred consecutive patients with coronary artery disease (CAD) on combined acetylsalicylic acid and clopidogrel treatment (75 mg/d) and 33 patients on aspirin only were screened for platelet ADP-induced signalling by conventional aggregometry, platelet P-selectin expression and the platelet reactivity index (PRI). Impaired P2Y(12)-specific inhibition by clopidogrel was defined as a PRI>50%. Functional platelet reactivity was significantly lower in clopidogrel-treated patients compared to controls. Impaired individual response to treatment was diagnosed in 69% of clopidogrel-treated patients. Conventional assessment of maximum ADP-induced platelet aggregation failed to detect impaired P2Y(12) inhibition in 36% of patients identified by PRI to have an impaired clopidogrel response. Impaired clopidogrel response was associated with lower HDL levels and a history of hyperlipidaemia. In conclusion, PRI as a P2Y(12)-specific assay to evaluate the treatment effect of clopidogrel in patients with CAD revealed insufficient P2Y(12)-inhibition in two thirds of patients in a real-world scenario indicating a markedly higher incidence than previously assumed. PRI detected significantly more patients with impaired response than conventional platelet aggregation.
Schäfer
Andreas
A
Medizinische Klinik und Poliklinik I, Universitätsklinikum Würzburg, Josef-Schneider-Strasse 2, Würzburg, Germany. a.schaefer@medizin.uni-wuerzburg.de
Weinberger
Sarah
S
Flierl
Ulrike
U
Eigenthaler
Martin
M
Störk
Stefan
S
Walter
Ulrich
U
Ertl
Georg
G
Bauersachs
Johann
J
D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D000077144:Clopidogrel; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D004351:Drug Resistance; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D015994:Incidence; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058925:Receptors, Purinergic P2Y12; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D019007:P-Selectin; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin