Variable responsiveness to clopidogrel and aspirin among patients with acute coronary syndrome as assessed by platelet function tests

Abstract 

Unresponsiveness to clopidogrel or aspirin has been reported in patients with acute coronary syndrome (ACS). Platelet aggregometry (PA) and the Impact-R [Cone and Plate(let) Analyzer (CPA) technology, measuring whole blood platelet adhesion under flow conditions] were compared in detecting laboratory unresponsiveness to clopidogrel and aspirin among ACS patients.

Platelet-rich plasma (PRP) samples were evaluated in 404 patients by PA using adenosine diphosphate (ADP) and arachidonic acid (AA) and whole blood samples by the Impact-R ADP- and AA-response tests. The first cohort (n=114) was assayed by PA on days 1 and 4 of the onset of ACS. A patient with relative decrease of ≤10% in ADP-induced maximal platelet aggregation after clopidogrel treatment was defined as laboratory non-responding (NR) patient to clopidogrel. This relative value correlated well with an absolute value of ADP-induced aggregation ≥70%. A patient with an absolute value of AA-induced maximal aggregation ≥60% was defined as laboratory NR patient to aspirin. The second cohort (n=290) was tested on day 4 by both systems and results analyzed by receiver operating characteristic curve. The following cut-off values of the Impact-R surface coverage were obtained: ≤2.8% and ≤3.4% for clopidogrel and aspirin NR patients, respectively. The incidence of NR patients to clopidogrel and aspirin, according to the two methods was 27% and 22%, respectively.

Impact-R compared to PA in detecting clopidogrel and aspirin NR patients revealed: 79% and 82% agreement, 71% and 73% sensitivity, 83% and 86% specificity, respectively. In conclusion, the Impact-R and PA results demonstrated high degree of similarity.

Abbreviations:: ACS, acute coronary syndrome, PA, platelet aggregometry, CPA, Cone and Plate(let) Analyzer, PRP, platelet-rich plasma, ADP, adenosine diphosphate, AA, arachidonic acid, NR, non-responding, ROC, receiver operating characteristic, SC, surface coverage, PCI, percutaneous coronary intervention, VASP, vasodilator-stimulated phosphoprotein, PPP, platelet-poor plasma, PBS, phosphate-buffered saline, AUC, area under the curve, SD., standard deviation

Keywords: Acute coronary syndrome, Platelets, Clopidogrel, Aspirin, Platelet aggregometer, Impact-R