High on-aspirin platelet reactivity as measured with aggregation-based, cyclooxygenase-1 inhibition sensitive platelet function tests is associated with the occurrence of atherothrombotic events

Background: High on-aspirin platelet reactivity (HAPR) is associated with atherothrombotic events following percutaneous coronary intervention (PCI). The aim of the present study was to identify the platelet function test sensitive for platelet cyclooxygenase-1 inhibition that best predicts atherothrombotic events. Methods and results: Nine hundred and fifty-one consecutive patients on dual antiplatelet therapy undergoing elective PCI were enrolled. On-aspirin platelet reactivity was measured in parallel by arachidonic acid (AA)-induced light transmittance aggregometry (AA-induced LTA), the VerifyNow (R) Aspirin Assay (VerifyNow (R) Aspirin Assay), the arachidonic acid prestimulated IMPACT-R (IMPACT-R AA) and the PFA-100 collagen/epinephrine cartridge (PFA COL/EPI). Cut-offs for HAPR were established by receiver-operator characteristic curve analysis. At 1-year follow-up, the composite of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischemic stroke occurred more frequently in patients with HAPR when assessed by LTA [10.1% vs. 6.0%, P = 0.020 (n = 925)] and VerifyNow (R) [13.3% vs. 5.9%, P = 0.015 (n = 422)]. The VerifyNow (R) ASA assay (AUC = 0.78) and, to a lesser extent, AA-induced LTA (AUC = 0.73) added significantly to a model consisting of clinical and procedural risk factors in predicting atherothrombotic events. In contrast, the IMPACT-R (n = 791) and the PFA Collagen/Epinephrine (n = 719) were unable to discriminate between patients with and without primary endpoint at 1-year follow-up. None of the platelet function tests was able to identify patients at risk for bleeding. Conclusions: AA-induced LTA and the VerifyNow (R) ASA test were able to identify aspirin-treated patients undergoing PCI with stenting at risk for atherothrombotic events. The VerifyNow (R) Aspirin Assay had the highest predictive accuracy. None of the tests was able to identify patients at higher risk of bleeding.