Hign on treatment platelet reactivity by more than one agonist predicts 12-month follow-up cardiovascular death and non-fatal myocardial infarction in acute coronary syndrome patients receiving coronary stenting

Abstract There is some data available on the role of high on-treatment platelet reactivity by ADP whereas, as regards arachidonic acid or other agonists, there is no proof of the best cut-off for identifying populations with a different cardiovascular outcome by the construction of appropriate receiver-operator characteristics (ROC) curves. We enrolled 1,108 acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) with stent implantation and followed them up for 12 months. Platelet reactivity was assessed by light transmission aggregometry (LTA) using 10 microM ADP, 1 mM arachidonic acid (AA) and 2 microg/ml collagen. At a 12-month follow-up, we found 37 cardiovascular deaths (3.3%), 54 non-fatal myocardial infarctions (MI) (4.8%) and 154 target vessel revascularisations (TVR) (13.8%). ROC analysis demonstrated that 10 microM ADP LTA, 1 mM AA and 2 microg/ml collagen LTA were able to distinguish between patients with and without subsequent cardiovascular death and non-fatal MI (area under the curve for 10 microM ADP 0.63 (0.55-0.71), p<0.001; for 1 mM AA 0.68 (0.61-0.76), p<0.0001; for 2 microg/ml collagen 0.62 (0.52-0.73), p<0.0111), whereas no association was demonstrated with the occurrence of TVR. Ten microM ADP LTA>or=55%, 1 mM AA LTA>or=15% and 2 microg/ml collagen LTA>or=31% were identified as the optimal cut-off to predict cardiovascular death and non-fatal MI at 12-month follow-up. The contemporary platelet hyperreactivity to more than one agonist was associated with a higher risk of 12-month cardiovascular death and MI, whereas isolated platelet hyperreactivity to only one agonist had not a predictive value [10 microM ADP LTA>or=55% + 1 mM AA LTA>or=15%: odds ratio [OR]=3.6(2.4-6.1), p<0.0001; ADP LTA>or=55% + 1 mM AA LTA>or=15% + 2 microg/ml collagen LTA>or=31%: OR=4.7(2.9-7.7), p<0.0001]. In this prospective study on a large number of acute coronary syndrome patients undergoing stent implantation, we have found that high on-treatment platelet reactivity measured by LTA induced by more than one agonist--AA, ADP, collagen--is an independent risk factor for 12-month cardiovascular death and non-fatal MI. Isolated platelet hyperreactivity to only one agonist has not a predictive value for clinical recurrences.