Antiplatelet Therapy in ACS Patients: Comparing Appropriate P2Y12 Inhibition by Clopidogrel to the Use of New P2Y12 Inhibitors

Aim: In percutaneous coronary intervention (PCI)-treated acute coronary syndrome (ACS) patients on clopidogrel therapy, high on-treatment platelet adenosine diphosphate (ADP) reactivity was observed in numerous studies, with significant increases in non-fatal myocardial infarction, definite/probable stent thrombosis, or cardiovascular mortality. Compared to clopidogrel, prasugrel and ticagrelor provide more potent platelet inhibition. Whether new P2Y12 inhibitors reduce thrombotic events in a similar manner compared to the rate observed with appropriate P2Y12 inhibition by clopidogrel must still be determined. This study sought to compare longterm outcomes between clopidogrel responders (platelet reactivity index [PRI] vasodilator-stimulated phosphoprotein [VASP] < 61%) and patients under prasugrel or ticagrelor therapy following PCI-treated ACS. Methods: 730 ACS patients undergoing urgent PCI were prospectively enrolled into two groups: clopidogrel responders (n = 448) and those under ticagrelor or prasugrel therapy (n = 282). The primary endpoint was a composite of cardiovascular death, myocardial infarction, stent thrombosis, and stroke; the secondary endpoint comprised major hemorrhagic events. Results: The median follow-up was 260 ± 186 days. Clopidogrel patients were older and more likely to present non-ST segment elevation myocardial infarction, cardiovascular risk factors, atrial fibrillation, or prior vascular disease. After propensity score matching, the primary endpoint was met in 7.1% of the clopidogrel group and 4.1% of the prasugrel/ticagrelor group (p = 0.43). Minor bleeding events were significantly reduced in the clopidogrel group (1.1% vs. 3%; p = 0.03). In a multivariate analysis, the antiplatelet treatment strategy was not an independent primary endpoint predictor. Conclusion: In PCI-treated ACS patients, clopidogrel therapy and PRI VASP < 61% were not associated with increased risks of thrombotic events compared to prasugrel or ticagrelor therapy.