Clinical impact of enhanced inhibition of P2Y12-mediated platelet aggregation in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention

The combination of aspirin and clopidogrel at a loading dose of 300 mg followed by a maintenance dose of 75 mg daily is a well-established antiplatelet therapy for the secondary prevention of thrombotic complications in the settings of acute coronary syndrome and/or percutaneous coronary intervention (PCI). Despite the demonstrated clinical benefits associated with this antiplatelet therapy, there is accumulating evidence that a consistent proportion of patients persist in having high levels of platelet aggregation following standard clopidogrel dose. Importantly, the high platelet reactivity after clopidogrel treatment has been associated with higher risk for cardiovascular ischemic events, including stent thrombosis. This has warranted the need for alternative oral antiplatelet regimens that achieve a higher degree of platelet inhibition. Several functional studies have shown that a higher clopidogrel loading dose (600 mg) compared with standard dose, and novel oral adenosine diphosphate platelet receptor (P2Y12) antagonists compared with clopidogrel achieve a faster onset of action, increased platelet inhibition, and a more predictable drug response. These more favorable pharmacodynamic characteristics are of particular interest in the setting of primary PCI for ST-segment elevation myocardial infarction (STEMI), in which rapid and consistent inhibition of platelet activation and aggregation is desirable for therapeutic success. The present article reviews data on the clinical impact of enhanced P2Y12 inhibition with either higher clopidogrel dosing or new oral antiplatelet agents, including prasugrel and ticagrelor, in the setting of STEMI, focusing on results in the setting of primary PCI.