Supplement articleCharacteristics of new P2Y12 inhibitors: selection of P2Y12 inhibitors in clinical practiceGolino, PaoloAuthor Information Cattedra di Cardiologia, Seconda Università di Napoli, UOC di Cardiologia a Direzione Universitaria, A.O. Sant’Anna e San Sebastiano – Caserta, Italy Correspondence to Prof. Paolo Golino, Department of Cardio-Thoracic and Respiratory Sciences, Second University of Naples, via Leonardo Bianchi, 1, 80131 Naples, Italy Tel: +39 0823 306395; fax: +39 0823 232395; e-mail: [email protected] Received 18 June, 2013 Accepted 26 June, 2013 Journal of Cardiovascular Medicine: December 2013 - Volume 14 - Issue - p S22-S30 doi: 10.2459/JCM.0b013e328364bb18 Buy Metrics Abstract The options for antithrombotic therapy have recently been expanded, facilitating optimal tailored treatment. Dual antiplatelet therapy with aspirin and an approved adenosine diphosphate P2Y12 receptor antagonist is recommended for the management of patients with acute coronary syndromes (ACS). However, there are a number of controversies: which P2Y12 inhibitor to choose; how long should antiplatelet therapy be used so as to prevent thrombotic events and minimize bleeding risks; whether to use drug-eluting (DES) or bare-metal stents (BMS) and how to manage the individual variability in response to clopidogrel. Clopidogrel in combination with aspirin has been the standard dual antiplatelet regimen for ACS. The new, more potent P2Y12 inhibitors, prasugrel and ticagrelor, have shown improved antithrombotic effects compared with clopidogrel in patients with ACS (with or without ST-segment elevation myocardial infarction) in landmark trials, even if they were associated with an increased risk of major bleeding. Different pharmacogenetic and pharmacodynamic characteristics may explain, in part, the different pharmacologic and clinical responses to these antiplatelet agents. Importantly, both clopidogrel and prasugrel are prodrugs, i.e., they need to be converted in vivo into active metabolites that selectively and irreversibly bind the P2Y12 receptor. Unlike clopidogrel, however, common functional cytochrome P450 genetic variants do not affect prasugrel active metabolite levels or inhibition of platelet aggregation. In contrast, ticagrelor is not a prodrug (i.e., does not require hepatic metabolism to exert its antiplatelet effect) and represents the first oral P2Y12 receptor antagonist that is reversibly bound. Similar to prasugrel, ticagrelor achieves greater and more rapid inhibition of platelet function than clopidogrel. Evidence suggests that the new P2Y12 antagonists may offer improved antithrombotic effects compared with clopidogrel in selected patients for the optimal management of ACS in clinical practice. © 2013 Italian Federation of Cardiology. All rights reserved.