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Prasugrel for the treatment of patients with acute coronary syndrome

Author(s): Filippo Marzot | Vittorio Pengo

Journal: Vascular Health and Risk Management
ISSN 1176-6344

Volume: 2009;
Issue: default;
Start page: 321;
Date: 2009;
Original page

Filippo Marzot, Vittorio PengoClinical Cardiology, Thrombosis Centre, University of Padua, ItalyAbstract: Prasugrel (CS-747, LY640315) is a novel member of the thienopyridine class of oral anti-platelet agents (also including ticlopidine and clopidogrel). Like other thienopyridines, prasugrel is a prodrug that is inactive in vitro. Prasugrel’s conversion to its active metabolite is more rapid and efficient than that of other thienopyridines, with a less strict dependence on specific cytochrome P-450 enzymes. Prasugrel’s active metabolite (R-138727) binds specifically and irreversibly to the platelet P2Y12 purinergic receptor, thus inhibiting ADP-mediated platelet activation and aggregation. Preclinical data and early clinical data in healthy subjects showed greater platelet inhibition and consistency with prasugrel as opposed to clopidogrel. Clinical studies in patients with cardiovascular disease confirmed the greater efficacy of prasugrel compared with clopidogrel. Collectively, these phase 1/1b studies and a phase 2 study (JUMBO-TIMI 26) aided in dose selection for the phase 3 trial (TRITONTIMI 38) in patients with acute coronary syndrome undergoing percutaneous coronary intervention. This trial once again confirmed the greater anti-platelet effect of prasugrel, but also highlighted a higher risk of bleeding, even fatal. Another phase 2 trial (PRINCIPLE-TIMI 44) compared prasugrel and high-dose clopidogrel in patients undergoing cardiac catheterization for planned PCI.Keywords: prasugrel, oral antiplatelet agents, acute coronary syndrome