Key result
Prasugrel improves clinical efficacy over clopidogrel in ACS but increases bleeding risk.
Why the study?
Does prasugrel improve clinical efficacy compared to clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention?
Does prasugrel improve clinical efficacy compared to clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention?
Prasugrel is a potent thienopyridine that offers greater platelet inhibition and clinical efficacy than clopidogrel in ACS patients undergoing PCI, though at the cost of increased bleeding risk.
May guide P2Y12 selection in ACS despite bleeding risk; leaves open optimal use in contemporary cohorts.
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 (TRITON-TIMI 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.
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A 2009 study conducted a review in Acute coronary syndrome. Prasugrel vs. Clopidogrel was evaluated. Prasugrel demonstrated greater anti-platelet effect and clinical efficacy compared with clopidogrel in patients with acute coronary syndrome, but was associated with a higher risk of bleeding.
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