Prasugrel for the treatment of patients with acute coronary syndrome.
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.
Marzot
Filippo
F
Clinical Cardiology, Thrombosis Centre, University of Padua, Padova, Italy.
Pengo
Vittorio
V
D054058:Acute Coronary Syndrome / Q000188:drug therapy / Q000628:therapy*; D000284:Administration, Oral; D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D002986:Clinical Trials as Topic; D000077144:Clopidogrel; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068799:Prasugrel Hydrochloride; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013876:Thiophenes; D000077144:Clopidogrel; D000068799:Prasugrel Hydrochloride; D013988:Ticlopidine