Abstract 3803: Platelet Inhibition with Prasugrel (CS-747) versus Clopidogrel in Patients Undergoing Coronary Stenting: The Subset From the JUMBO Trial
Background: Based on the animal, and Phase 1 studies prasugrel, an experimental platelet ADP P2Y12 receptor blocker, may be more potent platelet inhibitor than clopidogrel. We thought to compare the antiplatelet properties of prasugrel and clopidogrel in the subset from the Phase 2 randomized JUMBO trial.
Methods: Patients undergoing coronary stenting were randomized to one of three arms of prasugrel (40mg loading, and 7.5mg maintenance; 60/10mg, ; or 60/15mg), or clopidogrel (300/75mg). Aspirin and GP IIb/IIIa inhibitors were allowed. Platelet activity was assessed at baseline, at 4, and 24 hours, and at 30 days after stent implantation in substudy particiants, and 124 historic clopidogrel controls.
Results: Independently of the loading, or maintenance dose, patients treated with prasugrel exhibited significantly more potent platelet inhibition as determined by ADP-, and collagen-induced aggregation, Ultegra“ Analyzer, and surface expression of PECAM-1, GPIIb/IIIa antigen, and activity with PAC-1 antibody, GPIb, P-selectin, CD40-ligand, GP37, and thrombosdondin receptor when compared with those treated with clopidogrel. There were no differences between antiplatelet agents with regard to vitronectin, LAMP-1, LAMP-3, PAR-1 (intact and cleaved epitopes) thrombin receptor expression, or formation of platelet-monocyte microparticles. Two patients treated with prasugrel 10 mg/daily exhibited complete inhibition of collagen-induced aggregation at 30 days.
Conclusion: At the dosing regimens chosen in the JUMBO trial, prasugrel is unquestionably more potent antiplatelet agent than clopidogrel. Two episodes of profound platelet inhibition which are not observed with clopidogrel raise the possibility of higher bleeding risks especially during chronic prasugrel use. Whether stronger platelet inhibition will yield better clinical outcomes and/or increased bleeding especially in the outpatient setting remain to be determined in the ongoing head-to-head Phase 3 superiority TRITON trial.