Randomized Comparison of Prasugrel (CS-747, LY640315), a Novel Thienopyridine P2Y 12 Antagonist, With Clopidogrel in Percutaneous Coronary Intervention Results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)–TIMI 26 Trial Coronary Heart Disease

Background —Despite the current standard antiplatelet regimen of aspirin and clopidogrel (with or without glycoprotein IIb/IIIa inhibitors) in percutaneous coronary intervention patients, periprocedural and postprocedural ischemic events continue to occur. Prasugrel (CS-747, LY640315), a novel potent thienopyridine P2Y 12 receptor antagonist, has the potential to achieve higher levels of inhibition of ADP-induced platelet aggregation than currently approved doses of clopidogrel. Methods and Results —Joint Utilization of Medications to Block Platelets Optimally–Thrombolysis In Myocardial Infarction 26 (JUMBO-TIMI 26) was a phase 2, randomized, dose-ranging, double-blind safety trial of prasugrel versus clopidogrel in 904 patients undergoing elective or urgent percutaneous coronary intervention. Patients were randomized to either standard dosing with clopidogrel or 1 of 3 prasugrel regimens. Subjects were monitored for 30 days for bleeding and clinical events. The primary end point of the trial was clinically significant (TIMI major plus minor) non–CABG-related bleeding events in prasugrel- versus clopidogrel-treated patients. Hemorrhagic complications were infrequent, with no significant difference between patients treated with prasugrel or clopidogrel in the rate of significant bleeding (1.7% versus 1.2%; hazard ratio, 1.42; 95% CI, 0.40, 5.08). In prasugrel-treated patients, there were numerically lower incidences of the primary efficacy composite end point (30-day major adverse cardiac events) and of the secondary end points myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis. Conclusions —In this phase 2 study, which was designed to assess safety when administered at the time of percutaneous coronary intervention, prasugrel and clopidogrel both resulted in low rates of bleeding. The results of this trial serve as a foundation for the large phase 3 clinical trial designed to assess both efficacy and safety. ( Circulation . 2005;111:3366-3373.) ANOVA as appropriate. Major prespecified analyses included all prasugrel dosing groups combined versus clopidogrel and each prasugrel dosing group individually compared with clopidogrel. A sample size of 900 subjects was chosen to provide at least 80% power to detect a 2.5-fold increase in the risk of significant non–CABG-associated bleeding that was estimated from previous studies to occur in 5% to 7.5% of clopidogrel patients. 10,31 Secondary end points should be considered exploratory because the trial was not designed or powered to formally test these end points. Primary analyses were performed by an independent statistician at the contract research organization (Parexel, International) and verified by the sponsor and the TIMI Study Group independently. The TIMI Study Group had possession of and full access to all databases used for the analysis of the trial.