|Pub Date:||Friday, August 19, 2005|
|Authors:||Morton J. Kern, MD|
|Article:||Randomized Comparison of Prasugrel (CS-747, LY640315), a Novel Thienopyridine P2Y12 Antagonist, with Clopidogrel in Percutaneous Coronary Intervention: Results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)TIMI 26 Trial|
- Wiviott SD; Antman EM; Winters KJ; Weerakkody G; Murphy SA; Behounek BD; Carney RJ; Lazzam C; McKay RG; McCabe CH; Braunwald E; JUMBO-TIMI 26 Investigators, Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial, Circulation, 111 (25) 3366-73. View in PubMed
This study addressed the question of whether a novel new thienopyridine P2Y12 receptor antagonist could inhibit platelets to the same degree as a currently employed standard clopidogrel regimen with an equal efficacy of bleeding outcomes.
In the JUMBO 26 trial, a phase II randomized dose-ranging study in 1904 patients undergoing elective or urgent percutaneous coronary intervention (PCI), patients were randomized between clopidogrel (300-mg load with 75 mg/day for 6 months) versus one of three regimens of prasugrel, (1) a loading dose of 40 mg with daily dose of 7.5 mg, (2) a loading dose of 60 mg with 10 mg daily, and (3) 60 mg load and 15 mg daily. Each of these study arms had at least 200 patients. The primary end point of the trial was non–coronary artery bypass graft (CABG)-related bleeding. The findings indicated that hemorrhagic complications were infrequent with no differences between the groups, and prasugrel-treated patients had, numerically, slightly lower incidents of primary composite end points at 30 days and of secondary end points—myocardial infarction, recurrent ischemia, and clinical target vessel thrombosis—at 30 days.
This dose-ranging prospective study established the safety and efficacy of low bleeding rates with the new P2Y12 antagonist compared to clopidogrel and will serve as the basis for a larger multicenter trial of major long-term clinical outcomes.
Better antiplatelet regimens for PCI would address several post-PCI problems, namely, the potential need of surgery within the few days after receipt of the drugs and the variability and resistance that have been reported with currently used clopidogrel dosing regimens. Prasugrel, a new thienopyridine agent for adenosine diphosphate (ADP)-induced receptor antagonism, appears to be more potent than clopidogrel and is associated with less resistance to platelet inhibition. Although the current study demonstrated the efficacy of this new agent without excess bleeding, it was not designed to test clinical efficacy longer than 6 months. The statistical power to determine whether the 300-mg loading dose of clopidogrel and the pretreatment regimen were satisfactory can be questioned. The design of the JUMBO-TIMI 26 trial did not allow for a comparison to high-dose clopidogrel (600 mg or longer duration of study pretreatment). Given the difficulties and problems related to the routine use of clopidogrel in some individuals, this novel P2Y12 antagonist is a welcome addition, provided that future trials, specifically that of TIMI 38 (a trial to assess improvement in therapeutic options by optimizing platelet inhibition with prasugrel) demonstrate continued efficacy without excess bleeding or subacute thrombosis.
-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association. --