TRITON-TIMI: Prasugrel is safe, effective despite bleeding risks

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The TRITON-TIMI trial, which compared prasugrel (Effient) to clopidogrel (Plavix) as a dual anti-platelet therapy, established that the benefit of using prasugrel in a dual anti-platelet therapy, despite its bleeding complications, according to Deepak Bhatt, MD, associate director of the Cardiovascular Coordinating Center at the Cleveland Clinic.

Bhatt provided the independent evaluation of the results of the TRITON-TIMI trial at the Cardiovascular Revascularization Therapies (CRT) 2008 meeting in Washington, D.C., last week.

The TRITON–TIMI 38 study design evaluated patients with acute coronary syndrome (STEMI or UA/NSTEMI) and planned percutaneous coronary intervention (PCI) with dual anti-platelet therapy. The 13,000 participants took aspirin and were double-blinded to take either prasugrel or clopidogrel with a median duration of 14.5 months.

The primary endpoint is cardiovascular (CV) death, MI and stroke, and the secondary endpoint was CV death, MI, stroke, re-ischemia CV death, MI and urgent target vessel revascularization.

The primary endpoint was higher with clopidogrel (12.1%) than with prasugrel (9.9%). However, prasugrel produced higher bleeding events (2.4% vs. 1.8%). The net clinical benefit of death, MI, stroke and major bleed (non CABG) also favors prasugrel: 13.9% for clopidogrel, and 12.2% for prasugrel.

In the diabetic subgroup of 3,146 patients, prasugrel demonstrated 30% reduction of CV death, MI and stroke to clopidogrel (17% vs. 12.2%). Moreover, prasugrel reduced the risk of in-stent thrombosis by 48% over clopidogrel.  

The two arms of the Phase III of the CHAMPION program are currently underway, and the primary endpoint is superiority for ischemic events.
•    First arm: Prasugrel vs. clopidogrel 600 mg at the start of PCI in 9,000 patients.
•    Second arm: Prasugrel vs. clopidogrel 600 mg at the end of PCI in 6,300 patients.

In another ongoing trial, OASIS 7 has enrolled about 14,000 patients with UA/NSTEMI planned for early invasive strategy, for intended use of PCI as early as possible within 24 hours.

Finally, Bhatt highlighted the TRILOGY-ACS, which has two arms: one of which will assess the treatment decision for medical management determined < 24 hours and the other, the treatment decision determined > 24 hours, or chronic clopidogrel therapy.

The TRILOGY-ACS, being conducted at Duke Clinical Research Institute in Durham, N.C., will have a median duration of treatment of approximately 18 months.
In a carefully defined ACS population with a plan for PCI, prasugrel was superior to clopidogrel. Bhatt advised for medical therapy to await the results of the TRILOGY-ACS trial.

He concluded that prasugrel presents a benefit in reducing MI, DES thrombosis and BMS thrombosis, and while an increase in serious bleeding occurs, there is still a net clinical benefit in the majority of the population studied.