Landmark analysis of the TRITON-TIMI 38 trial demonstrates significant benefit with the loading and maintenance doses of prasugrel

May 20, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

Boston, MA: The latest analysis of the TRITON-TIMI 38 trial demonstrates that both the loading and the maintenance doses of prasugrel are superior to clopidogrel in reducing ischemic events.

Previous publications from the TRITON-TIMI 38 trial demonstrate that prasugrel is superior to clopidogrel in terms of reduction in ischemic events and stent thrombosis compared with clopidogrel at the expense of TIMI major bleed including fatal bleed.

In the latest issue of JACC, the TIMI trial investigators performed an analysis to assess the impact of the loading (60 mg) and maintenance doses (10 mg) of prasugrel over a range of individual pre-specified efficacy end points.

A landmark analysis for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial. This analysis demonstrated that there was a significant reduction in myocardial infarction (HR 0.81, 95% CI 0.7 to 0.95, p=0.008 and HR 0.69, 95% CI 0.58 to 0.83, p<0.0001), stent thrombosis (HR 0.49, 95% CI 0.29 to 0.82, p=0.006 and HR 0.45, 95% CI 0.32 to 0.64, p<0.0001), and urgent target vessel revascularization (HR 0.66, 95% CI 0.43 to 0.99, p=0.047 and HR 0.65, 95% CI 0.52 to 0.82, p=0.0003) during the first 3 days after randomization and from 3 days to the end of the study with prasugrel compared with clopidogrel.

While the net clinical benefit (death from any cause, nonfatal myocardial infarction, nonfatal stroke and nonfatal TIMI major non-CABG-related bleed) occurred in the loading (HR 0.85, 95% CI 0.74 to 0.98, p=0.025) and the maintenance phase (HR 0.87, 95% CI 0.77 to 0.98, p=0.028), major bleed seem to occur in the maintenance phase rather than the loading phase [HR 1.39, 95% CI 1.02 to 1.89, p=0.036 vs. HR 1.22 95% CI 0.81 to 1.84, p=0.35].

This study demonstrates that the benefits of prasugrel over clopidogrel occurred early as well as in the maintenance phase in terms of reductions in ischemic events. The authors recommend using a reduced maintenance dose (5 mg) among high risk population such as the elderly and those with low body weight due to the association of increased bleeding events in the maintenance phase of prasugrel therapy.

Source

 * 1) http://content.onlinejacc.org/cgi/content/short/51/21/2028