The primary endpoint was a composite of death, nonfatal MI, urgent target vessel revascularization (uTVR), or thrombotic bailout GP IIb/IIIa inhibitor therapy within a median follow-up of 180 days after the index procedure. The safety endpoints of major and minor bleeding were defined according to the TIMI criteria.

In the intent-to-treat population, the cumulative incidence of the primary end point was 35% and 20% in placebo and Aggrastat groups, respectively (hazard ratio [HR] 0.51 [95% confidence interval (CI), 0.29 to 0.88]; p=0.01). As compared with placebo, there was a significant reduction in the composite of death, MI, or uTVR in the Aggrastat group (31% vs. 20%, HR, 0.57 95% CI, 0.99–0.33]; p=0.048.
EVEREST study

The randomised open-label EVEREST trial compared the upstream 0.4 microgram/kg/min loading dose regimen initiated in the coronary care unit with the Aggrastat 25 microgram/kg dose bolus regimen or abciximab 0.25 milligram/kg initiated 10 minutes prior to PCI. All patients additionally received ASA and a thienopyridine. The 93 enrolled NSTE-ACS patients underwent angiography and PCI as appropriate, within 24-48 hours of admission.

With respect to the primary endpoints of tissue level perfusion and troponin I release, the results of EVEREST determined significantly lower rates of post-PCI TMPG 0/1 (6.2% vs. 20% vs. 35.5%, respectively; p=0.015), and improved post-PCI MCE score index (0.88 ± 0.18 vs. 0.77 ± 0.32 vs. 0.71 ± 0.30, respectively; p<0.05).

The incidence of post-procedural cardiac Troponin I (cTnI) elevation was significantly reduced in patients treated with the upstream Aggrastat regimen compared with PCI 25 microgram/kg dose bolus Aggrastat or abciximab (9.4% vs. 30% vs. 38.7%, respectively; p=0.018). The cTnI levels post-PCI were also significantly decreased with the upstream regimen of Aggrastat compared with PCI Aggrastat (3.8 ± 4.1 vs. 7.2 ± 12; p=0.015) and abciximab (3.8 ± 4.1 vs. 9 ± 13.8; p=0.0002). The comparison between the PCI Aggrastat 25 microgram/kg dose bolus and abciximab regimens indicated no significant differences in the rate of TMPG 0/1 post-PCI (20% vs. 35%; p=NS).

On-TIME 2 study

The On-TIME 2 trial was a multi-centre, prospective, randomised, controlled clinical trial which was designed to assess the effect of early upfront Aggrastat administration using the 25 microgram/kg dose bolus regimen in patients with STEMI planned for primary PCI. All patients received ASA, a 600 mg loading dose of clopidogrel, and unfractionated heparin. The use of bail-out Aggrastat was allowed according to pre-specified criteria. The study was accomplished in two phases: a pilot, open label phase (n=414) followed by a larger double-blind phase (n=984). A pooled analysis of data from both phases was pre-specified to eva luate the effect of the 25 microgram/kg dose bolus regimen compared to control as measured by a primary endpoint defined as the 30-day MACE rate (death, recurrent MI and uTVR).

In this pooled analysis, MACE at 30 days was significantly reduced by early upfront initiation of Aggrastat compared to