mised 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 control (5.8% vs. 8.6%; p=0.043). In addition, there was a strong trend toward a significant decrease in mortality with Aggrastat with respect to all-cause death (2.2% in the Aggrastat arm vs. 4.1% in the control arm; p=0.051). This mortality benefit was mainly due to a reduction of cardiac death (2.1% vs. 3.6%; p=0.086). At 1-year follow-up (the secondary endpoint), the mortality difference was maintained (3.7% vs. 5.8%; p=0.078 for all-cause mortality and 2.5% vs. 4.4% for cardiac mortality; p=0.061).
Patients who underwent primary PCI (86% of study population of pooled analysis) demonstrated a significant reduction in mortality both at 30 days (1.0% in the Aggrastat group vs. 3.9% in the control group; p=0.001) and at 1 year (2.4% for Aggrastat vs. 5.5% for control; p=0.007).
MULTISTRATEGY study
The MULTISTRATEGY study was an open-label, 2X2 factorial, multinational trial which compared the Aggrastat (n=372) with abciximab (n=372) when used in conjunction with either a sirolimus-eluting (SES) or bare metal stent (BMS), in patients with STEMI.
