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. Either Aggrastat (bolus of 25 microgram/kg, followed by an infusion at 0.15 microgram/kg/min continued for 18 to 24 hours) or abciximab (bolus of 0.25 mg/kg, followed by a 12-hour infusion at 0.125 microgram/kg/min) was initiated before arterial sheath insertion during the angiography. All patients received unfractionated heparin, ASA and clopidogrel.
The primary endpoint for the drug comparison was cumulative ST-segment resolution expressed as the proportion of patients who achieve at least 50% recovery within 90 minutes after the last balloon inflation and tested the hypothesis that Aggrastat is noninferior to abciximab with respect to this endpoint.
In the intention-to-treat population, the percentage of patients with at least 50% recovery from ST-segment elevation was not significantly different between Aggrastat (85.3%) and abciximab (83.6%), demonstrating the non-inferiority of Aggrastat to abciximab (RR for Aggrastat vs. abciximab, 1.020; 97.5% CI, 0.958-1.086; p<0.001 for non-inferiority).
At 30 days, the rates of major adverse cardiac events (MACE) were similar for abciximab and Aggrastat (4.3% vs. 4.0%, respectively; p=0.85) with these results maintained at 8 months (12.4% vs. 9.9%, respectively; p=0.30).
In On-TIME 2 and MULTISTRATEGY, patients were treated with dual oral antiplatelet therapy consisting of ASA and high-dose clopidogrel. The efficacy of Aggrastat in combination with either prasugrel or ticagrelor has not been established in randomised controlled trials.
Meta-analysis of Randomised Trials of Aggrastat 25 microgram/kg Dose Bolus Regimen
The results of a meta-analysis eva luating the efficacy of the Aggrastat 25 microgram/kg dose bolus regimen versus abciximab (including 2213 ACS patients, across the ACS spectrum, with both NSTEMI and STEMI patients) did not reveal any significant difference in the OR for death or MI at 30 days between the two agents (OR, 0.87 [0.56-1.35]; p=0.54). Similarly, there were no significant differences in 30-day mortality between Aggrastat and abciximab (OR, 0.73 [0.36-1.47]; p=0.38). Additionally, at the longest follow-up, death or MI was not significantly different between Aggrastat and abciximab (OR, 0.84 [0.59-1.21]; p=0.35).
TARGETstudy
In one study using a 10 microgram/kg bolus followed by a 0.15 microgram/kg/min infusion of Aggrastat, Aggrastat failed to demonstrate noninferiority to abcixi
