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 abciximab: the incidence of the composite primary endpoint (death, MI, or uTVR at 30 days) showed that abciximab was significantly more effective on clinically relevant endpoints, with 7.6% in the Aggrastat and 6.0% in the abciximab group (p=0.038), which was mainly due to a significant increase in the incidence of MI at 30 days (respectively 6.9% vs. 5.4%; p=0.04).
Distribution
Tirofiban is not strongly bound to plasma protein, and protein binding is concentration-independent in the range of 0.01–25 microgram/ml. The unbound fraction in human plasma is 35%.
The distribution volume of tirofiban in the steady state is about 30 litres.
Biotransformation
Experiments with 14C-labelled tirofiban showed the radioactivity in urine and faeces to be emitted chiefly by unchanged tirofiban. The radioactivity in circulating plasma originates mainly from unchanged tirofiban (up to 10 hours after administration). These data suggested limited metabolisation of t
