The reduction of MI in patients receiving Aggrastat appeared early during treatment (within the first 48 hours) and was maintained through 6 months. In the 30% of patients who underwent angioplasty/atherectomy during initial hospitalisation, there was a 46% RR (8.8% vs. 15.2%) for the primary composite endpoint at 30 days as well as a 43% RR (5.9% vs. 10.2%) for death or MI.

Based on a safety study, the concomitant administration of Aggrastat (30 minute loading dose of [0.4 microgram/kg/min] followed by a maintenance infusion of 0.1 microgram/kg/min for up to 108 hours) with enoxaparin (n=315) was compared to the concomitant administration of Aggrastat with unfractionated heparin (n=210) in patients presenting with UA and NQWMI. Patients in the enoxaparin group received a 1.0 milligram/kg subcutaneous injection every 12 hours for a period of at least 24 hours and a maximum duration of 96 hours. Patients randomised to unfractionated heparin received a 5000-unit intravenous bolus followed by a maintenance infusion of 1000 units per hour for at least 24 hours and a maximum duration of 108 hours. The total TIMI bleed rate was 3.5% for the Aggrastat/enoxaparin group and 4.8% for the Aggrastat/unfractionated heparin group. Although there was a significant difference in the rates of cutaneous bleeds between the two groups (29.2% in the enoxaparin converted to unfractionated heparin group and 15.2% in the unfractionated heparin group), there were no TIMI major bleeds (see section 4.4) in either group. The efficacy of Aggrastat in combination with enoxaparin has not been established.

PRISM PLUS trial was conducted at a time when the standard of care of managing acute coronary syndromes was different from that of present times in terms of oral platelet ADP receptor (P2Y12) antagonists use and the routine use of intracoronary stents.

ADVANCE study

The ADVANCE study determined the safety and efficacy of the Aggrastat 25 microgram/kg dose bolus regimen as compared with placebo in patients undergoing elective or urgent PCI who exhibit high-risk characteristics including the presence of at least one coronary narrowing ≥70% and diabetes, need for multi-vessel intervention, or NSTE-ACS. All patients received unfractionated heparin, acetylsalicylic acid (ASA) and a thienopyridine loading dose followed by maintenance therapy. A total of 202 patients were randomised to either Aggrastat (25 microgram/kg bolus IV over 3 minutes followed by a continuous IV infusion of 0.15 microgram/kg/minute for 24-48 hours) or Placebo given immediately before PCI.

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 rando