nts received ASA unless contraindicated. Study drug was initiated within 12 hours after the last anginal episode. Patients were treated for 48 hours, after which they underwent angiography and possibly angioplasty/atherectomy, if indicated, while Aggrastat was continued. Aggrastat was infused for a mean period of 71.3 hours.
The combined primary study end-point was the occurrence of refractory ischaemia, myocardial infarction or death at seven days after the start of Aggrastat.
At 7 days, the primary end-point, there was a 32% risk reduction (RR) (12.9% vs. 17.9%) in the Aggrastat group for the combined end-point (p=0.004): this represents approximately 50 events avoided for 1,000 patients treated. After 30 days the RR for the composite end-point of death, MI, refractory ischaemic conditions, or readmissions for UA was 22% (18.5% vs. 22.3%; p=0.029). After six months the relative risk of composite of death, MI, refractory ischaemic conditions, or readmissions for UA was reduced by 19% (27.7% vs. 32.1% ; p=0.024).
Regarding the,composite of death or MI, at seven days for the Aggrastat group there was a 43% RR (4.9% vs. 8.3%; p=0.006); at 30 days the RR was 30% (8.7% vs. 11.9%; p=0.027) and at 6 months the RR was 23% (12.3% vs. 15.3%; p=0.063).
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 unfractionate
