tially randomized to AGGRASTAT alone (no heparin). This arm was stopped when the group was found, at an interim look, to have greater mortality than the other two groups.
The primary endpoint of the study was a composite of refractory ischemia, new MI and death within 7 days. There was a 32% risk reduction in the overall composite primary endpoint. The components of the composite were examined separately and the results are shown in Table 5. Note that the sum of the individual components may be greater than the composite (if a patient experiences multiple component events only one event counts towards the composite).
Table 5 Primary outcomes at 7 days in PRISM-PLUS
Endpoint
AGGRASTAT+
Heparin
(n=773)
Heparin
(n=797)
Risk Reduction
p-value
Death, new MI, and refractory ischemia at 7 days
12.9%
17.9%
32%
0.004
Death
1.9%
1.9%
---
---
MI
3.9%
7.0%
47%
0.006
Refractory Ischemia
9.3%
12.7%
30%
0.023
The benefit seen at 7 days was maintained over time. The risk reduction in the composite endpoint at 30 days and 6 months is shown in the Kaplan-Meier curve below.
figure1
Figure 1. Time to first event of death, new MI, or refractory ischemia in PRISM-PLUS
An analysis of the results by sex suggests that women who are medically managed or who undergo subsequent PTCA/atherectomy may receive less benefit from AGGRASTAT (95% confidence limits for relative risk of 0.61-1.74) than do men (0.43-0.89) (p=0.11). This difference may be a true treatment difference, the effect of other differences in these subgroups, or a chance occurrence.
Approximately 90% of patients in the PRISM-PLUS study underwent coronary angiography and 30% underwent angioplasty/atherectomy during the first 30 days of the study. The majority of these patients continued on study drug throughout these procedures. AGGRASTAT was continued for 12-24 hours (average 15 hours) after angioplasty/atherectomy. The effects of AGGRASTAT at Day 30 did not appear to differ among sub-populations that did or did not receive PTCA or CABG, both prior to and after the procedure.
PRISM (Platelet Receptor Inhibition for Ischemic Syndrome Management)
In the PRISM study, a randomized, parallel, double-blind study, 3232 patients with NSTE-ACS intended to be managed without coronary intervention were randomized to AGGRASTAT (initial dose of 0.6 mcg/kg/min for 30 minutes followed by 0.15 mcg/kg/min for 47.5 hours) or heparin (5000-unit intravenous bolus followed by an infusion of 1000 U/h for 48 hours). The mean age of the population was 62 years; 32% of the population was female and 25% had non-ST elevation MI on presentation. Thirty percent had no ECG evidence of cardiac ischemia. Exclusion criteria were similar to PRISM-PLUS. The primary endpoint was the composite endpoint of refractory ischemia, MI or death at the end of the 48-hour drug infusion. The results are shown in Table 6.
Table 6 Primary outcomes in PRISM – Cardiac Ischemia Events
Composite Endpoint (death, MI, or refractory ischemia)
AGGRASTAT
(n=1616)
Heparin
(n=1616)
Risk Reduction
p-value
2 Days (end of drug infusion)
3.8%
5.6%
33%
0.015
7 Days
10.3%
11.3%
10%
0.33
In the PRISM study, no adverse effect of AGGRASTAT on mortality at either 7 or 30 days was detected.
