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Design
- Multicenter, parallel, double-blind study involving 1915 patients with acute coronary syndromes (ACS) and unstable angina or non–Q-wave/non–ST-elevation (NSTE) myocardial infarction (MI) in the previous 12 hours
- Patients randomized to AGGRASTAT (0.6 µg/kg/min for 30 minutes and 0.15 µg/kg/min infusion; n=345), AGGRASTAT (0.4 µg/kg/min for 30 minutes and 0.1 µg/kg/min infusion) plus heparin (n=773), or heparin alone (n=797) for 48 hours
- All patients received acetylsalicylic acid (ASA) at randomization and daily thereafter unless contraindicated. Invasive assessment was deferred for the first 48 hours. Patients undergoing early percutaneous coronary intervention continued the study drug for 12 to 24 hours afterward.
- The primary endpoint was a composite of death, MI, or refractory ischemia within seven days after randomization. Rehospitalization for unstable angina was also counted in the composite primary endpoint when assessed at seven days, 30 days, and six months.
Results
- The nonheparin arm was discontinued early, and its data were not included in this analysis.
- Incidence of the primary endpoint was 12.9% with AGGRASTAT plus heparin and 17.9% with heparin alone (32% risk reduction, p=0.004).
- The risk of death or MI was reduced by 43% (p=0.006) at day 7 and by 30% (p=0.03) at day 30 with AGGRASTAT plus heparin versus heparin alone.
- Frequency of major bleeding did not differ between the groups. Thrombocytopenia (platelet count ≤90,000/mm3) occurred more frequently with AGGRASTAT plus heparin versus heparin alone (1.9% vs. 0.8%, p=0.07), but the difference was not statistically significant. Platelet counts returned to normal after cessation of the study-drug infusions, without any other clinical sequelae.
Conclusion
- AGGRASTAT plus heparin and ASA was associated with a lower incidence of ischemic events (death, MI, refractory ischemia, or rehospitalization for unstable angina) in patients with ACS than in patients who received only heparin and ASA.
In the PRISM-PLUS study, patients with ACS and unstable angina or non–Q-wave/NSTE MI who received AGGRASTAT and ASA showed a significantly lower risk of death, MI, refractory ischemia, and rehospitalization for unstable angina at days 2 (p=0.08), 7 (p=0.004), 30 (p=0.03), and six months (p=0.02) than those who received heparin and ASA.
*or rehospitalization for unstable angina
Adapted from PRISM-PLUS Study Investigators.2
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