In the PRISM trial [1], treatment with the GP IIb/IIIa receptor antagonist tirofiban was associated with a reduction of 32% in the primary endpoint of death/MI or recurrent ischemia at 48 hours (p = 0.007), compared to aspirin and heparin monotherapy.

In the PRISM-PLUS trial [2], which involved 1905 patients with unstable angina and non-ST-elevation MI, tirofiban plus heparin lead to a 32% risk reduction of death/MI or refractory ischemia at 7 days compared to placebo, i.e., heparin plus aspirin (12.9% vs 17.9%, respectively, p=0.004). The benefit was sustained at 30 days (death or MI at 30 days: 11.9% vs 8.9%, p=0.03), and 6 months. The risk reduction was observed among all subgroups and irrespective of treatment strategy (death or MI reduction: 25% reduction in medically treated patients, 35% reduction in patients undergoing PCI, and 30% reduction in patients undergoing CABG).

In the PURSUIT trial [3], treatment with the synthetic GP IIb/IIIa inhibitor eptifibatide was associated with a 10% reduction in the primary endpoint of death or MI at 30 days (14.2% for eptifibatide group vs. 15.7% for placebo group, p=0.042). Although benefit was seen in patients undergoing early PCI (31% reduction in death or MI at 30 days, p=0.01), no significant benefit was seen in those treated medically, with late PCI, or CABG.

In both PRISM-PLUS and PURSUIT, patients who did not receive heparin had a higher rate of death or MI. In patients not receiving heparin in the PURSUIT study, eptifibatide was associated with a trend towards an increased 30-day death and MI compared to placebo (13.0% vs 9.2%, p=0.078) [3]. Thus, concomitant heparin therapy needs to be administered along with intravenous synthetic GP IIb/IIIa receptor blocker therapy.

1. The PRISM-PLUS Investigators. N Engl. J Med 1998; 338 1488-1497.

2. The PURSUIT Trial Investigators. N Engl J Med 1998; 339 436-443.

3. Peterson JG, Lauer MA, Sapp SK, et al. Heparin use is required for clinical benefit of GP IIb/IIIa Inhibitor Eptifibatide in Acute Coronary Syndromes: Insights from the PURSUIT trial. Circulation 1998; 98 (Suppl 1): 360.


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