Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction

Abstract

Background: Antithrombotic therapy improves the prognosis of patients with acute coronary syndromes, yet the syndromes remain a therapeutic challenge. We evaluated tirofiban, a specific inhibitor of the platelet glycoprotein IIb/IIIa receptor, in the treatment of unstable angina and non-Q-wave myocardial infarction.

Methods: A total of 1915 patients were randomly assigned in a double-blind manner to receive tirofiban, heparin, or tirofiban plus heparin. Patients received aspirin if its use was not contraindicated. The study drugs were infused for a mean (+/-SD) of 71.3+/-20 hours, during which time coronary angiography and angioplasty were performed when indicated after 48 hours. The composite primary end point consisted of death, myocardial infarction, or refractory ischemia within seven days after randomization.

Results: The study was stopped prematurely for the group receiving tirofiban alone because of excess mortality at seven days (4.6 percent, as compared with 1.1 percent for the patients treated with heparin alone. The frequency of the composite primary end point at seven days was lower among the patients who received tirofiban plus heparin than among those who received heparin alone (12.9 percent vs. 17.9 percent; risk ratio, 0.68; 95 percent confidence interval, 0.53 to 0.88; P=0.004). The rates of the composite end point in the tirofiban-plus-heparin group were also lower than those in the heparin-only group at 30 days (18.5 percent vs. 22.3 percent, P=0.03) and at 6 months (27.7 percent vs. 32.1 percent, P=0.02). At seven days, the frequency of death or myocardial infarction was 4.9 percent in the tirofiban-plus-heparin group, as compared with 8.3 percent in the heparin-only group (P=0.006). The comparable figures at 30 days were 8.7 percent and 11.9 percent (P=0.03), respectively, and those at 6 months were 12.3 percent and 15.3 percent (P=0.06). The benefit was consistent in the various subgroups of patients and in those treated medically as well as those treated with angioplasty. Major bleeding occurred in 3.0 percent of the patients receiving heparin alone and 4.0 percent of the patients receiving combination therapy (P=0.34).

Conclusions: When administered with heparin and aspirin, the platelet glycoprotein IIb/IIIa receptor inhibitor tirofiban was associated with a lower incidence of ischemic events in patients with acute coronary syndromes than in patients who received only heparin and aspirin.