Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction: the integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial.

OBJECTIVES

This study was designed to test the hypothesis that eptifibatide and reduced-dose tissue plasminogen activator (t-PA) will enhance infarct artery patency at 60 min in patients with acute myocardial infarction (AMI).

BACKGROUND

Combination fibrin and platelet lysis improves epicardial and myocardial reperfusion in AMI.

METHODS

Patients were enrolled in a dose finding (Phase A, n = 344) followed by a dose confirmation (Phase B, n = 305) protocol. All patients received aspirin and weight-adjusted heparin and underwent angiography at 60 and 90 min. In Phase A, eptifibatide in a single or double bolus (30 min apart) of 180, 180/90 or 180/180 microg/kg followed by an infusion of 1.33 or 2.0 microg/kg per min was sequentially added to 25 or 50 mg of t-PA. In Phase B, patients were randomized to: 1) double-bolus eptifibatide 180/90 (30 min apart) and 1.33 microg/kg per min infusion with 50 mg t-PA (Group I); 2) 180/90 (10 min apart) and 2.0 g/kg per min with 50 mg t-PA (Group II); or 3) full-dose, weight-adjusted t-PA (Group III).

RESULTS

In Phase A, the best rate of Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved using 180/90/1.33 microg/kg per min eptifibatide with 50 mg t-PA: 65% and 78% at 60 and 90 min, respectively. In Phase B, the incidence of TIMI flow grade 3 at 60 min was 42%, 56% and 40%, for Groups I through III, respectively (p = 0.04, Group II vs. Group III). The median corrected TIMI frame count was 38, 33 and 50, respectively (p = 0.02). TIMI major bleeding was reported in 8%, 11% and 6%, respectively; intracranial hemorrhage occurred in 1%, 3% and 2% of patients (p > 0.5 for both). The incidences of death (4%, 5% and 7%), reinfarction or revascularization at 30 days were similar among the three treatment groups.

CONCLUSIONS

In comparison with standard t-PA regimen, double-bolus eptifibatide (10 min apart) with a 48-h infusion and half-dose t-PA (Group II) is associated with improved quality and speed of reperfusion. The safety profile of this therapy is similar to that of other combination regimens.