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CLINICAL STUDY: MYOCARDIAL INFARCTION

Eptifibatide and low-dose tissue plasminogen activator in acute myocardial infarction

The integrilin and low-dose thrombolysis in acute myocardial infarction (INTRO AMI) trial

Sorin J. Brener, MD, FACC^*,*, Uwe Zeymer, MD, FACC, A. A. Jennifer Adgey, MD, FACC, Thomas R. Vrobel, MD, FACC, Stephen G. Ellis, MD, FACC^*, Karl-Ludwig Neuhaus, MD, FACC¹, Nadine Juran, RN^*, Thomas B. Ivanc, MS^*, E. Magnus Ohman, MD, FACC^||, John Strony, MD, FACC^¶, Michael Kitt, MD, FACC^#, Eric J. Topol, MD, FACC^* for the INTRO AMI Investigators

^* Cleveland Clinic Foundation, Cleveland, Ohio, USA
Staedtische Kliniken, Kassel, Germany
Royal Victoria Hospital, Belfast, Ireland
MetroHealth Medical Center, Cleveland, Ohio, USA
^|| Duke Medical Center, Durham, North Carolina, USA
^¶ Schering-Plough Research Institute, Kenilworth, New Jersey, USA
^# COR Therapeutics, South San Francisco, California, USA

Manuscript received August 2, 2001; revised manuscript received October 26, 2001, accepted November 7, 2001.

^* Reprint requests and correspondence: Dr. Sorin J. Brener, 9500 Euclid Ave., Desk F-25, Cleveland, Ohio 44195, USA
breners{at}ccf.org

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 µg/kg followed by an infusion of 1.33 or 2.0 µg/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 µg/kg per min infusion with 50 mg t-PA (Group I); 2) 180/90 (10 min apart) and 2.0 µg/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 µg/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.

Abbreviations and Acronyms   GUSTO   AMI   acute myocardial infarction   aPTT   activated prothrombin time   cTFC   corrected TIMI frame count   CK-MB   creatine kinase-MB   ECG   electrocardiogram   GP   glycoprotein   GUSTO   Global Utilization To Open occluded coronary arteries   ICH   intracranial hemorrhage   LAD   left anterior descending artery   TIMI   Thrombolysis In Myocardial Infarction   t-PA   tissue plasminogen activator

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