1. INTRO AMI. INTEGRILIN AND. REDUCED DOSE. OF THROMBOLYTIC IN. ACUTE
INTRO AMI INTEGRILIN AND REDUCED DOSE OF THROMBOLYTIC IN ACUTE MYOCARDIAL INFARCTION

2. INTRO AMI Study Design Multi-national, multi-center enrollment
Open-label, dose finding phase
Sequential dose-escalation design
Confirmation phase (planned)

3. Purpose and Primary Endpoints
Integrilin INTRO AMI
Purpose and Primary Endpoints
To evaluate the incidence of TIMI 3 flow at 60 minutes
To evaluate the incidence of TIMI bleeding during acute hospitalization

4. Integrilin INTRO AMI Other Endpoints: ST segment resolution at 3 hours
TIMI frame count in IRA
TIMI flow at 90 minutes, if available

5. Integrilin INTRO AMI Clinical Endpoints
Death - cardiovascular or other
Reinfarction
Stroke (CT or MRI documentation)
Hemorrhagic
non-hemorrhagic
Urgent target vessel revascularization
CABG or PTCA, including initial PTCA for TIMI 0-2 flow

6. INTRO AMI Study Design Acute MI <6 hours duration
60 minute angiography
PTCA if clinically indicated
90 minute angiography
Rescue PTCA for TIMI 1-2 flow
Study drug infusion for 72 hours

7. INTRO AMI Study Design Heparin 4000 IU IV bolus ASA 325 mg / day
800 IU/hr IV infusion
aPTT seconds
ASA 325 mg / day
PCI at discretion of investigator

8. Integrilin Intro AMI Study Protocol

9. Integrilin Intro AMI Patient Enrollment
Total Enrolled: 190
Level A (180/1.33) = 35
Level B ( /1.33) = 37
Level E (180/ /35) = 33
Level F ( / /35) = 53
Level G (180/2.0 Initial + 15/35) = 32

10. TIMI Grade 3 Flow at 60 Minutes33 30 31 30 48
Integrilin bolus / /90
Integrilin infusion
tPA bolus
tPA infusion

11. TIMI Grade 3 Flow at 90 Minutes33 30 31 30 48
Integrilin bolus / /90
Integrilin infusion
tPA bolus
tPA infusion

12. Bleeding events Site adjudication
Level A (N=35)
Moderate - 2 pts.
Severe - 3 pts.
Level E (N = 33)
Moderate - 5
Severe - 2
Level G (N = 32)
Moderate - 1 pts.
Severe - 0 pts
Level B (N=35)
Moderate - 6 pts.
Severe - 2 pts.
Level F (N = 53)
Moderate - 5
Severe - 0

13. Preliminary Results - OVERALL TIMI Major Bleeding Events
Single bolus Integrilin
Level A = 3/35
CABG related = 1
Level E = 3/33
Level G = 6/32
CABG related = 2
12/100
4 CABG related
Double bolus Integrilin
Level B = 6/35
CABG related = 3
Level F = 7/53
CABG related = 4
13/88
7 CABG related

14. Integrilin INTRO AMI Summary and Conclusions
Efficacy
The combination of Integrilin and reduced dose rt-PA achieves enhanced TIMI 3 flow at 60 and 90 minutes.
Greatest increase in TIMI 3 flow results from a double bolus of Integrilin and with half-dose rt-PA (15/35mg).
Safety
There appears to be a clinically acceptable increase in bleeding related primarily to femoral access site.

15. Integrilin INTRO AMI Conclusions
The use of Integrilin in combination with low dose fibrinolytics is a promising therapeutic strategy in acute myocardial infarction.
Large scale clinical-outcome studies will be required to further assess the benefits of this strategy.