1. ASSENT-3 PLUS 1,639 patients with STEMI Treatment Group A
Chest pain < 6 hrs
Pt evaluated at home or in ambulance by emergency medical team
12-lead ECG transmitted to ED from the ambulance
Pt randomized and treatment started during transport
Treatment Group A
Enoxaparin + TNK
(n = 818)
Treatment Group B
UFH + TNK
(n = 821)
Endpoints:
Primary Efficacy– 30 day Death or In-hospital MI or Refractory Ischemia
Primary Efficacy plus Safety - 30 day Death or In-hospital MI, Refractory Ischemia, ICH or Major Bleed
Wallentin et al, AHA 2002

2. ASSENT-3 PLUS: Primary Endpoints
Death / MI / Refractory Ischemia/ ICH / Major Bleed
Death / MI / Refractory Ischemia
P=0.080
P=0.297
n=818
n=821
n=818
n=821
Enoxaparin
+ TNK
UFH
+ TNK
Enoxaparin
+ TNK
UFH
+ TNK
Wallentin et al, AHA 2002

3. ASSENT-3 PLUS: Individual Endpoints
Death
Recurrent MI
Refractory Ischemia
ICH
P=0.028
P=0.067
P=0.047
P=0.234
Enoxaparin
+ TNK
UFH
+ TNK
Enoxaparin
+ TNK
UFH
+ TNK
Enoxaparin
+ TNK
Enoxaparin
+ TNK
UFH
+ TNK
UFH
+ TNK
Wallentin et al, AHA 2002

4. ASSENT-3 PLUS: Bleeding Results
Stroke
ICH
Major Bleed
P=0.026
P=0.047
P=0.168
Similar to prior studies
Enoxaparin
+ TNK
UFH
+ TNK
Enoxaparin
+ TNK
UFH
+ TNK
Enoxaparin
+ TNK
UFH
+ TNK
Wallentin et al, AHA 2002

5. ASSENT 3 ICH Subgroups
In subgroup analysis, ICH bleeding was greater in the enoxaparin group in
patients >75 years old (6.71 vs. 0.76% p = 0.04)
females (5.15% vs. 1.09%, p = 0.02), and
low body weight (<60kg) patients (5.17% vs. 0%, p = 0.08)
There was a non-statistically significant trend toward increased major bleeding in the enoxaparin group (4.04% vs. 2.80%, p = 0.168).
Twenty-five percent of the patients in each arm continued on to PCI. None of those patients experienced ICH bleeding, suggesting full-dose TNKase is safe in the cath lab.

6. Why Was There More Bleeding in the Enoxaparin Group?
Administration of additional enoxaparin was frequent
The heparin bag is “visible”, the bolus of enoxaparin is “invisible” to people caring for the patient subsequently
Occurred more in Europe
This was a higher risk population

7. ASSENT-3 PLUS: Primary Endpoint by Age Group
Death / MI / Refractory Ischemia
Death / MI / Refractory Ischemia
P=0.033
P=0.694
Enoxaparin
+ TNK
UFH
+ TNK
Enoxaparin
+ TNK
UFH
+ TNK
Wallentin et al, AHA 2002

8. ASSENT 3 Plus Supports the Concept that Time is Muscle
Symptom onset to treatment times were reduced by 45 minutes.
Fifty percent of patients were treated within 2 hours which represents a significant improvement over ASSENT-3 in which only 29% of the more than 4,000 patients receiving the same regimens in the hospital setting were treated within the same time period.
Earlier treatment was associated with improved outcomes: 30 day mortality 4.4% (0-2hr), 6.2% (2-4hr), 10.4% (4-6hr).
This data, combined with a meta-analysis of all pre-hospital thrombolysis studies showing a 16% improvement in mortality (Morrison et.al, JAMA May 2000), further supports the concept of “time is muscle” and early treatment.
CM Gibson 2002

9. ASSENT-3 PLUS: Summary
In the pre-hospital setting, treatment with enoxaparin plus TNK did not provide significant additional benefit over treatment with UFH plus TNK for STEMI.
Pre-hospital TNK plus heparin does, however, appear to be safe and lower treatment times
Reduced or weight-adjusted dosing of enoxaparin may be warranted in elderly and low weight patients
Use of reduced dose enoxaparin in addition to TNK will be further investigated in the upcoming EXTRACT-TIMI trial
CM Gibson 2002