ASSENT 3 Plus

1
ASSENT-3 PLUS

• 1,639 patients with STEMI
• Chest pain lt 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
P0.080
P0.297
n821
n818
n821
n818
Enoxaparin TNK
UFH TNK
UFH TNK
Enoxaparin TNK
Wallentin et al, AHA 2002
3
ASSENT-3 PLUS Individual Endpoints
Recurrent MI
Death
ICH
Refractory Ischemia
P0.047
P0.028
P0.067
P0.234
Enoxaparin TNK
Enoxaparin TNK
UFH TNK
Enoxaparin TNK
UFH TNK
UFH TNK
Enoxaparin TNK
UFH TNK
Wallentin et al, AHA 2002
4
ASSENT-3 PLUS Bleeding Results
Stroke
Major Bleed
ICH
P0.026
P0.047
P0.168
Similar to prior studies
Enoxaparin TNK
Enoxaparin TNK
Enoxaparin TNK
UFH TNK
UFH 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 gt75 years old (6.71 vs. 0.76 p 0.04)
• females (5.15 vs. 1.09, p 0.02), and
• low body weight (lt60kg) 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
Age gt75
Age lt75
Death / MI / Refractory Ischemia
Death / MI / Refractory Ischemia
P0.694
P0.033
UFH TNK
Enoxaparin TNK
UFH TNK
Enoxaparin 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