1. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : Background
Advantages of Antithrombotic Agents in AMI:
May promote speed and efficacy of thrombolysis May suppress the rate of rethrombosis The safety and efficacy of low molecular weight heparins have not been compared to unfractionated heparin when used in combination with thrombolytic agents in ST segment elevation MI
A Ross, Late Breaking Clinical Trial Results, ACC 2000

2. HART-II Protocol Design N = 400
ST  MI < 12H
Age > 18 years
N = 400
ASA and tPA, 100 mg
Front Loaded 90 min regimen
Enoxaparin
30 mg IV bolus
1 mg/kg SC at 15” Q12 hrs for 72 hrs
Unfractionated Heparin
5,000 u bolus (4,000 < 67kg)
15 unit/kg IV infusion for 77 hrs
Endpoints:
Blinded Core Lab Analysis of IRA patency at 90 min and 5-7 days
Safety
A Ross, Late Breaking Clinical Trial Results, ACC 2000

3. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : Clinical Sites
Steering Committee Members
Merril Knudtson, MD - Canada
Conor Lundergan, MD - USA
Peter Molhoek, MD - The Netherlands
Allan M. Ross, MD, Chaiman - USA * * *
DSMB Members
Pierre Théroux, MD, Chairman - Canada
Marcel van de Brand, MD - The Netherlands
Werner Hacke, MD - Germany
David Sheps, MD - USA
Freek Verheurgt, MD - The Netherlands
Janet Wittes, PhD - USA
Principal Sponsor
Aventis (RPR)
Operations
Bert de Jong, MD - USA
Yasmine Draoui, MS - USA
Lorna Regalado - USA
Whitney Schwartz - USA
A Ross, Late Breaking Clinical Trial Results, ACC 2000

4. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : Baseline Variables
Unfractionated Enoxaparin
Heparin
Mean Age (yrs)
Male Gender (%)
Mean Weight (kg)
Time, Pain to Rx (hrs)
Current Smoker (%)
Prior MI (%)
LAD Infarct (%)
A Ross, Late Breaking Clinical Trial Results, ACC 2000

5. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : IRA Patency at 90 Minutes
81.1
75.1
p =NS
47.6
52.9
A Ross, Late Breaking Clinical Trial Results, ACC 2000

6. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : Equivalence Analysis
IRA Patency at 90 min
85.9
80.1
74.4
Enox
81.3
69.0
UFH 90 85 80
75.1 70 65 60
Patency, %
A Ross, Late Breaking Clinical Trial Results, ACC 2000

7. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : Equivalence Analysis
Hypothesis : Enoxaparin is not inferior to unfractionated heparin, with a minimum acceptable difference of 10% (Delta) in patency (TIMI 2+3 flow)
Conclusion of Equivalence
Difference in patency rate [ ]
-10%
-2% % (observed delta)
12%
Conclusion: The lower bound of the 90% CI of the difference in patency between Enox and UFH is -2%, far from the -10% equivalence limit, and close to the superiority limit (0) : equivalence hypothesis is confirmed
A Ross, Late Breaking Clinical Trial Results, ACC 2000

8. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : Reocclusion within one Week
TIMI 2, 3  0, 1
TIMI 3  0, 1 %
UFU
Enox
UFU
Enox
A Ross, Late Breaking Clinical Trial Results, ACC 2000

9. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART-II : Clinical Events
Bleeding
Intracranial Hemorrhage 2 (1.0%) 2 (1.0%)
Major Hemorrhage (TIMI) 3.0% 3.6%
Transfusion  2U pRBC 7.1% 5.6%
Hgb decline  3gm/dl 10.7% 12.8%
Fatalities
In Hospital 4.5% 4.0%
30 day 5.0% 5.0%
UFH
Enox
A Ross, Late Breaking Clinical Trial Results, ACC 2000

10. A Ross, Late Breaking Clinical Trial Results, ACC 2000
HART- II: Conclusions
Trend toward higher 90 minute patency with enoxaparin vs. unfractionated heparin
Trend toward less frequent reocclusion of IRA with enoxaparin
Similar rates of major bleeding with enoxaparin and UFH
A Ross, Late Breaking Clinical Trial Results, ACC 2000