1. OASIS-2 OASIS-2 OVERVIEW 10,141 patients evaluating Hirudin vs. Heparin and 3712 patients evaluating Warfarin vs. Standard Therapy International (16 Countries) at 360 Centres Recruitment: August 1996 - April 1, 1998 Follow Up Completed: September, 1998 Coordinated by CCC, GISSI and National Coordinating Centres As at January 28, 1999

2. OASIS-2 OASIS-2 DESIGN Main Study: I.V. Hirudin vs. I.V. Heparin -72 hours infusion, randomized double blind -Hirudin: 0.4 mg/kg Bolus + 0.15 mg/kg/hr Infusion -Heparin: 5,000 units Bolus + 15 units/kg/hr Infusion Substudy: Long term Warfarin vs. Standard Therapy -Long term prophylaxis, open comparison -Randomization made 12-30 hrs after initial. Rand. As at January 28, 1999

3. OASIS-2 Baseline Characteristics 1 As at January 28, 1999

4. OASIS-2 Direction of Infusion Adjustments As at January 28, 1999

5. OASIS-2 Hospital Non-study Medications 1 As at January 28, 1999

6. OASIS-2 Hospital Non-study Medications 2 As at January 28, 1999

7. OASIS-2 Hospital Non-study Medications 3 As at January 28, 1999

8. OASIS-2 Mean aPTTs Average of Mean aPTT per Patient with STD bars (sec) As at January 28, 1999

9. OASIS-2 PRIMARY AND SECONDARY OUTCOMES AT 7 DAYS As at January 28, 1999

10. OASIS-2 RADIOLOGICAL EVIDENCE OF HEART FAILURE As at January 28, 1999

11. Summary of Effects of Hirudin Compared to Heparin on Death/MI In Acute Ischemic Syndromes Without Thrombolytics With Thrombolytics Overall RR p 0.72 0.0002 0.83 0.004 0.90 0.057 0.89 0.34 0.88 0.19 0.88 0.13 0.78 0.0004 0.84 0.002 0.90 0.016 315 233 504 426 810 751 155 140 249 223 358 323 470 373 753 649 1168 1074 © OASIS-2 As at January 28, 1999

12. CV Death/MI Days 1 to 7 Days of Follow-up Cumulative Hazard Rates CV Death/MI/Refractory Angina Days 1 to 7 © OASIS-2 As at January 28, 1999

13. CV Death/MI Days 1 to 35 Days of Follow-up Cumulative Hazard Rates CV Death/MI/Refractory Angina Days 1 to 35 © OASIS-2 As at January 28, 1999

14. PRIMARY AND SECONDARY OUTCOMES CVD/MI CVD/MI/RFA RR=0.76 p=0.039 RR=0.84 p=0.077 RR=0.78 p=0.019 RR=0.82 p=0.0125 % © OASIS-2 As at January 28, 1999

15. OASIS-2 STROKES AT DAY 7 As at January 28, 1999

16. OASIS-2 MAJOR BLEEDS UP TO DAY 7 As at January 28, 1999

17. OASIS-2 CARDIAC INTERVENTIONS UP TO DAY 7 As at January 28, 1999

18. Refractory Angina up to Day 7 © OASIS-2 As at January 28, 1999

19. OASIS-2 Combined results of the OASIS-1 and OASIS-2 Studies with r-hirudin As at January 28, 1999

20. OASIS 1 and 2: Conclusions 1. Hirudin is more effective than heparin in preventing ischemic events in UA by about 25% during treatment 2. No evidence of rebound 3. At 7 days -Primary endpoint (CV Death/MI) 19% (95% CI 2% to 33%) -Secondary endpoint (CV Death/MI/RFA) 20% (95% CI: 6% to 32%) -Need for Intervention 17% (95% CI: 5% to 28%) -Heart Failure 30% (95% CI: 10% to 46%) Early differences persist up to 35 days © OASIS-2 As at January 28, 1999