1. ADMIRALADMIRAL Abciximab before Direct Angioplasty and Stenting in Myocardial Infarction Regarding Acute and Long term follow-up ADMIRAL Study ADMIRAL

2. ADMIRAL 1999, Oral Presentation Aim of the Study To demonstrate the superiority of abciximab over placebo in primary PTCA with stenting in acute myocardial infarction ESC

3. ADMIRAL 1999, Oral Presentation Design-Inclusion Criteria Multicenter Randomized Double-Blind Placebo Controlled 2 x 150 patients included-July 1997-Dec.1998 –> 18 years old –Clinical Diagnosis of AMI ( ischemic pain > 30 min. ) –Onset of symptoms < 12 hours –ST elevation > 1 mm in at least 2 contiguous leads –Referred for Urgent Primary PTCA –Written informed consent before randomization ESC

4. ADMIRAL 1999, Oral Presentation Design-Exclusion Criteria Major Exclusion Criteria –Hemorrhagic risk factors –Current episode previously treated by thrombolytics –Cardiogenic shock –Life expectancy < 1 year Contraindications to PTCA –Stenosis < 50% and TIMI 3 Flow in the IRA –Occluded vessel of minor angiographic importance –Culprit lesion not visualized ESC

5. ADMIRAL 1999, Oral Presentation Criteria for Stent Implantation Coronary artery diameter > 2.5 mm Accessible by a stent No massive calcification ESC

6. ADMIRAL 1999, Oral Presentation Study Drugs Abciximab or Placebo 0.25 mg/kg bolus plus 0.125  g/kg/min 12-hour infusion, as soon as AMI is diagnosed and before any sheath insertion, administered either in –the ambulance (MICU) –the emergency room –the catherization laboratory Unfractionated heparin –Prior to intervention : 70 U/kg as a bolus (<7000 U) –Maintain ACT > 200 seconds pre and post PTCA until the second angiogram –Infusion rate of 7 U/kg/hour Aspirin : 100-325 mg once daily during 6 months Ticlopidine : 250 mg twice daily during 30 days if stent is used ESC

7. ADMIRAL 1999, Oral Presentation Design AMI < 12 hours randomization Abciximab + Heparin, ASA, Ticlopidine Placebo + Heparin, ASA, Ticlopidine First Coronary Angiography PTCA + Stent First Coronary Angiography PTCA + Stent Coronary Angiography at 24 h and 6 Months Coronary Angiography at 24 h and 6 Months Clinical evaluation (24 h, 30 Days and 6 Months ESC

8. ADMIRAL 1999, Oral Presentation Male (%)85.278.7 Age (years)59.6 + 13.062.1 + 12.8 Weight (kg)75.9 + 12.576.5 + 15.1 Prior MI (%)14.1 7.3* Prior UA (%)8.77.3 Prior Stable Angina (%)4.74.7 Prior PTCA (%)6.7 2.7* Prior Stent (%)0.10.1 Prior CABG (%)2.02.7 CAD Family History (%)28.928.7 Abciximab n = 150 Demographics Placebo n = 150 * p < 0.05 ESC

9. ADMIRAL 1999, Oral Presentation Demographics Smoker (%)45.039.3 Hypertension (%)39.341.3 Diabetes (%)15.420.0 Hyperlipidemia (%)39.637.3 Killip I (%)89.989.3 Abciximab n = 150 Placebo n = 150 ESC

10. ADMIRAL 1999, Oral Presentation Procedures Initial coronary angiogram (%) 98.799.3 Balloon angioplasty (%)90.694.0 Stent placed (%)83.986.0 24-hour Coronary Angiogram (%) 84.687.3 Abciximab n = 150 Placebo n = 150 ESC

11. ADMIRAL 1999, Oral Presentation Procedures Stent placed (%) 83.986.0 Saint-Come stent placed (%)65.164.6 Number of stent(s) / patient (%) 1 70.465.9 221.624.8 3 or more8.09.3 Primary Success Rate (%)94.494.6 Abciximab n = 150 Placebo n = 150 ˆ ESC

12. ADMIRAL 1999, Oral Presentation Medications Aspirin (%) 96.696.0 Ticlopidine (%)83.284.7 Received Study Drug Agent (%) –Bolus 100.099.3 –Bolus + Infusion99.096.7 Prehospital administration (MICU)10.711.3 Emergency Room administration14.115.3 CCU or Cath Lab administration75.273.4 Abciximab n = 150 Placebo n = 150 ESC

13. ADMIRAL 1999, Oral Presentation Time to Treatments Time from onset of chest pain: –to treatment (hrs)3.2 + 2.53.5 + 2.4 –to bolus (hrs)3.7 + 2.14.1 + 2.5 –to coronary angiogram (hrs)3.9 + 2.14.4 + 2.6 –to PTCA (hrs)4.1 + 2.14.6 + 2.6 Abciximab n = 150 Placebo n = 150 ESC

14. ADMIRAL 1999, Oral Presentation AMI Characteristics Anterior AMI (%)35.840.7 Inferior AMI (%)50.746.7 Other AMI (%)14.512.6 Right Coronary Artery (%)38.035.3 Left Anterior Desc. Artery (%)33.334.0 Circumflex Coronary Artery (%)9.310.0 Other Coronary Arteries (%)18.719.4 Vein Graft (%)0.71.3 Abciximab n = 150 Placebo n = 150 ESC

15. ADMIRAL 1999, Oral Presentation Primary Endpoint Percentage of ischemic events within the first 30 days: –Death –Recurrent MI –Urgent target vessel revascularization (PTCA or CABG) Urgent TVR: performed within 24 hours from the onset of a new acute ischemic episode Recurrent MI –within 24 hours of study entry: CK or CK-MB definitions –between 24 h and 7 days: ECG or CK-MB definitions –> 7 days: ECG or CK-MB definitions ESC

16. ADMIRAL 1999, Oral Presentation Angiographic Results: TIMI 3 flow rates 10.3 83.7 84.4 89.9 82.5 21.0 90.4 92.0 0 20 40 60 80 100 InitialAfter BalloonAfter stent24-hours % of Patients PlaceboAbciximab p < 0.02 p < 0.01 ESC

17. ADMIRAL 1999, Oral Presentation Left Ventricular Function Abciximab n = 150 Placebo n = 150 p < 0.05 51.4 54.6 0 25 50 75 24-hour LVEF (%) ESC p < 0.05

18. ADMIRAL 1999, Oral Presentation Primary Endpoint (30 days) 7.3 15.3 0 5 10 15 20 % of Patients p = 0.02 - 52.3 % Death, Recurrent MI, Urgent TVR Placebo n = 150 Abciximab n = 150 ESC

19. ADMIRAL 1999, Oral Presentation Primary Endpoint Components (30 days) 7.3 3.3 2.0 6.7 1.3 0 5 10 DeathRecurrent MIUrgent TVR % of Patients PlaceboAbciximab p = 0.33 - 54.8% p = 0.65 - 35.0% p = 0.02 - 80.0% ESC

20. ADMIRAL 1999, Oral Presentation Secondary Endpoint (30 days) Death, Recurrent MI, Any Revascularization 13.3 22.0 0 10 20 30 % of Patients p = 0.03 - 39.5 % Placebo n = 150 Abciximab n = 150 ESC

21. ADMIRAL 1999, Oral Presentation Bleeding Events 1.3 6.7 2.6 4.0 0 2 4 6 8 10 MajorMinor % of Patients PlaceboAbciximab p = 0.50 p = 0.02 ESC

22. ADMIRAL 1999, Oral Presentation Major Bleeding Events 2.6 0.9 1.7 2.0 4.0 0 2 4 6 8 10 TotalCABG relatedNon-CABG related % of Patients PlaceboAbciximab - Preliminary Results ACC

23. ADMIRAL 1999, Oral Presentation Major Bleeding Events - Preliminary Results 0.6 1.3 0.7 0.6 1.4 2.0 0 2 4 6 CerebralBlood TransfusionsOther Major % of Patients PlaceboAbciximab ACC

24. ADMIRAL 1999, Oral Presentation Conclusions In patients with acute myocardial infarction, abciximab in conjunction with primary stenting positively improved: –early TIMI 3 flow rate –left ventricular function –30-day clinical results The excess in minor bleeding may be due to the 24-hour arterial sheath ESC