The INT egrelin and E noxaparin R andomized assessment of A cute C oronary syndrome Treatment T rial Sponsored by the Canadian Heart Research Centre, Key Pharmaceuticals, Division of Schering Canada Inc. and Millenium Pharmaceuticals Inc. Enoxaparin provided by Aventis Canada As Presented by Shaun G Goodman on behalf of the INTERACT Trial Investigators ACC 2002 The INTERACT Study

INTERACT Preliminary Results The INTERACT Study 746 patients UA/NSTEMI  Chest pain > 10 min within 24 hr  0.5 mm ST Segment depression/ transient elevation  Positive cardiac markers (CK-MB or troponin) 180/2.0 dose eptifibatide for 48 hrs ASA 160 mg initially  mg daily 746 patients UA/NSTEMI  Chest pain > 10 min within 24 hr  0.5 mm ST Segment depression/ transient elevation  Positive cardiac markers (CK-MB or troponin) 180/2.0 dose eptifibatide for 48 hrs ASA 160 mg initially  mg daily Treatment Group A UFH 70 IU/kg bolus/0.15 U/kg- hr (aPTT sec) (n = 366) Treatment Group A UFH 70 IU/kg bolus/0.15 U/kg- hr (aPTT sec) (n = 366) Treatment Group B 1.0 mg/kg q12 enoxaparin (n = 380) Treatment Group B 1.0 mg/kg q12 enoxaparin (n = 380) Endpoints:  Primary - Major/Minor TIMI Bleeding  Secondary - D/MI/recurrent ischemia - ST segment monitoring Endpoints:  Primary - Major/Minor TIMI Bleeding  Secondary - D/MI/recurrent ischemia - ST segment monitoring Goodman et al, ACC 2002

INTERACT Preliminary Results INTERACT: Exclusion Criteria Uninterpretable 12 lead EKG at baseline Recent fibrinolysis or GP IIbIIIa inhibitor therapy Prior administration of unfractionated or low molecular weight heparin within the past 24 hours Administration of unfractionated or low molecular weight heparin for over 12 hours Uninterpretable 12 lead EKG at baseline Recent fibrinolysis or GP IIbIIIa inhibitor therapy Prior administration of unfractionated or low molecular weight heparin within the past 24 hours Administration of unfractionated or low molecular weight heparin for over 12 hours Goodman et al, ACC 2002

INTERACT Preliminary Results INTERACT: Baseline Characteristics Weight (kg) Heart rate (beats/min) Systolic BP (mm Hg) Diastolic BP (mm Hg) Killip Class IIIIII-IV ST Deviation  0.1 mV,  2 leads Index Infarction (Marker +) UFH(n=366) 79 (68, 89) 72 (63, 82) 134 (120, 150) 77 (68, 87) Enoxaparin(n=380) 79 (70, 92) 70 (60, 81) 134 (120, 151) 77 (66, 87) Goodman et al, ACC 2002

INTERACT Preliminary Results MedicationsMedications ASA (%) Clopidogrel (%) IV Beta Blocker Oral Beta Blocker Calcium Blocker IV Nitrate Oral Nitrate ACE Inhibitor Lipid Lowering UFH(n=366) Enoxaparin(n=380) Goodman et al, ACC 2002

INTERACT Preliminary Results Study Drug Administration Pre-study Heparin (%) Time from symptom onset Eptifibatide duration (hrs) Study drug duration  48 hrs UFH(n=366)    13.4 Enoxaparin(n=380)    20.1 Preliminary Results Goodman et al, ACC 2002

INTERACT Preliminary Results Activated Partial Thromboplastin Time (aPTT) aPTT  12 hrs Sub-therapeutic (<1.5x) Therapeutic (1.5-2x) Supra-therapeutic (>2x) aPTT >12-24 hrs Sub-therapeutic (<1.5x) Therapeutic (1.5-2x) Supra-therapeutic (>2x) aPTT value  12 hrs aPTT value >12-24hrs UFH(n=366)(n=342) (n=330) (61, 148) 67 (54, 90) Preliminary Results Goodman et al, ACC 2002

INTERACT Preliminary Results 30-Day Coronary Angiography and Revascularization Angiography (%) Time to angio (hrs) PCI (%) Time to PCI (hrs) CABG (%) Time to CABG (hrs) UFH(n=365) (60, 168) (60, 232) (207, 470) Enoxaparin(n=379) (65, 164) (76, 335) (160, 460) Goodman et al, ACC 2002

INTERACT Preliminary Results Non-CABG Bleeding Major Minor P=0.084 TIMI Scale 1 P=0.37 GUSTO Scale P= Hct  15% or Hgb  50 g/L 0 0 P= Severe Moderate Mild (Lytic and GP IIb/IIIa Inhibitor trials) Goodman et al, ACC 2002

INTERACT Preliminary Results UFH Enoxaparin P=0.083 All 30-Day Major Bleeding UFH Enoxaparin P=0.079 Non-CABG Related TIMI Scale (LMWH trials) Goodman et al, ACC 2002

INTERACT Preliminary Results UFH Enoxaparin P=0.03 P=0.014 Major Bleeds – 96 Hours Major Bleeds – 48 Hours P=0.024 MInor Bleeds – 96 Hours INTERACT: Non-CABG Bleeding Results Using TIMI Criteria UFH Enoxaparin UFH Enoxaparin Goodman et al, ACC 2002

INTERACT Preliminary Results UFH Enoxaparin P= Hours INTERACT: Ischemic Events by ST Segment Monitoring During the First 96 hours UFH Enoxaparin P= Hours Goodman et al, ACC 2002 n=346 n=357 n=320 n=322

INTERACT Preliminary Results UFH Enoxaparin P=0.031 P=0.30 Death / MI Death / MI / Recurrent Ischemia Death / MI / Recurrent Ischemia P=0.064 INTERACT: 30 Day Events UFH Enoxaparin UFH Enoxaparin Death / MI / Re-Ischemia with ECG Change Death / MI / Re-Ischemia with ECG Change Goodman et al, ACC 2002 n=366 n=380

INTERACT Preliminary Results INTERACT: Summary Compared to a regimen of Eptifibatide and Unfractionated Heparin, Eptifibatide and Enoxaparin is associated with –Lower rates of major hemorrhage –Higher rates of minor hemorrhage –Lower rates of death or recurrent MI –Lower rates of ischemia during and immediately following treatment Compared to a regimen of Eptifibatide and Unfractionated Heparin, Eptifibatide and Enoxaparin is associated with –Lower rates of major hemorrhage –Higher rates of minor hemorrhage –Lower rates of death or recurrent MI –Lower rates of ischemia during and immediately following treatment Goodman et al, ACC 2002

INTERACT Preliminary Results LimitationsLimitations This was open-label study, but endpoints were adjudicated in a blinded fashion as was the continuous ECG monitoring The time to coronary angiography/ revascularization (median 110 hours) was longer than that in TACTICS TIMI 18 where the median time to catheterization was 21 hours This was open-label study, but endpoints were adjudicated in a blinded fashion as was the continuous ECG monitoring The time to coronary angiography/ revascularization (median 110 hours) was longer than that in TACTICS TIMI 18 where the median time to catheterization was 21 hours Goodman et al, ACC 2002

INTERACT Preliminary Results ConclusionsConclusions Among patients treated with eptifibatide in the setting of high risk non-ST elevation ACS, administration of enoxaparin is associated with improves outcomes compared to currently recommended therapy (UF Heparin) based on better safety and efficacy Goodman et al, ACC 2002