Assessment of the Safety and Efficacy of a New Treatment Strategy for Acute Myocardial Infarction (ASSENT-4 PCI) Trial ASSENT- 4 PCI Trial Presented at The European Society of Cardiology Hot Line Session 2005 Presented by Dr. Frans Van de Werf

www. Clinical trial results.org Full-dose TNK + Primary PCI n=829 GP IIb/IIIa inhibitors allowed only for bail out use Full-dose TNK + Primary PCI n=829 GP IIb/IIIa inhibitors allowed only for bail out use ASSENT- 4 PCI Trial 1667 patients with ST elevation myocardial infarction (summed ST deviation > 6 mm); time from symptom onset within 6 hrs; intent to perform primary PCI Randomized Mean follow-up: 6 mos (30 days reported to date) 63% of patients received clopidogrel/ticlopidine during PCI Additional UFH was given to 67.4% in the TNK + PCI group and 70.1% in the PCI alone group 1667 patients with ST elevation myocardial infarction (summed ST deviation > 6 mm); time from symptom onset within 6 hrs; intent to perform primary PCI Randomized Mean follow-up: 6 mos (30 days reported to date) 63% of patients received clopidogrel/ticlopidine during PCI Additional UFH was given to 67.4% in the TNK + PCI group and 70.1% in the PCI alone group Presented at ESC 2005 Primary PCI n=838 GP IIb/IIIa inhibitors allowed at discretion of physician Primary PCI n=838 GP IIb/IIIa inhibitors allowed at discretion of physician  Primary Endpoint: Composite of death, shock, or congestive heart failure at 90 days.  Secondary Endpoint: Composite of death, shock, or congestive heart failure at 30 days; shock or CHF at 90 days; single components of the composite endpoint.  Primary Endpoint: Composite of death, shock, or congestive heart failure at 90 days.  Secondary Endpoint: Composite of death, shock, or congestive heart failure at 30 days; shock or CHF at 90 days; single components of the composite endpoint.

www. Clinical trial results.org ASSENT- 4 PCI Trial Patients undergoing PCI among two treatment groups (%) p=0.01 GP IIb/IIIa inhibitor administration prior to and during PCI (%) Presented at ESC 2005 PCI was performed at a median of 104 minutes following TNK bolus administration PCI was performed at a median of 104 minutes following TNK bolus administration Median time from symptom onset to randomization was 140 minutes in the combined therapy group and 135 minutes in the PCI alone group Median time from symptom onset to randomization was 140 minutes in the combined therapy group and 135 minutes in the PCI alone group 19% of patients were randomized in the ambulance 19% of patients were randomized in the ambulance p<0.001

www. Clinical trial results.org Presented at ESC 2005 ASSENT- 4 PCI Trial: TIMI Flow Grade TIMI grade 3 flow prior to PCI and TIMI grade 2/3 flow post-PCI (%) p<0.001 TIMI grade 3 flow prior to PCI was present more frequently in the TNK + PCI arm (43.6% vs 15.0%)TIMI grade 3 flow prior to PCI was present more frequently in the TNK + PCI arm (43.6% vs 15.0%) TIMI grade 2/3 post-PCI was slightly higher in the PCI alone group (95.3% vs 97.6%)TIMI grade 2/3 post-PCI was slightly higher in the PCI alone group (95.3% vs 97.6%)

www. Clinical trial results.org Presented at ESC 2005 ASSENT- 4 PCI Trial: Abrupt Closure and Re-infarction Analysis of in-hospital abrupt closure and re- infarction among two treatment groups (%) p<0.001 In-hospital abrupt closure occurred more often in the TNK + PCI treatment group (1.9% vs 0.1%) In-hospital abrupt closure occurred more often in the TNK + PCI treatment group (1.9% vs 0.1%) Re-infarction occurred more often in the TNK + PCI treatment group (4.1% vs 1.9%) Re-infarction occurred more often in the TNK + PCI treatment group (4.1% vs 1.9%) p=0.01

www. Clinical trial results.org ASSENT- 4 PCI Trial: Mortality at 30 days The primary endpoint of mortality was higher in the TNK + PCI treatment group compared with the PCI alone group (6.0% vs 3.8%, p=0.04) at 30 days Analysis of mortality at 30 days (%) p = 0.04 Presented at ESC 2005 n=50 n=32

www. Clinical trial results.org ASSENT- 4 PCI Trial: Mortality Subgroup Analysis The greatest mortality difference by treatment group was seen in hospitals with on- site PCI (7.3% vs 3.8%), with less difference in community hospitals (6.0% vs 4.0%), and a shift in direction for patients enrolled in the ambulance (3.1% vs 3.7%) Subgroup analysis of mortality based on site of randomization (%) Presented at ESC 2005

www. Clinical trial results.org ASSENT- 4 PCI Trial: Stroke and ICH at 30 days Total stroke occurred more often in the TNK + PCI group (1.8% vs 0%), as did ICH (0.97% vs 0%) at 30 days Analysis of total Stroke and ICH at 30 days (%) Presented at ESC 2005 p<0.001 p=0.004

www. Clinical trial results.org ASSENT- 4 PCI Trial: Bleeding Events at 30 days No difference in the frequency of major bleed existed between the two treatment groups (5.7% vs 4.4%) at 30 days The presence of any bleeding event (major + minor bleeding) was more common in the TNK+ PCI treatment group (31.3% vs 23.4%) at 30 days (p<0.001). Analysis of bleeding events at 30 days (%) Presented at ESC 2005 p=0.26 p<0.001

www. Clinical trial results.org ASSENT- 4 PCI Trial: Summary The trial intended to enroll 4,000 patients, but was discontinued early after enrollment of 1,667 patients. Among patients with ST elevation MI intended for primary PCI, administration of full-dose fibrinolytic (TNK) immediately prior to PCI was associated with increased mortality and stroke at 30 days compared with primary PCI alone. Primary endpoint data are not yet available. Further evaluation of the clinical benefit of fibrinolytics among patients undergoing early PCI for STEMI appears warranted (FINESSE). The trial intended to enroll 4,000 patients, but was discontinued early after enrollment of 1,667 patients. Among patients with ST elevation MI intended for primary PCI, administration of full-dose fibrinolytic (TNK) immediately prior to PCI was associated with increased mortality and stroke at 30 days compared with primary PCI alone. Primary endpoint data are not yet available. Further evaluation of the clinical benefit of fibrinolytics among patients undergoing early PCI for STEMI appears warranted (FINESSE). Presented at ESC 2005