1. GP IIb/IIIa Inhibition in STEMI: Growing Clinical Trial Evidence

2. VBWG Antman EM et al. Circulation. 2004;110:588-636. Modified from Keeley EC et al. Lancet. 2003;361:13-20. Meta-analysis of 23 trials; N = 7739 PCIFibrinolysis Frequency (%) Death no SHOCK data Recur ischemia Total stroke Hem stroke Major bleed Death, MI, stroke 0 5 10 15 20 25 DeathReMI PCI vs fibrinolysis in STEMI patients: Short-term clinical outcomes

3. VBWG Antman EM et al. Circulation. 2004;110:588-636. Modified from Keeley EC et al. Lancet. 2003;361:13-20. Meta-analysis of 23 trials PCIFibrinolysis Frequency (%) Death, no SHOCK data Recur MI Recur ischemia Death MI stroke Death 0 5 10 15 20 25 30 35 PCI vs fibrinolysis in STEMI patients: Long-term clinical outcomes

4. VBWG ACC/AHA STEMI guidelines: Assessing reperfusion options FibrinolysisPrimary PCI Early presentation (≤3 hours from symptom onset) Invasive strategy not an option Delay to invasive strategy –Door-to-balloon exceeds door-to- needle time by >1 hour –>90 minutes to balloon time High-volume lab with surgical backup High risk from STEMI Fibrinolysis contraindicated (excessive bleeding/ICH) Late presentation –Symptoms >3 hours prior STEMI diagnosis in doubt ICH = intracranial hemorrhageAntman EM et al. Circulation. 2004;109:2480-6.

5. VBWG Chesebro JH et al. Circulation. 1987;76:142-54. TIMI 0 Complete occlusion TIMI 1 Penetration of obstruction by contrast but no distal perfusion TIMI 2 Perfusion of entire artery but delayed flow TIMI 3 Full perfusion, normal flow Mortality is reduced with better flow TIMI flow grade

6. VBWG Nallamothu BK, Bates ER. Am J Cardiol. 2003;92:824-6. Meta-regression analysis of 21 trials Absolute risk difference in death (%) Circle sizes reflect study sample size Solid line = weighted meta-regression P = 0.006 62 minutes Benefit: Favors PCI Harm: Favors lytics PCI-related time delay (minutes) –5 0 5 10 15 020406080100 Mortality benefit of primary PCI declines with PCI-related time delay

7. VBWG Beygui F, Montalescot G. Eur Heart J. 2005;7(suppl):110-4. Major considerations for pharmacologic approaches to facilitate primary PCI Delay between presentation with STEMI and primary PCI vs progressive nature of ischemia-related necrosis Inverse relationship between time-to-reperfusion and extent of salvaged myocardium and survival Relationship between restoration of coronary flow and recovery of contractility and survival after STEMI Facilitated PCI strategy utilizing GP IIb/IIIa inhibition or fibrinolytic therapy provides a degree of coronary reperfusion when PCI is not immediately available

8. VBWG Zeymer U et al. Eur Heart J. 2005;26:1971-7. Patency (%) 0 10 20 50 60 70 80 TIMI 3 30 40 34.0 10.2 TIMI 2 7.6 22.4 TIMI 0/1 58.4 67.4 P = 0.01 Early administration (n = 53) Late or no administration (n = 49) INTegrilin in Acute Myocardial Infarction INTAMI pilot trial: Early eptifibatide improves TIMI 3 flow before PCI for STEMI

9. VBWG Zeymer U et al. Eur Heart J. 2005;26:1971-7. www.timi.org EarlyLate or no GP IIb/IIIa inhibitor 0 10 20 30 40 ZormanReo- Mobile ERAMIReoPro- bridging ADMIRALCutli p TIGER- PA On- TIME INTAMI TIMI 3 patency before PCI (%) N = 109100695530060100487102 316 AbciximabTirofiban TITAN Eptifibatide TIMI 3 patency before PCI in trials of early vs late/no GP IIb/IIIa inhibitors in STEMI

10. VBWG GP IIb/IIIa inhibitors for primary PCI Brener SH et al. Circulation. 1998;98:734-41. Neumann FJ et al. J Am Coll Cardiol. 2000;35:915-21. Montalescot G et al. N Engl J Med. 2001;344:1895-1903. Antoniucci D et al. J Am Coll Cardiol. 2003;42:1879-85. 30-day death, recurrent MI, or urgent revascularization *Outcome also includes stroke 11.2 5.8 10.5 5 14.6 6 10.5 4.5 0 2 4 6 8 10 12 14 16 RAPPORTISAR-2ADMIRAL*ACE P = 0.02 P = 0.01 N = P = 0.04 P = 0.03 % Placebo GP IIb/IIIa inhibitor 483401300400

11. VBWG Beygui F, Montalescot G. Eur Heart J Suppl. 2005;7(suppl I):I10-4. Facilitated PCI in STEMI Early administration of GP IIb/IIIa inhibitors is associated with significant flow restoration, potentially better myocardial reperfusion, and no significant increase in major bleeding Early GP IIb/IIIa facilitation strategy may be recommended in STEMI patients who are candidates for primary PCI Benefits of GP IIb/IIIa therapy in primary PCI for STEMI demonstrated in large clinical trials include improvement in pre-PCI coronary flow, angiographic parameters, and ischemic outcomes and mortality More data from large-scale clinical trials are needed to determine the risks and benefits of facilitated PCI with GP IIb/IIIa inhibitors + fibrinolytics