1. Meta Analysis of Primary PCI trials Andreas Baumbach*, Harold Dauerman, Bernardo Cortese, Martial Hamon, Jayne Prats, Efthymios Deliargyris, Roxana Mehran, and Gregg W. Stone Can the Rate of Acute Stent Thrombosis with Bivalirudin Anticoagulation During Primary PCI in STEMI be Reduced with Modified Pharmacologic Regimens? TCT 2012 JACC 2012;60(17SupplB):B219

2. Background ● In the HORIZONS-AMI (HZN) trial, among STEMI patients undergoing primary PCI after aspirin and clopidogrel loading, anticoagulation with bivalirudin (BIV) terminated at the end of the PCI procedure reduced major bleeding, thrombocytopenia and mortality compared to UFH plus a GP IIb/IIIa inhibitor, albeit with an increased risk of acute (≤24 hours) stent thrombosis (AST). ● Whether more potent antiplatelet agents and/or a prolonged BIV infusion may safely reduce this acute stent thrombosis risk is unknown 2 Baumbach A. TCT 2012 JACC 2012;60(17SupplB):B219

3. Methods ●Five contemporary STEMI registries and randomized clinical trials (Post-HZN-5 group) with a total of 1993 patients were identified ●Baseline and treatment characteristics together with 30-day outcomes were evaluated and compared with the HORIZONS-AMI (HZN) trial ●The analysis focused on acute stent thrombosis (AST) rates and major bleeding, as well as rates of treatment strategies alternative to that used in HORiZONS, such as the use of a prolonged bivalirudin (BIV) infusion for 2-4 hours post PCI and/or an oral fast-acting P2Y 12 inhibitor (prasugrel). Baumbach A. TCT 2012 JACC 2012;60(17SupplB):B219

4. Included Studies ● Infuse-AMI: Randomised comparison of i.c. abciximab vs. Bivalirudin only. Bivalirudin arm included (Stone et al. JAMA 2012;307:1817-26) ● PROBI VIRI-2: 3 armed comparison of heparin/abciximab vs. periprocedural Bivalirudin vs. prolonged (4hrs) Bivalirudin (Cortese et al. Am J Cardiol 2011;108:1220-4) ● UVM-Registry: University of Vermont Registry Data (Mueller et al Am J Cardiol 2012; epub august) ● Bristol Registry: Consecutive patients treated with Prasugrel and periprocedural Bivalirudin (Baumbach et al. Int J Cardiol 2011;153(2):222-4) ● EUROVISION: prospective European multicentre registry on bivalirudin use (Data on file, The Medicines Company) 4 Baumbach A. TCT 2012 JACC 2012;60(17SupplB):B219

5. Meta-analysis results 5 StudyTotal N PrasugrelPre Heparin Prolonged Bivalirudin >2hrs Major Bleeding AST INFUSE-AMI452125 (27.7%)287 (63.5%)0%19 (4.2%)0 (0%) PROBI VIRI 21720 (0%) 86 (50%)0 (0%) UVM-Registry34636 (10.4%)207 (59.8%)283(81.8%)15 (4.3%)3 (0.9%) Bristol-Registry345345 (100%)7 (2.0%)0%5 (1.4%)0 (0%) EUROVISION67887 (12.8%)300 (44.2%)413 (62.2%)10 (1.5 %)0 (0%) Combined1993593 (29.8%)801(40.2%)782 (39.2%)49 (2.4%)0.15% HORIZONS-AMI15710%65.4%0%5.1%1.3% Stone GW et al.JAMA 2012 2;307(17):1817-26) Cortese et al Am J Cardiol 2011;108:1220-4) UVM-Registry: Am J Cardiol 2012; epub august) Bristol Registry: Int J Cardiol 2011; 153(2):222-4) EUROVISION: Data on file, The Medicines Company Baumbach A. TCT 2012 JACC 2012;60(17SupplB):B219

6. Conclusions ● Among patients with STEMI undergoing primary PCI with BIV anticoagulation, ● Use of faster and more potent P2Y 12 inhibitors and/or a prolonged BIV infusion may reduce the rate of acute stent thrombosis compared to an abbreviated procedural-only BIV regimen in combination with clopidogrel. ● Randomized studies are warranted to determine whether these strategies improve clinical outcomes without adversely affecting the safety profile of the currently recommended abbreviated bivalirudin infusion 6