A Prospective, Randomized Comparison of Bivalirudin vs. Heparin Plus Glycoprotein IIb/IIIa Inhibitors During Primary Angioplasty in Acute Myocardial Infarction – 30 Day Results – Gregg W. Stone MD For the HORIZONS AMI Investigators

Disclosures   Gregg W. Stone MD – –Research support from The Medicines Company and Boston Scientific – –Honoraria from Eli Lilly Co.

Background  In addition to suppressing periprocedural ischemia, prevention of hemorrhagic complications has emerged as a priority in patients undergoing PCI  In patients with stable angina and NSTEMI, the direct thrombin inhibitor bivalirudin has been shown to result in similar rates of composite ischemia as heparin plus GP IIb/IIIa inhibitors, while significantly reducing major bleeding  Whether bivalirudin has comparable safety and efficacy in patients with STEMI undergoing primary PCI is unknown

Harmonizing Outcomes with Revascularization and Stents in AMI ≥3400* pts with STEMI with symptom onset ≤12 hours Emergent angiography, followed by triage to… Primary PCI CABG– Medical Rx – UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy (± provisional GP IIb/IIIa) Aspirin, thienopyridine R 1: pts eligible for stent randomization R 1:3 Bare metal stent TAXUS paclitaxel-eluting stent *To rand 3000 stent pts Clinical FU at 30 days, 6 months, 1 year, and then yearly through 5 years Clinical FU at 30 days, 6 months, 1 year, and then yearly through 5 years

Harmonizing Outcomes with Revascularization and Stents in AMI ≥3400* pts with STEMI with symptom onset ≤12 hours UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy (± provisional GP IIb/IIIa) Aspirin, thienopyridine R 1:1 Pharmacology Arm Primary Endpoints* 30 Day Intention to Treat Population * All stent randomization results are still blinded

30 Day Study Objectives  In patients with STEMI undergoing a primary PCI strategy, compared to UFH plus the routine use of GP IIb/IIIa inhibitors, bivalirudin monotherapy will result in: –Similar or reduced rates of net adverse clinical events (the composite of ischemic major adverse cardiovascular events and major bleeding) at 30 days –Similar or reduced rates of major bleeding at 30 days

2 Primary Endpoints (at 30 Days) 1) Net Adverse Clinical Events 2) Major Bleeding (non CABG) Intracranial bleeding intraocular bleeding Retroperitoneal bleeding Access site bleed requiring intervention/surgery Hematoma ≥5 cm Hgb  ≥3g/dL with an overt source Hgb  ≥4g/dL w/o overt source Reoperation for bleeding Blood product transfusion and

2 Primary Endpoints (at 30 Days) 1) Net Adverse Clinical Events 2) Major Bleeding (non CABG) = or All cause death Reinfarction Ischemic TVR Stroke Major adverse cardiovascular events (major secondary endpoint)

Harmonizing Outcomes with Revascularization and Stents in AMI UFH + GP IIb/IIIa N=1802 Bivalirudin Monotherapy N=1800 R 1:1 Randomized 30 day FU* * Range ±7 days ITT population N=1778 (98.7%) N=1777 (98.7%) N=1802N=1800 Withdrew Withdrew Lost to FU Lost to FU pts with STEMI

Primary Management Strategy* UFH + GP IIb/IIIa Inhibitor N=1802 Bivalirudin Monotherapy N=1800 Primary PCI Deferred PCI CABG Medical Rx *Primary ITT analysis includes all pts regardless of treatment

Diff = Diff = 0.0% [-1.6,1.5] RR = 0.99 RR = 0.99 [0.76,1.30] P sup = 1.00 Primary Outcome Measures (ITT) Diff = Diff = -3.3% [-4.0,-1.6] RR = RR = 0.60 [0.46,0.77] P NI ≤ P sup ≤ Diff = Diff = -2.9% [-4.9,-0.8] RR = RR = 0.76 [0.63,0.92] P NI ≤ P sup =  endpoint *Not related to CABG **MACE = All cause death, reinfarction, ischemic TVR or stroke

30 Day MACE Components* UFH + GP IIb/IIIa (N=1802)Bivalirudin(N=1800) P Value Death3.1%2.1% Cardiac - Cardiac2.9%1.8% Non cardiac - Non cardiac0.2%0.3%0.75 Reinfarction1.8%1.8% Q-wave - Q-wave1.2%1.4% Non Q-wave - Non Q-wave0.7%0.4%0.50 Ischemic TVR 1.9%2.6% Ischemic TLR - Ischemic TLR1.8%2.5% Ischemic remote TVR - Ischemic remote TVR0.3%0.3%1.0 Stroke0.6%0.7%0.69 *CEC adjudicated

Conclusions  In this large scale, prospective, randomized trial of pts with STEMI undergoing a primary PCI management strategy, compared to UFH plus the routine use of GP IIb/IIIa inhibitors, bivalirudin monotherapy with GP IIb/IIIa inhibitors reserved for suboptimal PCI outcomes resulted in: –A significant 24% reduction in the 30 day primary endpoint of net adverse clinical events –A significant 40% reduction in the 30 day primary endpoint of major bleeding