1. Presentation at a Non PCI Facility Requiring Transfer Does NOT Worsen Long-term Prognosis in Patients With STEMI Undergoing Primary Angioplasty. The HORIZONS-AMI Trial – One Year Results For the HORIZONS AMI Investigators, Jochen Wöhrle, Bruce R. Brodie, Giulio Guagliumi, Bernhard Witzenbichler, Jan Z. Peruga, Dariusz Dudek, Ran Kornowski, Franz Hartmann, Bernard J. Gersh, Giora Weisz, Helen Parise, Roxana Mehran, Lynn Vandertie, Louise Gambone, Gregg W. Stone

2. Disclosures Jochen WöhrleNone Bruce R. BrodieNone Giulio GuagliumiGrant support: LightLab, Medtronic Vascular, Boston Scientific, Research grant: Boston Scientific Bernhard Witzenbichler None Jan Z. PerugaNone Dariusz Dudek, None Ran KornowskiNone Franz HartmannNone Bernard J. GershNone Giora WeiszNone Helen PariseNone Roxana MehranGrant support, Lecture fees: The Medicines Company Lynn VandertieNone Louise GamboneNone Gregg W. Stone Advisory Board: Boston Scientific; Abbott

3. Background  Primary PCI is the preferred reperfusion strategy in patients with ST elevation myocardial infarction  Need for transfer of patients to a PCI facility for primary PCI is associated with a delay in reperfusion due to time for transfer compared to patients with direct admission to a PCI center.  Long-term clinical outcomes between patients with need for transfer compared to patients without need for transfer for primary PCI were examined in the large-scale, multicenter HORIZONS-AMI trial.

4. Pharmacology Arm One year results Intention to Treat Population UFH + GP IIb/IIIa inhibitor (abciximab or eptifibatide) Bivalirudin monotherapy (± provisional GP IIb/IIIa) Harmonizing Outcomes with Revascularization and Stents in AMI 3602 pts with STEMI with symptom onset ≤12 hours Aspirin, thienopyridine R 1:1

5. Pharmacology Arm One year results Intention to Treat Population With Transfer N=988 Without Transfer N=2614 Harmonizing Outcomes with Revascularization and Stents in AMI 3602 pts with STEMI with symptom onset ≤12 hours

6. Baseline Characteristics (i) First presentation Transfer Hosp. (N=988) PCI Hosp. (N=2614) Age (years) 60.0 [52.3, 70.2] 60.2 [52.4, 69.8] Male75.6%77.0% Diabetes14.3%*17.3% Hypertension52.2%53.9% Hyperlipidemia38.6%*44.8% Current smoking 46.9%45.8% Prior MI 9.1%*11.6% Prior PCI 6.9%*12.2% Prior CABG 2.1%3.2% Weight (kg) 80 [70, 90] 80 [71, 90] * P<0.05

7. Baseline Characteristics (ii) First presentation Transfer Hosp. (N=988) PCI Hosp. (N=2614) Chest pain – ER, min 106 [60, 191] 117 [68, 205] Chest pain – SH, min 196 [135-300]** 117 [68-205] SH – Cath lab, min 31 [14-55]** 52 [33-77] Killip class 2-4 8.2%8.6% Target vessel LAD 39.9%40.9% LVEF 50 [45, 60] 50 [42, 60] Femoral a. access 90.3%*95.0% Venous access 7.6%9.4% Closure device 29.1%29.0% * P<0.05** P<0.0001 SH=Study hospital * P<0.05 ** P<0.0001 SH=Study hospital

8. 92.9% Primary Management Strategy* Transfer Hospital N=988 PCI Hospital N=2614 Primary PCI Deferred PCI CABG Medical Rx *Primary ITT analysis includes all pts regardless of treatment 92.7%

9. Median Time Intervals – PCI Cohort

10. TIMI Flow pre and post PCI First presentation Transfer Hosp. (N=988) PCI Hosp. (N=2614) TIMI flow pre PCI - TIMI 0/1 - TIMI 0/162.3%*66.5% - TIMI 2 - TIMI 217.1%15.5% - TIMI 3 - TIMI 320.6%18.0% TIMI flow after PCI - TIMI 0/1 - TIMI 0/12.1%2.5% - TIMI 2 - TIMI 26.4%6.0% - TIMI 3 - TIMI 391.6%91.5% * P<0.05

11. Study Drugs First presentation Transfer Hosp. (N=988) PCI Hosp. (N=2614) UFH pre randomization 73.2%*62.7% Antithrombin in CCL - UFH - UFH51.6%50.4% - Bivalirudin - Bivalirudin47.5%49.3% - Peak ACT - Peak ACT 310 [246, 380] 307 [250, 388] GP IIb/IIIa any 53.2%54.8% - Bail-out per protocol** - Bail-out per protocol**4.8%*8.6% - Abciximab - Abciximab32.3%*27.2% - Eptifibatide - Eptifibatide20.7%*27.3% - Tirofiban - Tirofiban0.3%0.4% ** For giant thrombus or refractory no reflow after PCI. CCL = cardiac catheterization laboratory * P<0.01

12. Diff = - Diff = -0.4% [-2.8, 1.9] RR = 0.96 RR = 0.96 [0.78, 1.20] P = 0.74 Primary Outcome Measures (ITT) Diff = 0 Diff = 0.5% [-1.5, 2.4] RR = RR = 1.07 [0.82, 1.39] P = 0.63 Diff = - Diff = -0.9% [-3.6, 1.9] RR = RR = 0.95 [0.79, 1.14] P = 0.59 *Not related to CABG **MACE = All cause death, reinfarction, ischemic TVR or stroke 16.3 17.2 7.9 7.4 11.6 12.0 Transfer Hospital (N=988)PCI Hospital (N=2614)

13. One Year Net Adverse Clinical Events 988841817798728 26142216215521111896 Number at risk Transfer PCI Hospital Transfer Hospital (n=988) PCI Hospital (n=2614) NACE (%) 0 2 4 6 8 10 12 14 16 18 20 22 Time in Months 0123456789101112 P (interaction) = 0.31

14. One Year Major Bleeding (non-CABG) 988866855841766 26142297227722592050 Number at risk Transfer PCI Hospital Transfer Hospital (n=988) PCI Hospital (n=2614) Major Bleeding (%) 0 1 2 3 4 5 6 7 8 9 10 11 12 Time in Months 0123456789101112 P (interaction) = 062

15. One Year Bleeding Endpoints Transfer Hosp. (N=988) PCI Hosp. (N=2614) P Value Protocol Major, non CABG 7.9%7.4%0.63 Protocol Major, All 10.6%9.4%0.28 Blood transfusion 3.6%3.2%0.59 TIMI Major 4.9%4.4%0.49 TIMI Minor 4.2%3.8%0.60 TIMI Major or Minor 9.0%8.1%0.39 GUSTO LT* or Severe 0.8%0.7%0.25 GUSTO Moderate 5.3%4.2%0.16 GUSTO LT* or Sev or Mod 5.1%4.4%0.37 *Life threatening

16. One Year Major Adverse CV Events 988893865843768 26142353228722412006 Number at risk Transfer PCI Hospital Transfer Hospital (n=988) PCI Hospital (n=2614) MACE (%) 0 2 4 6 8 10 12 14 16 Time in Months 0123456789101112 P (interaction) = 0.41

17. One Year MACE Components* First presentation Transfer Hosp. (N=988) PCI Hosp. (N=2614) P Value Death4.0%4.2%0.80 - Cardiac - Cardiac2.6%3.1%0.40 - Non cardiac - Non cardiac1.5%1.1%0.39 Reinfarction4.2%3.9%0.68 - Q-wave - Q-wave2.1%2.1%0.93 - Non Q-wave - Non Q-wave2.4%1.9%0.40 Ischemic TVR 6.0%6.7%0.42 - Ischemic TLR - Ischemic TLR5.0%5.3%0.68 - Ischemic remote TVR - Ischemic remote TVR2.3%2.1%0.79 Stroke1.3%1.1%0.47 *CEC adjudicated

18. One Year Stent Thrombosis Transfer Hospital (N=850) PCI Hospital (N=2274)PValue ARC definite or probable*2.8%3.6%0.25 - definite2.6%2.9%0.58 - probable0.2%0.7%0.12 Late (>30d-1<r), def/prob1.1%1.0%0.91 *Protocol definition of stent thrombosis, CEC adjudicated

19. Conclusions  In this large scale, international, prospective, randomized trial of patients with STEMI undergoing a primary PCI management strategy, despite a median treatment delay of 67 minutes, patients requiring transfer for PCI compared to those presenting at a PCI facility resulted in: –Similar one year rates of net adverse clinical events –Similar one year rates of major bleeding –Similar one year rates of major adverse cardiovascular events