Infarct Size after Primary Angioplasty Patients With Bivalirudin Compared to Unfractionated Heparin Plus Abciximab in STEMI: The HORIZONS-AMI MRI Substudy Jochen Wöhrle, Nico Merkle, Thorsten Nusser, Markus Kunze, Eugenia Nikolsky, Akiko Maehara, Alexandra J Lansky, Roxana Mehran, Gregg W Stone

Disclosures Jochen Wöhrle None Nico Merkle None Thorsten Nusser None Markus Kunze None Eugenia Nikolsky None Akiko Maehara None Alexandra J Lansky Grant support: The Medicines Company Roxana Mehran Grant support, Lecture fees: The Medicines Company Gregg W. Stone Advisory Board: Boston Scientific; Abbott

Background Primary PCI is the preferred reperfusion strategy in patients with ST elevation myocardial infarction In the HORIZONS-AMI trial, 3602 pts were randomized to treatment with bivalirudin or unfractionated heparin + glycoprotein IIb/IIIa inhibitor (UFH+GPI). Within 12 months, there was a significant reduction of bleeding events and cardiac death in pts treated with bivalirudin as compared to UFH+GPI (eptifibatide or abciximab).

Background Abciximab has been reported to reduce microvascular obstruction and infarct size in STEMI. Cardiac magnetic resonance imaging (CMRI) is a powerful tool to assess infarct size, microvascular obstruction and left ventricular function and volumes. Whether there are differences in infarct size, LV ejection fraction and volumes determined in CMRI between STEMI patients with primary PCI treated with bivalirudin or UFH+abciximab has not been addressed so far.

Harmonizing Outcomes with Revascularization and Stents in AMI Patients with STEMI with symptom onset ≤12 hours ASA 500mg i.v. Clopidogrel 600mg loading dose R 1:1 Bivalirudin monotherapy (± provisional abciximab) UFH + Abciximab Successful primary PCI with stent implantation CMRI: within 7 days and after 6 months UFH + Abciximab + CMRI N=23 Bivalirudin + CMRI N=28

Baseline Characteristics (i) Bivalirudin (N=28) UFH+Abciximab (N=23) Age (years) 64.3 [60.0, 69.4] 62.4 [54.9, 68.8] Male 60.7% 73.9% Diabetes 14.3% 4.3% Hypertension 67.9% 43.5% Hyperlipidemia 57.1% 56.5% Current smoking 28.6% 39.1% Prior MI 3.6% Prior PCI 0.0% Prior CABG Weight (kg) 81 [75, 91] 80 [70, 86]

Baseline Characteristics (ii) Bivalirudin (N=28) UFH+Abciximab (N=23) Time intervals, min Chest pain – balloon 196 [145, 316] 177 [131, 270] Cath lab – first angio 16 [13-20] 17 [15-22] Target vessel LAD 34.5% 26.1% CX 13.8% 17.4% RCA 48.3% 56.5% SVG 3.4% 0.0% Killip class 2-4 7.1%

TIMI Flow pre and post PCI Bivalirudin (N=28) UFH+Abciximab (N=23) TIMI flow pre PCI - TIMI 0/1 51.7% 65.2% - TIMI 2 31.0% 21.7% - TIMI 3 17.2% 13.0% TIMI flow after PCI 3.4% 0.0% 13.8% 82.8% 100%

Study Drugs and Stents Bivalirudin (N=28) UFH+Abciximab (N=23) UFH pre randomization 100% Antithrombin in CCL - UFH 0%* - Bivalirudin 100%* 0% - Peak ACT 447 [366, 531]** 354 [255, 404] Abciximab any in CCL 7.1%* bailout DES (Taxus) 75.0% 73.9% Express (Express) 25.0% 26.1% Bailout for giant thrombus or refractory no reflow after PCI. CCL = cardiac catheterization laboratory * P<0.001; **P<0.05

Drug therapy Discharge medication Clopidogrel Acetylsalicylic acid % 96.4 100 91.3 25.0 30.4 Beta- blocker ACE/ ARB Statin Diuretics Discharge medication Clopidogrel % 100 95.7 30 days discharge 6 months Acetylsalicylic acid 30 days discharge 6 months % 100 96.4 92.3 95.7

CMRI Baseline Data Bivalirudin (N=28) UFH+Abciximab (N=23) P-Wert Infarct size, % median mean 9.3 [4.9; 26.6] 15.4±13.7 20.0 [5.9; 28.2] 19.8±14.0 0.28 LV-EF, % 53.6 [47.8; 70.7] 58.4±12.4 60.1 [53.7; 67.4] 60.7±8.9 0.42 LV-EDVI, mL/m2 64.5 [57.7; 74.5] 65.5±12.7 66.7 [59.0; 81.9] 69.2±13.6 0.32 LV-ESVI, mL/m2 27.7 [16.6; 39.8] 27.9±11.5 27.4 [18.0; 35.5] 27.9±10.2 0.95 LV-SVI, mL/m2 38.4 [31.3; 43.6] 37.6±8.1 40.5 [34.5; 49.1] 41.3±7.0 0.15 Microvascular obstruction, presence 28.6% 34.8% 0.63

CMRI – Infarct size % p = 0.28 p = 0.73 p = 0.09 15.4 ± 13.7 19.8 ± 14.0 12.1 ± 10.9 12.2 ± 13.9 mean median 9.3 [4.9;26.6] 20.0 [5.9;28.2] 6.7 [3.8;20.0] 8.2 [1.8;16.5] -3.7 [-7.7;0.0] -6.5 [-12.8;-1.9] -4.3 ± 5.1 -8.0 ± 6.9 Baseline 6 months Difference baseline -6 months %

CMRI – LVEF p = 0.42 p = 0.84 p = 0.23 58.4 ± 12.4 60.7 ± 8.9 63.6 ± 11.6 62.2 ± 12.6 mean median 53.6 [47.8;70.7] 60.1 [53.7;67.4] 65.5 [55.4;73.1] 66.7 [54.8;69.6] 4.5 [-0.4;9.9] 0.2 [-4.1;7.7] 5.7 ± 10.1 1.5 ± 9.3 Baseline 6 months Difference baseline -6 months %

CMRI – LVEDVI mL/m² 65.5 ± 12.7 69.2 ± 13.6 73.8 ± 14.1 80.0 ± 23.2 mean median 64.5 [57.7;74.5] 66.7 [59.0;81.9] 70.2 [63.3;81.0] 76.9 [62.0;82.8] p = 0.32 p = 0.40 6.8 [-0.4;14.4] 6.3 [-1.9;26.2] 8.5 ± 10.5 10.3 ± 19.7 p = 1.00 Baseline 6 months Difference baseline -6 months mL/m²

CMRI – LVESVI mL/m² 27.9 ± 11.5 27.9 ± 10.2 27.9 ± 13.6 31.9 ± 20.6 mean median 27.7 [16.6;39.8] 27.4 [18.0;35.5] 25.1 [15.7;32.1] 24.9 [22.6;37.7] p = 0.95 p = 0.54 -0.4 [-3.6;3.7] -0.8 [-5.8;12.3] -0.4 ± 9.6 3.7 ± 16.0 p = 0.84 Baseline 6 months Difference baseline -6 months mL/m²

CMRI – LVSVI mL/m² mL/m² p = 0.76 p = 0.21 p = 0.15 Baseline 6 months Difference baseline -6 months median 38.4 [31.3;43.6] 40.5 [34.5;49.1] 44.4 [40.1;49.8] 45.1 [39.6;55.1] 9.8 [3.6;12.8] 5.8 [-0.5;11.4] mean 37.6 ± 8.1 41.3 ± 7.0 45.9 ± 7.6 48.0 ± 11.3 8.9 ± 8.1 6.4 ± 9.9

Conclusions In the prospective randomized HORIZONS-AMI trial including patients with primary PCI with stent implantation for STEMI, treatment with bivalirudin as compared to UFH+abciximab did not show a difference in CMRI parameters at baseline and at 6 months, including microvascular obstruction, infarct size, LV-EF and LV volumes.