1. 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

2. 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

3. 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).

4. 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.

5. 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

6. 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]

7. 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%

8. 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%

9. 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

10. 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

11. 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

12. 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 %

13. 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 %

14. 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

15. 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

16. 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

17. 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.