1. The HORIZONS-AMI Trial
One Year Outcomes of Primary Angioplasty in Acute Anterior Myocardial Infarction with Bivalirudin Compared to Unfractionated Heparin plus GP IIb/IIIa Inhibitors:
The HORIZONS-AMI Trial
For the HORIZONS AMI Investigators
Jochen Wöhrle, Bernhard Witzenbichler, Giulio Guagliumi, Bruce R. Brodie, Dariusz Dudek, Ran Kornowski,
Franz Hartmann, Helen Parise, Alexandra J. Lansky,
Roxana Mehran, Brendon Ryan, Alison Kellock,
Carol Moore, Gregg W. Stone

2. Disclosures Jochen Wöhrle None Bernhard Witzenbichler None
Giulio Guagliumi Grant support: LightLab, Medtronic Vasc., Boston Scientific; Research grant: Boston Scientific
Bruce R. Brodie None
Dariusz Dudek None
Ran Kornowski None
Franz Hartmann None
Helen Parise None
Alexandra J. Lansky Grant support: The Medicines Company
Roxana Mehran Grant support and Lecture Fees: The Medicines Company
Brendon Ryan None
Alison Kellock None
Carol Moore None
Gregg W. Stone Advisory Board: Boston Scientific; Abbott

3. Background
STEMI patients undergoing primary PCI of LAD compared to non-LAD lesions have a higher rate of major adverse cardiac events.
In the HORIZONS-AMI trial, including STEMI patients undergoing primary PCI, randomization to bivalirudin compared to UFH + GPI resulted in a significant reduction of major bleeding; non significantly different rates of reinfarction, stent thrombosis, stroke and TVR; and significant reduction of all-cause and cardiac mortality at 1 year.
Whether these benefits are also present in STEMI patients with primary PCI of LAD, is unknown.

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

5. Harmonizing Outcomes with Revascularization and Stents in AMI
3602 pts with STEMI with symptom onset ≤12 hours
Aspirin, thienopyridine R
1:1
UFH + GP IIb/IIIa inhibitor
(abciximab or eptifibatide)
Bivalirudin monotherapy
(± provisional GP IIb/IIIa)
PCI cohort:
LAD pts
Non-LAD pts

6. Baseline Characteristics
LAD
(N=1445)
Non-LAD
(N=1884)
Age (years)
61.0 [53.0, 70.7]*
59.5 [52.1, 68.8]
Male
77.9%
76.6%
Diabetes
17.3%
15.5%
Hypertension
52.1%
52.8%
Hyperlipidemia
41.4%
44.0%
Current smoking
42.1%*
50.9%
Prior MI
8.1%*
12.3%
Prior PCI
9.0%*
11.6%
Prior CABG
1.3%
3.5%
Weight (kg)
80 [70, 90]*
80 [71, 91]
* P<0.05

7. Study Drugs LAD (N=1445) Non-LAD (N=1884) UFH pre randomization 64.9%
66.1%
Antithrombin in CCL
- UFH
52.6%
49.5%
- Bivalirudin
47.8%*
51.4%
- Peak ACT
306 [251, 384]
317 [253, 391]
GP IIb/IIIa any
54.0%
51.3%
- Bail-out per protocol**
8.2%
- Abciximab
27.6%
28.5%
- Eptifibatide
26.3%*
22.7%
- Tirofiban
0.1%
0.2%
** For giant thrombus or refractory no reflow after PCI.
CCL = cardiac catheterization laboratory
* P<0.05

8. Primary Outcome Measures (ITT)
LAD (N=1445)
Non-LAD (N=1884)
Diff = 3.9% [1.2, 6.5]
RR = 1.27 [1.08, 1.50]
P = 0.004
Diff = 1.1% [-0.8, 2.9]
RR = 1.15 [0.90, 1.47]
P = 0.27
Diff = 3.8% [1.6, 6.1]
RR = 1.40 [1.15, 1.71]
P =
19.3
15.4
14.1
10.3
8.4
7.3
*Not related to CABG
**MACE = All cause death, reinfarction, ischemic TVR or stroke

9. One Year Bleeding Endpoints
LAD
(N=1445)
Non-LAD
(N=1884)
P Value
Protocol Major, non CABG
8.4%
7.3%
0.27
Protocol Major, All
9.4%
8.8%
0.60
Blood transfusion
3.7%
3.2%
0.50
TIMI Major
3.9%
3.7%
0.80
TIMI Minor
3.9%
3.9%
0.99
TIMI Major or Minor
7.7%
7.5%
0.88
GUSTO LT* or Severe
1.0%
0.5%
0.09
GUSTO Moderate
3.7%
4.1%
0.54
GUSTO LT* or Sev or Mod
5.1%
4.7%
0.66
*Life threatening

10. One Year MACE Components*
LAD
(N=1445)
Non-LAD
(N=1884)
P Value
Death
5.6%
2.8%
0.0001
- Cardiac
4.2%
1.9%
- Non cardiac
1.5%
0.9%
0.13
Reinfarction
4.5%
3.7%
0.25
- Q-wave
2.0%
2.3%
0.59
- Non Q-wave
2.6%
1.6%
0.04
Ischemic TVR
7.7%
6.2%
0.09
- Ischemic TLR
6.3%
4.9%
0.10
- Ischemic remote TVR
2.5%
2.2%
0.53
Stroke
1.0%
0.89
*CEC adjudicated

11. One Year Stent Thrombosis
LAD
(N=1445)
Non-LAD
(N=1884) P
Value
ARC definite or probable*
3.4%
0.95
- definite
2.8%
2.9%
0.86
- probable
0.7%
0.5%
0.58
Late (>30d-1<r), def/prob
1.1%
1.0%
0.97
*Protocol definition of stent thrombosis, CEC adjudicated

12. Harmonizing Outcomes with Revascularization and Stents in AMI
1445 pts with STEMI and primary PCI of LAD
UFH + GP IIb/IIIa inhibitor
(abciximab or eptifibatide)
N=746
Bivalirudin monotherapy
(± provisional GP IIb/IIIa)
N=699
Pharmacology Arm
One year results
Intention to Treat Population

13. Baseline Characteristics (i)
Bivalirudin
(N=699)
UFH+GP IIb/IIIa
(N=746)
Age (years)
60.7 [52.4, 70.8]
61.1 [53.0, 70.7]
Male
77.4%
78.3%
Diabetes
16.2%
18.4%
Hypertension
51.1%
53.1%
Hyperlipidemia
41.5%
40.3%
Current smoking
44.5%
39.8%
Prior MI
8.3%
7.9%
Prior PCI
9.6%
8.5%
Prior CABG
1.6%
1.1%
Weight (kg)
80 [70, 90]
* P<0.05

14. Baseline Characteristics (ii)
Bivalirudin
(N=699)
UFH+GP IIb/IIIa
(N=746)
Chest pain – balloon
221 [165, 337]
220 [160, 346]
Chest pain – SH, min
129 [75, 240]
120 [75, 235]
SH – Cath lab, min
47 [30, 72]
46 [28, 70]
Killip class 2-4
12.9%
12.8%
LVEF
45 [38, 55]
45 [37, 52]
Femoral a. access
93.3%
93.8%
Venous access
6.7%
4.4%
Aspiration catheter
9.5%
8.8%
Closure device
27.5%
28.0%

15. TIMI Flow pre and post PCI
Bivalirudin
(N=699)
UFH+GP IIb/IIIa
(N=746)
TIMI flow pre PCI
- TIMI 0/1
60.6%
61.1%
- TIMI 2
18.6%
18.2%
- TIMI 3
20.9%
20.7%
TIMI flow after PCI
2.3%
1.9%
7.4%
6.8%
90.3%
91.3%

16. Study Drugs Bivalirudin (N=699) UFH+GP IIb/IIIa (N=746)
UFH pre randomization
66.8%
63.2%
Antithrombin in CCL
- UFH
2.1%*
99.9%
- Bivalirudin
98.4%*
0.0%
- Peak ACT
360 [300, 407]*
265 [229, 317]
GP IIb/IIIa any in CCL
7.5%*
97.6%
- Bail-out per protocol**
8.2%
---
- Abciximab
4.4%*
49.2%
- Eptifibatide
3.0%*
48.1%
- Tirofiban
0.3%
** For giant thrombus or refractory no reflow after PCI.
CCL = cardiac catheterization laboratory
* P<0.01

17. Primary Outcome Measures (ITT)
UFH+GP IIb/IIIa (N=746)
Bivalirudin (N=699)
Diff = -2.0% [-6.0, 2.1]
RR = 0.89 [0.70, 1.12]
P = 0.31
Diff = -3.6% [-6.5, -0.7]
RR = 0.63 [0.43, 0.91]
P = 0.01
Diff = -0.2% [-3.8, 3.4]
RR = 0.98 [0.75, 1.29]
P = 0.90
20.2
18.3
14.2
14.0
10.1
6.5
*Not related to CABG
**MACE = All cause death, reinfarction, ischemic TVR or stroke

18. One Year Net Adverse Clinical Events Bivalirudin Alone (n=699)
UFH+GP IIb/IIIa (n=746) 22
Bivalirudin Alone (n=699) 20 18 16 14
NACE (%) 12 10 8 6
P (interaction) = 0.40 4 2 1 2 3 4 5 6 7 8 9 10 11 12
Time in Months
Number at risk
UFH+GPI
746
623
605
588
528
Bivalirudin
699
607
589
576
519

19. One Year Major Bleeding (non-CABG) Bivalirudin Alone (n=699)
UFH+GP IIb/IIIa (n=746) 12
Bivalirudin Alone (n=699) 11 10 9 8 7
Major Bleeding (%) 6 5 4
P (interaction) = 0.77 3 2 1 1 2 3 4 5 6 7 8 9 10 11 12
Time in Months
Number at risk
UFH+GPI
746
641
637
631
567
Bivalirudin
699
634
629
624
567

20. One Year Major Adverse CV Events Bivalirudin Alone (n=699)
UFH+GP IIb/IIIa (n=746) 16
Bivalirudin Alone (n=699) 14 12 10
MACE (%) 8 6
P (interaction) = 0.84 4 2 1 2 3 4 5 6 7 8 9 10 11 12
Time in Months
Number at risk
UFH+GPI
746
673
652
634
570
Bivalirudin
699
638
620
606
546

21. One Year Bleeding Endpoints
Bivalirudin
(N=699)
UFH+GP IIb/IIIa
(N=746)
P Value
Protocol Major, non CABG
6.5%
10.1%
0.01
Protocol Major, All
7.4%
11.2%
0.01
Blood transfusion
2.6%
4.6%
0.04
TIMI Major
3.1%
4.8%
0.10
TIMI Minor
2.9%
4.7%
0.07
TIMI Major or Minor
6.0%
9.3%
0.02
GUSTO LT* or Severe
1.3%
0.7%
0.24
GUSTO Moderate
2.5%
4.7%
0.02
GUSTO LT* or Sev or Mod
3.8%
5.4%
0.13
*LT=Life threatening

22. One Year MACE Components*
Bivalirudin
(N=699)
UFH+GP IIb/IIIa
(N=746)
P Value
Death
4.8%
6.3%
0.19
- Cardiac
3.0%
5.3%
0.04
- Non cardiac
1.8%
1.1%
0.32
Reinfarction
3.7%
0.15
- Q-wave
2.0%
1.9%
0.87
- Non Q-wave
1.6%
3.6%
0.03
Ischemic TVR
8.5%
7.1%
- Ischemic TLR
6.8%
5.8%
0.41
- Ischemic remote TVR
2.8%
2.1%
Stroke
1.0%
0.8%
0.71
*CEC adjudicated

23. One Year Stent Thrombosis
Bivalirudin
(N=699)
UFH+GP IIb/IIIa
(N=746) P
Value
ARC definite or probable*
3.3%
3.6%
0.81
- definite
3.0%
2.6%
0.62
- probable
0.3%
1.0%
0.11
Late (>30d-1<r), def/prob
1.1%
0.96
*Protocol definition of stent thrombosis, CEC adjudicated

24. Conclusions (i)
In this large scale, prospective, randomized trial of pts with STEMI undergoing a primary PCI management strategy, analysis of patients with primary PCI of LAD compared to patients with primary PCI of non-LAD resulted at one year in:
Significantly higher rates of net adverse clinical events and major adverse cardiovascular events
Significantly higher rates of all-cause and cardiac mortality
No difference in rate of stent thrombosis
Similar rate of major bleeding

25. Conclusions (ii)
In patients undergoing primary PCI of LAD lesions, anticoagulation with bivalirudin monotherapy as compared to UFH + GP IIb/IIIa inhibitor resulted in
Similar rates of net adverse clinical events, major adverse cardiac events and stent thrombosis
Significantly lower rates of major bleeding and cardiac death