1. Bivalirudin SCAI-ACC/i2 2008 presentations
HORIZONS AMI subgroups:
Impact of clopidogrel Dangas et al
Diabetes Witzenbichler et al
Renal impairment Mehran et al
Gender Grinfeld et al
Age Dudek et al
Abciximab, eptifibatide strata Gualiumi et al
US, non-US Brodie et al

2. Impact of clopidogrel loading dose on the safety and effectiveness of bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction: The HORIZONS AMI trial
George Dangas, Giulio Guagliumi, Bernhard Witzenbichler, Deepak Bhatt, Frederick Feit, Magnus Ohman, S. Chiu Wong, Helen Parise, Roxana Mehran, Gregg W. Stone

3. Background
In the HORIZONS AMI trial, in pts undergoing primary PCI. bivalirudin monotherapy (Biv) compared to UFH plus GP IIb/IIIa inhibitors resulted in:
– Reduced 30 day rates of major bleeding,
– Comparable composite major adverse cardiovascular events (MACE)
– Enhanced freedom from net adverse clinical events (NACE).
All pts were to receive a clopidogrel loading dose in the ER, either 300 mg or 600 mg, and randomization was stratified by this decision.
Whether the beneficial effects of Biv are independent of the clopidogrel loading dose has not been reported.

4. Baseline Characteristics
300mg LD
600mg LD
P value
Age
60.5 [52.9, 70.5]
60.1 [52.2, 69.3]
0.14
Male
75.5%
76.9%
0.39
Diabetes
17.6%
15.6%
0.13
Insulin
3.7%
4.5%
0.27
Hypertension
51.9%
52.7%
0.63
Hyperlipidemia
41.5%
42.4%
0.62
Current smoking
43.4%
47.4%
0.03
Anemia
9.4%
10.7%
0.25
Platelet count (x103 cells/mm3)
250.5 [210.0, 299.0]
245.0 [207.0, 287.0]
0.02
Renal insufficiency
2.9%
3.1%
0.86
Prior MI
9.6%
9.8%
0.89
Prior PCI
8.5%
Prior CABG
2.3%
0.26
History of PVD
3.9%
0.46
History of CHF
US stratification
30.6%
16.8%
<.0001
Dangas et al, SCAI-ACCi2 2008

5. Baseline Characteristics
300mg LD
600mg LD
P value
Weight (kg)
80.0
[71.0, 90.0]
[71.0, 90.7]
0.17
BMI (kg/m2)
27.1
[24.6, 30.1]
27.0
[24.5, 30.3]
0.50
Chest pain to ER (hours)
2.2
[1.3, 4.0]
[1.3, 3.8]
0.45
KILLIP Class 2-4
11.5%
6.9%
<.0001
LVEF <40%
15.1%
13.7%
0.28
Femoral a. access
87.3%
96.7%
Radial a. access
12.4%
2.9%
Venous access
10.1%
8.0%
0.03
Closure Device
20.3%
33.2%
Peak ACT (sec)
299.0
[244.0, 379.0]
316.0
[254.0, 392.0]
IABP
6.5%
4.8%
0.0353
Dangas et al, SCAI-ACCi2 2008

6. Drug Administration 300mg LD 600mg LD P- value HEPARIN
Pre-Randomization Heparin
60.7%
68.7%
<.0001
Pre-Procedure Heparin
67.9%
72.9%
0.002
Heparin in cath lab, as anticoagulant
51.4%
50.0%
0.43
BIVALIRUDIN
Bivalirudin in cath lab, as anticoagulant
48.4%
0.38
GP IIb/IIIa
In the ER
3.2%
7.5%
In the cath lab, before sheath insertion
11.5%
12.3%
0.50
In the cath lab, Any
52.0%
50.5%
0.42
ANY
55.2%
54.1%
0.54
Dangas et al, SCAI-ACCi2 2008

7. Procedural characteristics (PCI)
300mg LD
600mg LD
P- value
Treated vessels
LAD
41.9%
40.3%
0.38
LCX
15.5%
15.8%
0.80
RCA
40.6%
42.6%
0.28 LM
0.7%
0.5%
0.41
SVG
1.2%
0.8%
0.24
LIMA/ RIMA
0.1%
0.0%
0.35
Door to Balloon (hours)
1.8 [1.3, 2.3]
1.6 [1.2, 2.2]
<.0001
One or more stents implanted
95.6%
96.3%
0.31
Multiple vessels treated
4.5%
4.1%
0.68
Multiple lesions treated
9.9%
11.3%
0.26
Dangas et al, SCAI-ACCi2 2008

8. Procedural characteristics (PCI)
300mg LD
600mg LD
P- value
TIMI flow pre PCI
TIMI 0/1
65.6%
65.2%
0.83
TIMI 2
15.5%
16.2%
0.58
TIMI 3
19.0%
18.6%
0.80
Final TIMI flow after PCI
2.5%
1.8%
0.16
5.0%
6.8%
0.048
92.5%
91.5%
0.31
Dangas et al, SCAI-ACCi2 2008

9. Overall: Primary Outcomes (ITT)
*NACE = MACE or major bleeding
**Not related to CABG
***MACE = All cause death, reinfarction, ischemic TVR or stroke
Dangas et al, SCAI-ACCi2 2008

10. Primary Outcomes (ITT)
The impact of Biv was independent of the dose of clopidogrel loading. Interaction P values for the above 3 endpoints = (NACE) 0.41 (Major bleeding), and 0.75 (MACE).
300 mg LD
600 mg LD
P=0.15
P=0.01
P=0.56
P=0.01
P=0.002
P=0.71
Dangas et al, SCAI-ACCi2 2008

11. Overall: 30 Day MACE Components*
300 mg LD
600 mg LD
P-value
Death
3.1%
1.9%
0.03
- Cardiac
2.7%
0.11
- Non cardiac
0.4%
0.1%
0.054
Reinfarction
2.4%
1.3%
0.02
- Q-wave
1.5%
1.1%
0.37
- Non Q-wave
1.0%
0.3%
Ischemic TVR
2.8%
2.0%
0.15
- Ischemic TLR
2.6%
1.8%
0.13
- Ischemic remote TVR
0.76
Stroke
0.058
*CEC adjudicated
Dangas et al, SCAI-ACCi2 2008

12. BIV group: 30 Day MACE Components*
300 mg LD
600 mg LD
P-value
Death
2.6%
1.4%
0.06
- Cardiac
2.1%
1.3%
0.19
- Non cardiac
0.5%
0.1%
0.11
Reinfarction
2.8%
0.02
- Q-wave
1.8%
1.1%
0.26
- Non Q-wave
0.2%
Ischemic TVR
3.3%
2.3%
0.20
- Ischemic TLR
0.13
- Ischemic remote TVR
0.0%
1.00
Stroke
0.9%
0.6%
0.56
*CEC adjudicated
Dangas et al, SCAI-ACCi2 2008

13. Overall: 30 Day Stent Thrombosis
300 mg LD
600 mg LD
P-value
ARC definite or probable*
2.8%
1.7%
0.04
- definite
2.1%
1.3%
0.11
- probable
0.7%
0.4%
0.20
- acute (≤24 hrs)
1.00
- subacute (>24 hrs – 30d)
2.2%
1.0%
0.008
*Protocol definition of stent thrombosis, CEC adjudicated
Dangas et al, SCAI-ACCi2 2008

14. BIV group: 30 Day Stent Thrombosis
300 mg LD
600 mg LD
P-value
ARC definite or probable*
3.5%
1.7%
0.03
- definite
3.1%
1.5%
0.04
- probable
0.4%
0.2%
0.61
- acute (≤24 hrs)
1.6%
0.9%
0.26
- subacute (>24 hrs – 30d)
2.1%
0.8%
*Protocol definition of stent thrombosis, CEC adjudicated
Dangas et al, SCAI-ACCi2 2008

15. Overall: 30 Day Bleeding Endpoints
300 mg LD
600 mg LD
P-Value
Protocol Major, non CABG
8.7%
5.8%
0.002
Protocol Major, All
11.0%
7.2%
0.0002
Protocol Minor
13.9%
11.2%
0.02
Blood transfusion
3.6%
2.4%
0.057
TIMI Major
4.3%
3.4%
0.19
TIMI Minor
5.6%
2.5%
<0.0001
TIMI Major or Minor
10.0%
6.2%
GUSTO LT* or Severe
0.6%
0.4%
0.33
GUSTO Moderate
4.9%
3.2%
GUSTO LT or Sev or Mod
5.4%
*Life threatening
Dangas et al, SCAI-ACCi2 2008

16. Prediction of 30-day Adverse Outcomes
Multivariate Predictors Using Logistic Regression Model
Hazard Ratio
95% CI p
Death (78 events)
KILLIP class 1
0.3
<0.001
Ccr
0.97
History of PVD
2.01
0.035
Clopidogrel 600mg LD
0.76
0.232
Age -
Death/Reinfarction (127 events)
0.33
Platelet count
1.002
0.029
1.02
1-1.05
0.042
0.7
0.056
Diabetes
History of CHF
US stratification
Dangas et al, SCAI-ACCi2 2008

17. Prediction of 30-day Adverse Outcomes
Multivariate Predictors Using Cox proportional hazards model
Hazard Ratio
95% CI p
MACE (172 events)
KILLIP class 1
0.41
<0.001
Clopidogrel 600mg LD
0.72
0.036
Platelet count
1.002
0.026
Age
1.03
US stratification
1.49
0.019
History of PVD
1.87
0.016
History of CHF -
Major bleeding (226 events)
Bivalirudin
0.57
0.63
0.01
Creatinine clearance
0.99
0.002
Female
1.45
Anemia
1.62
0.008
2.44
IABP
3.53
Closure device
0.80
0.17
0.89
0.39
Dangas et al, SCAI-ACCi2 2008

18. Conclusions In patients with STEMI undergoing primary PCI:
600 mg loading dose of clopidogrel was associated with significantly lower 30- day mortality, reinfarction and stent thrombosis rates compared with 300 mg loading dose.
600 mg loading dose of clopidogrel did not increase the risk of bleeding compared with 300 mg loading dose.
Biv monotherapy significantly reduces major bleeding and NACE, independently of the clopidogrel loading dose.
By multivariate analysis, 600 mg loading dose of clopidogrel was an independent predictor of lower 30-day MACE (compared with 300 mg LD, Odds Ratio=0.72), but was not independently associated with death, reinfarction or major bleeding.
Dangas et al, SCAI-ACCi2 2008

19. Impact Of Diabetes Mellitus On The Safety And Effectiveness Of Bivalirudin In Patients With Acute Myocardial Infarction Undergoing Primary Angioplasty: The HORIZONS AMI Trial
Bernhard Witzenbichler, Giulio Guagliumi, Martin Desaga, Janusz Kochman, Dennis W. Nilsen, Ariel Finkelstein, Morris Mosseri, Helen Parise, Roxana Mehran, Gregg W. Stone

20. Witzenbichler et al ACC 2008
Background
Outcomes in the HORIZONS AMI trial were analyzed according to the presence of medically treated diabetes mellitus (DM) at the time of admission.
This subgroup analysis was pre-specified in the protocol / statistical analysis plan.
Since subgroups are generally underpowered, these analyses will be considered exploratory and hypothesis generating.
Witzenbichler et al ACC 2008

21. Baseline characteristics
593 of study patients (16.5%) in HORIZONS had medically treated diabetes. Baseline characteristics demonstrate that diabetics represent a significantly higher risk group compared to non-diabetics.
Diabetics (N=593; 16.5%)
Non-Diabetics (N=3006; 83.5%)
P value
Age
64.4 [56.0, 71.8]
59.5 [51.8, 69.2]
<0.0001
Male
73.5%
77.2%
0.0504
Weight (kg)
85.0 [75.0, 96.0]
80 [70.0, 90.0]
BMI
28.9 [25.8, 31.9]
26.8 [24.4, 29.7]
Waist circumference (cm)
102.5 [95.0, 112.0]
96.5 [89.0, 105.0]
Hypertension
72.2%
49.8%
Hyperlipidemia
60.0%
39.7%
Current smoker
36.4%
48.0%
Peripheral vasc. Disease
9.1%
3.5%
Renal insufficiency
7.6%
2.0%
Witzenbichler et al ACC 2008

22. Baseline characteristics (ii)
Diabetics (N=593; 16.5%)
Non-Diabetics (N=3006; 83.5%)
P value
Prior MI
16.7%
9.7%
<0.0001
Prior PCI
16.6%
9.6%
Prior CABG
5.4%
2.4%
KILLIP Class 2-4
12.4%
7.7%
0.0002
LVEF<40%
21.4%
13.4%
Symptom onset to hospital arrial, hours
2.3 [1.4, 4.3]
2.1 [1.3, 3.8]
0.0137
Symptom onset to first balloon inflation
4.3 [2.9, 6.4]
3.6 [2.6, 5.5]
Anemia
15.2%
Thrombocytopenia
5.6%
3.9%
0.0629
Witzenbichler et al ACC 2008

23. Endpoints in non-diabetics, by study drug
Non-Diabetics (n=3006)
RR=0.60 [0.61, 0.94]
P=0.006
RR=0.55 [0.41, 0.74]
P=0.001
RR=1.14 [0.83, 1.56]
P= n.s.
*MACE = All cause death, reinfarction, ischemic TVR or stroke
Witzenbichler et al ACC 2008

24. Endpoints in diabetics, by study drug
Diabetics (n=593)
RR=0.60 [0.61, 0.94]
P=0.006
RR=0.55 [0.41, 0.74]
P=0.001
RR=1.14 [0.83, 1.56]
P= n.s.
*MACE = All cause death, reinfarction, ischemic TVR or stroke
Witzenbichler et al ACC 2008

25. 30-day MACE components among diabetics
UFH + GP IIb/IIIa
(N=312)
Bivalirudin
(N=281)
P Value
Death
5.4%
3.6%
0.27
Cardiac
2.1%
0.037
Non cardiac 0%
1.4%
0.0499
Reinfarction
2.9%
0.56
Q-wave
2.2%
0.40%
0.63
Non Q-wave
1.0%
0.4%
Ischemic TVR
2.6%
2.8%
0.83
Ischemic TLR
1.9%
0.46
Ischemic remote TVR
0.6%
1.00
Stroke
0.032
Ischemic
Hemorrhagic
N/A
Witzenbichler et al ACC 2008

26. 30 day bleeding endpoints among diabetics
UFH + GP IIb/IIIa
(N=312)
Bivalirudin
(N=281)
P Value
Protocol Major, non CABG*
9.6%
7.8%
0.44
Protocol Major, ALL
12.2%
11.4%
0.77
Blood transfusion
4.5%
4.3%
0.90
TIMI Major
4.8%
6.4%
0.40
TIMI Minor
5.1%
3.6%
0.35
TIMI Major or Minor
9.9%
10.0%
0.99
GUSTO LT or Severe
1.0%
0.4%
0.63
GUSTO Moderate
5.7%
0.72
GUSTO LT or Sev or Mod
7.1%
6.0%
0.62
Witzenbichler et al ACC 2008

27. Witzenbichler et al ACC 2008
Conclusions
Compared to patients without diabetes mellitus, those with diabetes had greater rates of major bleeding (8.8% vs. 6.2%, P=0.02), MACE (8.1% vs. 5.0%, P=0.002) and NACE (14.2% vs. 10.0%, P=0.003).
Among the diabetic subgroup:
Bivalirudin significantly reduced cardiac death at 30 days (p=0.037).
Total and hemorrhagic stroke rate occurred more often in the UFH + GPI group, whereas non-cardiac death rate was slightly increased in the Bivalirudin group, although based on small patient numbers.
All other 30 day endpoints including stent thrombosis rate were not significantly different among diabetics between the two treatment arms
In patients with AMI undergoing primary PCI, Bivalirudin monotherapy significantly reduces major bleeding and net adverse clinical events, effects which are independent of diabetic status (interaction P value for major bleeding = 0.22, for MACE = 0.10, and NACE = 0.90).
Witzenbichler et al ACC 2008

28. For the HORIZONS AMI Investigators
Impact of Baseline Renal Function on the Safety and Effectiveness of Bivalirudin in Patients with Acute MI Undergoing Primary Angioplasty: The HORIZONS AMI trial
Roxana Mehran, Bernhard Witzenbichler, Giulio Guagliumi, Victor Guetta, Harry Suryapranata, Kurt Huber, Jochen Wöehrle, Chris Metzger, George Dangas, Helen Parise, Gregg W. Stone
For the HORIZONS AMI Investigators

29. Background and Objectives
In HORIZONS, bivalirudin monotherapy compared to heparin + GPI resulted in reduced rates of major bleeding and NACE, with comparable composite MACE in pts undergoing primary PCI.
Whether the beneficial effects of Biv are independent of renal function, an important prognostic determinate after primary PCI, has not been reported.
We evaluated 30-day outcomes overall and by randomized antithrombin treatment according to baseline renal function.
Mehran et al ACC 2008

30. Baseline Characteristics
CrCl ≥60 mL/min
(N=2783)
CrCl <60 mL/min
(N=554)
P-value
Age (years)
57.9 [50.8, 65.5]
75.4 [70.4, 80.3]
<0.0001
Male
81.1%
55.2%
Diabetes
16.0%
19.3%
0.05
Hypertension
49.9%
69.1%
Hyperlipidemia
42.2%
46.2%
0.08
Current smoking
50.4%
24.4%
Prior MI
9.7%
15.3%
Prior PCI
9.8%
13.9%
0.004
Prior CABG
2.3%
5.6%
Mehran et al ACC 2008

31. 30-Day Outcomes by Renal Function
P< for all
*Not related to CABG
**MACE = All cause death, reinfarction, ischemic TVR or stroke
Mehran et al ACC 2008

32. 30-Day Outcomes among Renally Impaired Patients (CrCl <60 mL/min) by Treatment
*Not related to CABG
**MACE = All cause death, reinfarction, ischemic TVR or stroke
Mehran et al ACC 2008

33. 30-Day Outcomes among Pts with Normal Renal Function (CrCl ≥60 mL/min) by Treatment
*Not related to CABG
**MACE = All cause death, reinfarction, ischemic TVR or stroke
Mehran et al ACC 2008

34. Conclusions
Patients with AMI and impaired renal function (CrCl <60 mL/min) undergoing primary PCI have significantly worse 30- day ischemic and bleeding outcomes compared to patients with normal renal function.
There was no significant difference in 30-day outcomes among patients with impaired renal function treated with bivalirudin monotherapy or heparin + GPI in HORIZONS-AMI study.
Among patients with normal renal function, bivalirudin monotherapy significantly reduces major bleeding and net adverse clinical events.
Mehran et al ACC 2008

35. Impact of gender on the safety and effectiveness of bivalirudin in patients with acute myocardial infarction undergoing primary angioplasty L Grinfeld, J Belardi, AJ Lansky, B Witzenbichler, G Guagliumi, K Zmudka, M Moeckel, A Ochala, W Ruzyllo, H Parise, R Mehran, GW Stone

36. Objectives
To evaluate the impact of gender on the safety and effectiveness of bivaliridun monotherapy compared to UFH + the routine use of GP IIb/IIIa inhibitors in patients with AMI undergoing primary angioplasty:
Similar or reduced rates of NACE at 30 days
Similar or reduced rates of major bleeding
Grinfeld et al ACC 2008

37. Demographics Male (N=2760) Female (N=842) p value Age (years)
58.8 [51.4, 67.8]
66.0 [57.1, 75.3]
<
BMI
27.1 [24.7, 30.0]
26.7 [24.0, 30.8]
0.2
Diabetes
15.8%
18.7%
0.05
Hypertension
50.8%
62.3%
<
Hyperlipidemia
42.1%
46.1%
0.04
Current smoking
47.8%
40.8%
0.0004
Prior MI
12.0%
7.4%
0.0002
Prior PCI
11.6%
7.9%
0.002
Prior CABG
3.3%
1.8%
0.03
Grinfeld et al ACC 2008

38. Events by gender Male (N=2760) Female (N=842) p value
1° Endpoint (MACE or major bleeding)
9.2%
15.6%
<
MACE (death, MI, ischemic TVR or stroke)
4.9%
7.4%
0.006
Death
2.2%
3.8%
0.01
Reinfarction
1.8%
2.1%
0.6
Stroke
0.6%
0.8%
0.5
Ischemic TVR
2.0%
3.4%
0.02
Major bleeding (Non-CABG related)
5.7%
10.1%
< 0.001
Minor bleeding
7.8%
14.3%
Grinfeld et al ACC 2008

39. Events by gender (male)
RR=0.77 [0.59, 0.97]
P=0.03
RR=0.59 [0.43, 0.82]
P=0.001
P= ns
Grinfeld et al ACC 2008

40. Events by gender (female)
RR=0.76 [0.54, 1.08]
P=0.01
RR=0.59 [0.38, 0.92]
P=0.02
P= ns
Grinfeld et al ACC 2008

41. Conclusions
Women and men with AMI undergoing PCI have different risk profiles.
Women have a higher incidence of death, ischemic TVR, major and minor bleeding.
Despite these differences, bivalirudin monotherapy significantly reduces major bleeding and net adverse clinical events compared to UFH plus the routine use of GP IIb/IIIa inhibitors both in women and men.
Grinfeld et al ACC 2008

42. Impact of advanced age on the safety and effectiveness of bivalirudin in patients with acute myocardial infarction undergoing primary angioplasty: The HORIZONS AMI trial Dariusz Dudek, Krzyszto Zmudka, Bernhard Witzenbichler, Giulio Guagliumi, Jan Z. Peruga, Bruce R. Brodie, Ran Kornowski, Franz Hartmann, Martin Mockel, Andrzej Ochala, Helen Parise, Roxana Mehran, Gregg W. Stone

43. Methods
A total of 3602 patients at 123 centers in 11 countries with AMI undergoing primary PCI were randomized to bivalirudin monotherapy or unfractionated heparin plus glycoprotein IIb/IIIa inhibitors.
Outcomes were analyzed according to age above or below the median of 60.2 years:
Bivalirudin (n=1800)
age ≤60.2 years (n=923)
age >60.2 years (n=877)
UFH+GPI (n=1802)
age ≤60.2 years (n=885)
age >60.2 years (n=917)
Dudek et al ACC 2008

44. Outcomes, Age ≤ 60.2 years *P<0.05 P=0.168 P=0.0012* P=0.354
Dudek et al ACC 2008

45. Outcomes, Age > 60.2 years
P=0.156
P=0.013*
P=0.512
P=0.033*
*P<0.05
Dudek et al ACC 2008

46. Conclusions
In patients with AMI undergoing primary PCI, bivalirudin monotherapy significantly reduces major bleeding and net adverse clinical events, effects which are independent of age.
Dudek et al ACC 2008

47. Safety and effectiveness of bivalirudin compared to either abciximab or eptifibatide in patients with acute myocardial infarction undergoing primary angioplasty: The HORIZONS AMI trial Giulio Guagliumi, Bernhard Witzenbichler, Jan Z. Peruga, Bruce R. Brodie, Dariusz Dudek, Ran Kornowski, Janusz Kochman, Yaron Almagor, Dennis Nilsen, Ajay Kirtane, Helen Parise, Roxana Mehran, Gregg W. Stone

48. Methods
A total of 1,915 pts (53%) were randomized in the abciximab strata, and 1,687 pts (47%) were randomized in the eptifibatide strata. Subgroup analyses pre-specified in the protocol.
Gualiumi et al ACC 2008

49. Outcomes, abciximab strata (n=1915)
RR=0.57 [0.39, 0.85]
RR=0.91 [0.61, 1.36]
RR=0.73 [0.55, 0.97]
*MACE = death, reinfarction, ischemic TVR or stroke
**NACE = (Net Adverse Clinical Events) = MACE or major bleeding
Gualiumi et al ACC 2008

50. Outcomes, eptifibatide strata (n=1687)
RR=0.57 [0.39, 0.85]
RR=0.91 [0.61, 1.36]
RR=0.73 [0.55, 0.97]
*MACE = death, reinfarction, ischemic TVR or stroke
**NACE = (Net Adverse Clinical Events) = MACE or major bleeding
Gualiumi et al ACC 2008

51. Conclusions
In patients with AMI undergoing primary PCI, bivalirudin monotherapy significantly reduces major bleeding and net adverse clinical events compared to UFH with either abciximab or double-bolus eptifibatide.
Gualiumi et al ACC 2008

52. Major Adverse Events in STEMI Patients Treated with Primary Angioplasty Occur More Frequently at U.S. Compared with Non U.S. Sites: Analysis from the HORIZONS AMI Trial Bruce R. Brodie, Thomas Stuckey, Bernhard Witzenbichler, Giulio Guagliumi, Jan Z. Peruga, Dariusz Dudek, Ran Kornowski, Franz Hartmann, George Dangas, S.Chiu Wong, Helen Parise, Roxana Mehran, Gregg W. Stone

53. Background
The HORIZONS trial trial provided an opportunity to compare outcomes with primary PCI for STEMI at sites in the United States versus at sites outside the United States. This has not been previously evaluated.
Patients enrolled outside of the United States in Europe, Israel and Argentina (OUS) (n = 2,788) were compared with patients enrolled in the United States (US) (n = 814).
Brodie et al ACC 2008

54. Baseline DemographicsUS
(N=814)
OUS
(N=2788) p value
Age (years)
59.8 NS
Gender (Male)
74.8%
77.2% NS
Race
White
84.4%
96.5% <0.0001
Black
8.1%
0.2% <0.0001
Hispanic
6.2%
2.4% <0.0001
Asian
0.5%
0.7% NS
Brodie et al ACC 2008

55. Baseline Clinical VariablesUS
(N=814)
OUS
(N=2788) p value
Diabetes
20.8%
15.2%
Hypertension
59.1%
51.8%
Hyperlipidemia
46.8%
42.0%
Current Smoker
43.0%
47.1%
Prior MI
13.8%
10.1%
Prior CABG
5.5%
2.2% <0.0001
Killip Class 3-4
2.1%
1.5% NS
BMI
28.0
<0.0001
Renal Insufficiency
4.7%
2.4%
Brodie et al ACC 2008

56. Angiographic VariablesUS
(N=814)
OUS
(N=2788) p value
Infarct Artery
LAD
35.3%
42.1%
CFX
15.1%
16.0% NS
RCA
47.1%
40.6%
SVG
2.1%
0.6%
LVEF < 40%
20.8%
12.7% <0.0001
TIMI 2-3 Flow Initial
31.1%
35.6%
Symtom –Door (hrs)
1.8
<0.0001
Door-Angio (min) 67
Brodie et al ACC 2008

57. Primary Management StrategyUS
OUS
Primary PCI
Deferred PCI
CABG
Medical Rx
89.6%
93.7%
Brodie et al ACC 2008

58. Adjunctive PharmacologyUS
(N=814)
OUS
(N=2788) p value
Pre-rand Heparin
70.8%
64.0%
Clopidogrel Load
300 mg
49.6%
30.8% <0.0001
600 mg
49.7%
67.7% <0.0001
Any IIb/IIIa Inhibitor
55.7%
54.0% NS
Abciximab
43.4%
55.4%
Eptifibatide
56.6%
43.9% <0.0001
Tirofiban 0%
0.9%
Bail-out IIb/IIIa Inhib
10.1%
6.8%
Brodie et al ACC 2008

59. 30 Day Outcomes: US vs OUS Adjusted Hazard Ratios (95% CI) US Better
DEATH
DEATH/MI
MACE
MAJOR BLEEDING
NACE
US Better
OUS Better
Brodie et al ACC 2008

60. Conclusions
STEMI patients enrolled in the HORIZONS-AMI Trial in the US had a much higher risk profile than patients enrolled outside the US.
HORIZONS patients treated with primary PCI in the US had higher rates of death, death/MI, MACE, major bleeding and NACE compared with OUS patients.
After adjusting for differences in baseline variables, US patients had significantly higher rates of MACE, Major Bleeding and NACE compared with OUS patients.
Both US and OUS patients had lower event rates with bivalirudin compared with IIb/IIIa platelet inhibitors. There were no significant interactions between US vs OUS sites and randomization treatment.
Brodie et al ACC 2008