1. Results of the EUROMAX trial
Philippe Gabriel Steg*, Arnoud van ‘t Hof, Christian W. Hamm, Peter Clemmensen, Frédéric Lapostolle, Pierre Coste, Jurrien Ten Berg, Pierre Van Grunsven, Gerrit Jan Eggink, Lutz Nibbe, Uwe Zeymer, Marco Campo dell' Orto, Holger Nef, Jacob Steinmetz, Louis Soulat, Kurt Huber, Efthymios N. Deliargyris, Debra Bernstein, Diana Schuette, Jayne Prats, Tim Clayton, Stuart Pocock, Martial Hamon, Patrick Goldstein, for the EUROMAX Investigators**
*Hôpital Bichat, Assistance Publique – Hôpitaux de Paris, Université Paris – Diderot, INSERM U-698, Paris, France, and NHLI Imperial College, ICMS, Royal Brompton Hospital, London, UK
**A complete list is available in Steg PG et al. Design and methods of the EUROMAX trial. Am Heart J 2013

2. Ph. Gabriel Steg – Disclosures
Research grant (to INSERM U698): NYU school of Medicine, Sanofi, Servier
Speaking or consulting: Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Glaxo-SmithKline, Iroko Cardio, Lilly, Medtronic, Novartis, Otsuka, Pfizer, Sanofi, Servier, The Medicines Company, Vivus
Stockholding: Aterovax
The EUROMAX trial was funded by The Medicines Company

3. Bivalirudin for PPCI in STEMI
The HORIZONS AMI trial established the role of bivalirudin in PPCI, with a reduction in mortality and in bleeding sustained up to 3 years compared to UFH + GPI
However, there are new questions:
What is the role of bivalirudin in the ambulance for patients triaged to primary PCI (from the pre-hospital setting or from non–PCI-capable hospitals) ?
Is it possible to reduce the risk of acute stent thrombosis by using a prolonged infusion of bivalirudin at the end of PCI ?
What is the impact of contemporary practice (e.g. novel P2Y12 inhibitors, increased use of radial arterial access, no systematic use of GPIs) on efficacy and safety of bivalirudin ?

4. EUROMAX Trial Design Bivalirudin UFH/LMWH ± GPI Per standard practice
2218 patients with STEMI with symptom onset >20 min and ≤12h Randomized in ambulance or non-PCI hospital
Intent for primary PCI
Aspirin + P2Y12 inhibitor (any) as soon as possible R
1:1
UFH/LMWH ± GPI
Per standard practice
Bivalirudin
(0.75 mg/kg bolus, 1.75 mg/kg/h infusion)
+ prolonged optional infusion
(PCI dose or 0.25 mg/kg/h)
(provisional GPI only)
Primary endpoint: 30-day death or non-CABG related major bleeding
Key Secondary endpoint: Death, Re-infarction or non-CABG major bleeding at 30 days
Clinical FU at 30 days and 1 year
clinicaltrials.gov NCT

5. EUROMAX - A European Trial
France – 795
Netherlands – 768
Germany – 279
Denmark – 150
Slovenia
Czech Rep.
Poland
Italy
Austria
206

6. Baseline Characteristics
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Age — median (IQR), yr
61 (52, 71)
62 (52, 72)
Age >65 yr — no. (%)
394 (36.2)
434 (39.1)
Female sex — no. (%)
275 (25.3)
248 (22.4)
Diabetes — no. (%)
127 (11.7)
169 (15.3)*
Hypertension — no. (%)
459 (42.2)
504 (45.5)
Hyperlipidemia‡ — no. (%)
398 (36.6)
417 (37.6)
Current smoker — no. (%)
453 (41.6)
472 (42.6)
Prior myocardial infarction — no. (%)
80 (7.4)
113 (10.2)*
Prior PCI — no. (%)
97 (8.9)
108 (9.7)
Prior CABG — no. (%)
18 (1.7)
29 (2.6)
Killip class II, III, or IV — no. (%)
77 (7.7)
69 (6.9)
Anemia — no. (%)
129 (13.1)
148 (15.0)
Creatinine clearance — no. (%)
≤60 mL/min
147 (14.7)
165 (16.5)
>60 mL/min
854 (85.3)
833 (83.5)
* P < 0.05 between groups

7. Procedures, Medications
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Randomized in ambulance no. (%)
1030 (94.6)
1045 (94.2)
Randomized in non–PCI-capable hospital— no. (%)
59 (5.4)
64 (5.8)
Aspirin use — no. (%)
1088 (100)
1107 (99.8)
P2Y12 inhibitor loading dose — no. (%)
Yes
1048/1066 (98.3)
1058/1083 (97.7)
Clopidogrel
524/1048 (50.0)
545/1058 (51.5)
Ticlopidine
0 (0.0)
2 (0.2)
Prasugrel
323/1048 (30.8)
306/1058 (28.9)
Ticagrelor
201/1048 (19.2)
205/1058 (19.4)
P2Y12 loading before angiography — no. (%)
913/1011 (90.3)
923/1010 (91.4)
Maintenance dose - yes
957/1065 (89.9) 
969/1082 (89.6)
377/957 (39.4)
407/969 (42.0)
2/957 (0.2)
5/969 (0.5)
321/957 (33.5)
298/969 (30.8)
257/957 (26.9)
259/969 (26.7)

8. Procedures, Medications, con’t
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Initial anticoagulation — no. (%)
Bivalirudin
1074 (98.6)
29 (2.6)
Unfractionated heparin
24 (2.2)
997 (89.9)
Enoxaparin
94 (8.5)
Time from initiating anticoagulation to angiography — median (IQR), min
50.0 (37−67)
50.0 (37−65)
Glycoprotein IIb/IIIa inhibitor use — no. (%)
125/1088 (11.5)
766/1109 (69.1)*
Routine
42/1088 (3.9)‡
649/1109 (58.5)*
Bailout§
83/1046 (7.9)
117/460 (25.4)*
Femoral access — no. (%)
558/1069 (52.2)
582/1084 (53.7)
Radial access — no. (%)
510/1069 (47.7)
502/1084 (46.3)
* P < 0.05 between groups
‡ Deviations from the protocol
§ Data given for those eligible for bailout (i.e. who did not receive routine GPI).

9. Procedural Characteristics
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Single vessel disease — no. (%)
591/1069 (55.3)
556/1083 (51.3)
Infarct artery treated with primary PCI — no. (%)
Left main coronary artery
 6/943 (0.6)
 13/946 (1.4)
Left anterior descending artery
425/943 (45.1)
423/946 (44.7)
Left circumflex coronary artery
115/943 (12.2)
132/946 (14.0)
Right coronary artery
417/943 (44.2)
412/946 (43.6)
Bypass graft (venous or arterial)
4/943 (0.4)
10/946 (1.1)
Balloon angioplasty only — no. (%)
48/943 (5.1)
42/946 (4.4)
Stents implanted — no. (%)
868/943 (92.0)
865/946 (91.4)
Drug-eluting stent
538/943 (57.1)
529/946 (55.9)
Thrombectomy — no. (%)
304/943 (32.2)
298/946 (31.5)
Pre-PCI TIMI flow — no. (%)
0/1
593/931 (63.7)
563/932 (60.4) 2
143/931(15.4)
158/932 (17.0) 3
195/931 (20.9)
211/932 (22.6)
Post-PCI TIMI flow — no. (%)
18/930 (1.9)
16/932 (1.7)
29/930 (3.1)
31/932 (3.3)
883/930 (94.9)
885/932 (95.0)
CABG during hospitalization
21/1089 (1.9)
29/1109 (2.6)

10. Medications at Discharge (ITT)
Variable — no. (%)
Bivalirudin
(N=1089)
Heparins + optional GPI
(N=1109)
ACE inhibitor or ARB
718 (65.9)
709 (63.9)
Aspirin
1000 (91.8)
1012 (91.3)
Beta-blocker
944 (86.7)
957 (86.3)
P2Y12 inhibitor
938 (86.1)
941 (84.9)
Statin
968 (88.9)
997 (89.9)

11. Primary Endpoint: Death or Major Bleed, 30 day
Bivalirudin
Heparins with optional GPI
8.4%
Event Rate
5.1%
Log-rank p = 0.002
Days from Randomization Date
Patients at risk:
Bivalirudin
1089
1038
1024
1020
1007
988
791
Heparins with optional GPI
1109
1003
998
984
958
765

12. Principal Secondary Endpoint: Death/Reinfarction/Major Bleed, 30 day
Bivalirudin
Heparins with optional GPI
9.1%
6.7%
Event Rate
Days from Randomization Date
Patients at risk:
Bivalirudin
1089
1027
1010
1005
990
971
779
Heparins with optional GPI
1109
1020
996
975
949
760

13. Cardiac and Non-Cardiac Death, 30-day
Bivalirudin
Heparins with optional GPI
Log-rank p = 0.46
3.0%
Cardiac
2.4%
Event Rate
Log-rank p = 0.10
Non-cardiac
0.5%
0.1%
Days from Randomization Date
Patients at risk:
Bivalirudin
1089
1057
1048
1044
1039
1036
1034
Heparins with optional GPI
1109
1062
1061
1056
1050
1043
1037

14. Non–CABG-related major bleed, 30 day
Bivalirudin
Heparins with optional GPI
6.1%
Event Rate
Log-rank p < 0.001
2.7%
Days from Randomization Date
Patients at risk:
Bivalirudin
1089
1040
1025
1022
1010
991
794
Heparins with optional GPI
1109
1030
1009
1005
990
964
773

15. NACE: Death, Reinfarction, IDR, Stroke, Major Bleed, 30 day
Bivalirudin
Heparins with optional GPI
10.7%
7.9%
Event Rate
Log-rank p = 0.024
Days from Randomization Date
Patients at risk:
Bivalirudin
1089
1018
998
992
977
959
769
Heparins with optional GPI
1109
1012
983
976
960
934
746

16. Clinical Outcomes, 30 days
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Relative risk
[95% CI]
P Value
Death or major bleeding (non-CABG) (primary outcome)
55 (5.1)
94 (8.5)
0.60 (0.43–0.82)
0.001
Death, reinfarction, or major bleeding (non-CABG)
(key secondary outcome)
72 (6.6)
102 (9.2)
0.72 (0.54–0.96)
0.02
Death
32 (2.9)
34 (3.1)
0.96 (0.60–1.54)
0.86
Cardiac causes
27 (2.5)
33 (3.0)
0.83 (0.50–1.38)
0.48
Noncardiac causes
5 (0.5)
1 (0.1)
5.09 (0.60–43.51)
0.12
Major bleeding (non-CABG)
28 (2.6)
67 (6.0)
0.43 (0.28–0.66)
<0.001
Major adverse cardiovascular events*
65 (6.0)
61 (5.5)
1.09 (0.77–1.52)
0.64
Net adverse clinical events *
85 (7.8)
118 (10.6)
0.73 (0.56–0.96)
*Patients may have experienced more than one event.
MACE denotes death, reinfarction, ischemia-driven revascularization or stroke;
NACE denotes (death, reinfarction, ischemia-driven revascularization, stroke, or non–CABG major bleeding)

17. Heparins with optional GPI (N=1109)
Bleeding rates, 30 days
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Relative risk
[95% CI]
P Value
Major bleeding (non-CABG)
28 (2.6)
67 (6.0)
0.43 (0.28–0.66)
<0.001
Major or minor bleeding (non-CABG)
85 (7.8)
149 (13.4)
0.58 (0.45–0.75)
TIMI major bleeding (non-CABG)
14 (1.3)
23 (2.1)
0.62 (0.32–1.20)
0.15
TIMI major/minor bleeding (non-CABG)
146 (13.2)
0.59 (0.46–0.76)
GUSTO severe/life-threatening bleeding (non-CABG)
6 (0.6)
10 (0.9)
0.61 (0.22–1.68)
0.33
GUSTO severe/life-threatening or moderate bleeding (non-CABG)
26 (2.3)
0.55 (0.29–1.04)
0.06
GUSTO any bleeding (non-CABG)
148 (13.3)
Blood transfusion
43 (3.9)
0.54 (0.33–0.90)
0.02
Patients may have experienced more than one event.

18. Heparins with optional GPI (N=1109)
Outcomes, 30 days, con’t
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Relative risk
[95% CI]
P Value
Reinfarction
19 (1.7)
10 (0.9)
1.93 (0.90–4.14)
0.08
Q-wave
3 (0.3)
2 (0.2)
1.53 (0.26–9.12)
0.68
Non-Q-wave
16 (1.5)
8 (0.7)
2.04 (0.88–4.74)
0.09
Stent thrombosis (ARC definition)
17 (1.6)
6 (0.5)
2.89 (1.14–7.29)
0.02
Definite
Probable
0 (0) –
n/a
Acute (≤24 hours)
12 (1.1)
6.11 (1.37–27.24)
0.007
Subacute (>24 hours to 30 days)
5 (0.5)
4 (0.4)
1.27 (0.34–4.73)
0.75
Ischemia-driven revascularization
24 (2.2)
17 (1.5)
1.44 (0.78–2.66)
0.25
Reinfarction, ischemia-driven revascularization or stent thrombosis
29 (2.7)
21 (1.9)
1.41 (0.81–2.45)
0.23
Any stroke
6 (0.6)
11 (1.0)
0.56 (0.21–1.50)
0.24
Ischemic
9 (0.8)
0.68 (0.24–1.9)
0.46
Hemorrhagic
Not applicable
0.50
Acquired thrombocytopenia
7 (0.7)
14 (1.4)
0.50 (0.20–1.24)
0.13
n/a: not applicable.

19. Subgroup Analysis: Death/Major Bleed at 30 Days (ITT)
Bivalirudin (N=1089) n/N (%)
Heparins with optional GPI (N=1109) n/N (%)
Relative Risk (95% CI)
Interaction
P-value
ALL
55/1089 (5.1)
94/1109 (8.5)
0.60 [0.43, 0.82)
Age
>65 years
39/394 (9.9)
61/434 (14.1)
0.70 [0.48, 1.03]
0.31
≤65 years
16/695 (2.3)
33/675 (4.9)
0.47 [0.26, 0.85]
Sex
Male
32/814 (3.9)
64/861 (7.4)
0.53 [0.35, 0.80]
0.47
Female
23/275 (8.4)
30/248 (12.1)
0.69 [0.41, 1.16]
Diabetes
Yes
12/127 (9.4)
18/169 (10.7)
0.89 [0.44, 1.77]
0.26 No
40/946 (4.2)
71/926 (7.7)
0.55 [0.38, 0.80]
Arterial access site
Radial
20/510 (3.9)
33/502 (6.6)
0.60 [0.35, 1.03]
0.97
Femoral
31/558 (5.6)
53/582 (9.1)
0.61 [0.40, 0.94]
Vessels with stenosis >50%
1 vessel with stenosis >50%
19/591 (3.2)
33/556 (5.9)
0.54 [0.31, 0.94]
0.66
≥2 vessels with stenosis >50%
28/407 (6.9)
49/462 (10.6)
0.65 [0.42, 1.01]
Stent type
At least one drug-eluting stent
22/538 (4.1)
39/529 (7.4)
0.55 [0.33, 0.92]
0.84
All bare metal stents
16/330 (4.8)
27/336 (8.0)
0.60 [0.33, 1.10]
0.1
1.0
10.0
Bivalirudin better
Heparins with optional GPI better

20. Subgroup Analysis: Death/Major Bleed at 30 Days (ITT)
Bivalirudin (N=1089) n/N (%)
Heparins with optional GPI (N=1109) n/N (%)
Relative Risk (95% CI)
Interaction
P-value
Killip class 1
32/919 (3.5)
59/931 (6.3)
0.55 [0.36, 0.84]
0.58
2-4
14/ 77 (18.2)
24/ 69 (34.8)
0.52 [0.29, 0.93]
P2Y12 inhibitor loading dose
Clopidogrel
25/524 (4.8)
38/545 (7.0)
0.68 [0.42, 1.12]
0.82
Prasugrel
16/323 (5.0)
22/306 (7.2)
0.69 [0.37, 1.29]
Ticagrelor
11/201 (5.5)
21/205 (10.2)
0.53 [0.26, 1.08]
P2Y12 inhibitor maintenance dose
19/377 (5.0)
28/407 (6.9)
0.73 [0.42, 1.29]
0.24
16/321 (5.0)
19/298 (6.4)
0.78 [0.41, 1.49]
7/257 (2.7)
21/259 (8.1)
0.34 [0.15, 0.78]
Time on drug to angiography
<50 min
23/514 (4.5)
42/495 (8.5)
0.53 [0.32, 0.86]
0.48
≥50 min
27/549 (4.9)
42/576 (7.3)
0.67 [0.42, 1.08]
Baseline creatinine clearance
≤60
21/147 (14.3)
30/165 (18.2)
0.79 [0.47, 1.31]
0.44
>60
28/854 (3.3)
48/833 (5.8)
0.57 [0.36, 0.90]
Target Vessel
Left anterior descending (LAD)
30/425 (7.1)
42/423 (9.9)
0.71 [0.45, 1.11]
0.30
No LAD
25/664 (3.8)
52/686 (7.6)
0.50 [0.31, 0.79]
0.1
1.0
10.0
Bivalirudin better
Heparins with optional GPI better

21. Subgroup Analysis: Death/Reinfarction/Major Bleed at 30 Days (ITT)
Bivalirudin (N=1089) n/N (%)
Heparins with optional GPI (N=1109) n/N (%)
Relative Risk (95% CI)
Interaction
P-value
ALL
72/0189 (6.6)
102/1109 (9.2)
0.72 [ ]
Age
>65 years
45/394 (11.4)
65/434 (15.0)
0.76 [0.53, 1.09]
0.88
≤65 years
27/695 (3.9)
37/675 (5.5)
0.71 [0.44, 1.15]
Sex
Male
43/814 (5.3)
71/861 (8.2)
0.64 [0.44, 0.92]
0.40
Female
29/275 (10.5)
31/248 (12.5)
0.84 [0.52, 1.36]
Diabetes
Yes
14/127 (11.0)
20/169 (11.8)
0.93 [0.49, 1.77]
0.43 No
54/946 (5.7)
77/926 (8.3)
0.69 [0.49, 0.96]
Arterial access site
Radial
26/510 (5.1)
35/502 (7.0)
0.73 [0.45, 1.20]
0.99
Femoral
42/558 (7.5)
59/582 (10.1)
0.74 [0.51, 1.08]
Vessels with stenosis >50%
1 vessel with stenosis >50%
25/591 (4.2)
35/556 (6.3)
0.67 [0.41, 1.11]
0.61
≥2 vessels with stenosis >50%
39/407 (9.6)
55/462 (11.9)
0.80 [0.55, 1.19]
Stent type
At least one drug-eluting stent
29/538 (5.4)
44/529 (8.3)
0.65 [0.41, 1.02]
0.46
All bare metal stents
24/330 (7.3)
29/336 (8.6)
0.84 [0.50, 1.42]
Killip class 1
47/919 (5.1)
67/931 (7.2)
0.71 [0.50, 1.02]
0.24
2-4
14/77 (18.2)
24/69 (34.8)
0.52 [0.29, 0.93]
P2Y12 inhibitor loading dose
Clopidogrel
32/524 (6.1)
45/545 (8.3)
0.74 [0.48, 1.15]
0.80
Prasugrel
21/323 (6.5)
22/306 (7.2)
0.90 [0.51, 1.61]
Ticagrelor
15/201 (7.5)
22/205 (10.7)
0.70 [0.37, 1.30]
P2Y12 inhibitor maintenance dose
24/377 (6.4)
32/407 (7.9)
0.81 [0.49, 1.35]
0.22
22/321 (6.9)
20/298 (6.7)
1.02 [0.57, 1.83]
11/257 (4.3)
24/259 (9.3)
0.46 [0.23, 0.92]
Time on drug to angiography
<50 min
34/514 (6.6)
45/495 (9.1)
0.73 [0.47, 1.12]
0.96
≥50 min
33/549 (6.0)
47/576 (8.2)
0.74 [0.48, 1.13]
Baseline creatinine clearance
≤60
22/147 (15.0)
31/165 (18.8)
0.80 [0.48, 1.31]
0.98
>60
44/854 (5.2)
55/833 (6.6)
0.78 [0.53, 1.15]
Target Vessel
Left anterior descending (LAD)
36/425 (8.5)
46/423 (10.9)
0.78 [0.51, 1.18]
No LAD
36/664 (5.4)
56/686 (8.2)
0.66 [0.44, 1.00]
Bivalirudin better
Heparins with optional GPI better

22. Subgroup Analysis: Major Bleed at 30 Days (ITT)
Bivalirudin (N=1089) n/N (%)
Heparins with optional GPI (N=1109) n/N (%)
Relative Risk (95% CI)
Interaction
P-value
ALL
28 /1089 (2.6)
67 /1109 (6.0)
0.43 [0.28, 0.66]
Age
>65 years
19/394 (4.8)
39/434 (9.0)
0.54 [0.32, 0.91]
0.28
≤65 years
9/695 (1.3)
28/675 (4.1)
0.31 [0.15, 0.66]
Sex
Male
15/814 (1.8)
43/861 (5.0)
0.37 [0.21, 0.66]
0.58
Female
13/275 (4.7)
24/248 (9.7)
0.49 [0.25, 0.94]
Diabetes
Yes
5/127 (3.9)
9/169 (5.3)
0.74 [0.25, 2.15]
0.25 No
22/946 (2.3)
58/926 (6.3)
0.37 [0.23, 0.60]
Arterial access site
Radial
14/510 (2.7)
25/502 (5.0)
0.55 [0.29, 1.05]
0.35
Femoral
14/558 (2.5)
40/582 (6.9)
0.37 [0.20, 0.66]
Vessels with stenosis >50%
1 vessel with stenosis >50%
12/591 (2.0)
27/556 (4.9)
0.42 [0.21, 0.82]
0.72
≥2 vessels with stenosis >50%
15/407 (3.7)
34/462 (7.4)
0.50 [0.28, 0.91]
Stent type
At least one drug-eluting stent
15/538 (2.8)
31/529 (5.9)
0.48 [0.26, 0.87]
0.59
All bare metal stents
7/330 (2.1)
20/336 (6.0)
0.36 [0.15, 0.83]
Killip class 1
17/919 (1.8)
49/931 (5.3)
0.35 [0.20, 0.61]
0.27
2-4
9/77 (11.7)
12/69 (17.4)
0.67 [0.30, 1.50]
P2Y12 inhibitor loading dose
Clopidogrel
12/524 (2.3)
24/545 (4.4)
0.52 [0.26, 1.03]
0.41
Prasugrel
12/323 (3.7)
19/306 (6.2)
0.60 [0.30, 1.21]
Ticagrelor
4/201 (2.0)
16/205 (7.8)
0.25 [0.09, 0.75]
P2Y12 inhibitor maintenance dose
9/377 (2.4)
21/407 (5.2)
0.46 [0.21, 1.00]
0.16
14/321 (4.4)
17/298 (5.7)
0.76 [0.38, 1.52]
4/257 (1.6)
18/259 (6.9)
0.22 [0.08, 0.65]
Time on drug to angiography
<50 min
13/514 (2.5)
29/495 (5.9)
0.43 [0.23, 0.82]
0.93
≥50 min
15/549 (2.7)
35/576 (6.1)
0.45 [0.25, 0.81]
Baseline creatinine clearance
≤60
8/147 (5.4)
21/165 (12.7)
0.43 [0.20, 0.94]
0.96
>60
18/854 (2.1)
42/833 (5.0)
0.42 [0.24, 0.72]
Target Vessel
Left anterior descending (LAD)
19/425 (4.5)
30/423 (7.1)
0.63 [0.36, 1.10]
0.05
No LAD
9/664 (1.4)
37/686 (5.4)
0.25 [0.12, 0.52]
Bivalirudin better
Heparins with optional GPI better

23. Limitations of the study
The study was open-label, for logistical reasons.
In order to reduce sample size, the primary endpoint was changed (while still entirely blinded to results) from an original composite of death/reinfarction/major bleeding to death/major bleeding, retaining the original composite as key secondary endpoint.
The trial was not powered to examine 30-day mortality.
Although the trial allowed use of UFH or enoxaparin in the control arm, too few patients received the latter to reliably test the consistency of the benefit of bivalirudin across heparins.

24. Conclusions
Prehospital initiation of bivalirudin, as compared with heparin with optional use of glycoprotein IIb/IIIa inhibitors, reduced the primary composite and the key secondary outcomes in patients with STEMI who were being transported for primary PCI.
These benefits, which were consistent across subgroups, stemmed from substantial reductions in major bleeding.
However, the risk of acute stent thrombosis was higher in the bivalirudin group.
These results were achieved on a background of contemporary care, with a high rate of radial access, use of novel P2Y12 inhibitors, and optional GPI use in the control arm.
They inform pre-hospital management of STEMI and support a role for bivalirudin in this setting.

25. Study Committees Executive Committee
Ph.G. Steg (Chair), J. Adgey, P. Clemmensen, P. Goldstein, M. Hamon, A. van ‘t Hof, L. Nibbe, U. Zeymer
International Steering Committee
C.W. Hamm (Chair); J. Hill, Tom Quinn (UK); P. Clemmensen, J. Steinmetz (Denmark); P. Coste, F. Lapostolle (France); C. Cavallini, G. Gordini; F.W.A. Verheugt, J. ten Berg (Netherlands); U. Zeymer, L. Nibbe (Germany); M. Hirschl, K. Huber (Austria); A. Cequier (Spain); D. Dudek (Poland); P. Widimský (Czech Republic); V. Kanic (Slovenia)
Data Monitoring Committee
N. Danchin (Chair), I. Ford, A. Maggioni, R. Mehran, G. Montalescot
Independent statistician (interim analysis)
C.R. Mehta
Independent statistical group
T.C. Clayton, S.J. Pocock
Clinical Events Committee
K. Thygesen, J. Peder Bagger

26. Steg PG, van’t Hof A, Hamm CW et al. N Engl J Med 2013
For full details (including the protocol, statistical analysis plan and supplementary data appendix),
go to
Steg PG, van’t Hof A, Hamm CW et al. N Engl J Med 2013

27. Backup slides

28. Patient Disposition
2218 Patients with presumed STEMI and symptom onset ≤12 hours underwent randomization
1102 assigned to bivalirudin after initial consent*
1089/1102 (98.8%) provided written final informed consent
1116 assigned to standard of care after initial consent*
1109/1116 (99.4%) provided written final informed consent
1069/1089 (98.2%) underwent emergent angiography
Principal management strategy:
949/1069 (88.8%) Primary PCI
17/1069 (1.6%) CABG
103/1069 (9.6%) Medical Management
1084/1109 (97.7%) underwent emergent angiography
Principal management strategy:
947/1084 (87.4%) Primary PCI
25/1084 (2.3%) CABG
112/1084 (10.3%) Medical Management
8 withdrew consent
7 were lost to follow-up
8 withdrew consent
15 were lost to follow-up
1074/1089 (98.6%) completed 30 days in the study
1086/1109 (97.9%) completed 30 days in the study
1089 were included in the intention-to-treat analysis
1109 were included in the intention-to-treat analysis

29. Components of Major Bleeding Up to 30 Days, ITT
Bivalirudin (N=1089)
Heparins with optional GPI (N=1109)
Relative risk
[95% CI]
P Value
Intracranial
0/1089 (0.0)
2/1109 (0.2)
N/A
0.50
Retroperitoneal
2/1089 (0.2)
0/1109 (0.0)
0.25
Intraocular
Cardiac tamponade
1/1089 (0.1)
1/1109 (0.1)
1.02 [0.06, 16.26]
1.00
Access site hemorrhage requiring intervention
3/1089 (0.3)
12/1109 (1.1)
0.25 [0.07, 0.90]
0.02
Clinically overt bleed
4/1109 (0.4)
0.51 [0.09, 2.77]
0.69
Drop in hemoglobin or hematocrit
12/1089 (1.1)
34/1109 (3.1)
0.36 [0.19, 0.69]
0.001
Reoperation for bleeding
0.12
Blood transfusion
8/1089 (0.7)
24/1109 (2.2)
0.34 [0.15, 0.75]
0.005
Hemodynamic compromise
0.51 [0.05, 5.61]
* Patients may have experienced more than one event.
CI denotes confidence interval, GPI glycoprotein inhibitor, and NA not applicable.

30. Main Inclusion and Exclusion Criteria
Patients presenting ≤12 h of symptom onset with a presumed diagnosis of STEMI
either ST-segment elevation ≥1 mm in 2 contiguous ECG leads, or
presumed new LBBB or ST-segment depression ≥1 mm in at least 2 leads in V1–V3 with a positive terminal T wave
Scheduled for angiography with anticipated primary PCI <2 h after first medical contact
Excluded:
treatment with any injectable anticoagulant immediately before randomization
previous oral anticoagulation
recent surgery
bleeding history