AIDA STEMI TRIAL

1. Journal Club
Dr Awadhesh Kumar Sharma

3. Intracoronary Compared with Intravenous
Bolus Abciximab Application
During Primary
Percutaneous Coronary Intervention
Cardiac Magnetic Resonance Substudy of the
AIDA STEMI trial
Holger Thiele, MD; Jochen Wöhrle, MD
Henning Suenkel, BSc; Josephine Meissner, MD; Sebastian Kerber, MD;
Bernward Lauer, MD; Matthias Pauschinger, MD; Ralf Birkemeyer, MD; Christoph Axthelm, MD;
Rainer Zimmermann, MD; Petra Neuhaus, PhD; Oana Brosteanu, PhD; Steffen Desch, MD;
Matthias Gutberlet, MD; Gerhard Schuler, MD; Ingo Eitel, MD
on behalf of the AIDA STEMI Investigators

4. Off-label use of IC abciximab
Disclosures
Funding:
Unrestricted grant by Lilly, Germany
University of Leipzig – Heart Center
University of Leipzig, Clinical Trial Centre Leipzig: supported by the Federal
Ministry of Education and Research (BMBF) FKZ 01KN1102
Potential Conflict of Interest:
Research Funding:
Terumo, Lilly. Maquet Cardiovascular, Teleflex Medical
Consulting:
Maquet Cardiovascular, Avidal
Speaker Honoraria:
Lilly, Astra Zeneca, Daiichi Sankyo, Boehringer Ingelheim, Maquet
Cardiovascular, Medicines Company

5. INTRODUCTION
 Randomized studies have consistently shown
that treatment with an adjunctive glycoprotein
IIb/IIIa inhibitor improves coronary
microcirculation and clinical outcome in high-risk
ST-segment elevation myocardial infarction
(STEMI) patients undergoing primary
percutaneous coronary intervention (PCI).
 Intracoronary abciximab bolus administration
results in higher local concentrations and
increased levels of platelet glycoprotein IIb/IIIa
receptor occupancy compared with standard
intravenous application

6. Abciximab IC versus IV
Navarese et al. Platelets 2011;1-8
Background
CICERO 2010
CRYSTAL AMI 2010
Dominguez-Rodriguez 2009
EASY-MI 2010
Iversen 2011
Thiele 2008
5
0
0
0
2
2
271
25
25
53
185
77
7
1
0
0
9
3
263
23
25
52
170
77
33.7%
7.4%
44.8%
14.1%
0.69
0.29 (0.01;7.59)
Not estimable
Not estimable
0.20 (0.04;0.92)
0.66 (0.11;4.05)
Study or Subgroup
Intracoronary abciximabIntravenous abciximab Odds ratio
Events Total Events Total Weight M-H, Fixed 95%
Total (95%)
Total events
636 610 100.0% 0.43 (0.20;0.94)
9 20
Heterogeneity: Chi2 =1.88, df=3 (P=0.60);I2=0%
Test for overall effect: Z=2.11 (P=0.03)
30-day Mortality
M-H, Fixed 95%
Odds ratio
Favors IC Favors IV
0.01 0.1 1 10 100
Favors IC Favors IV
CICERO 2010
EASY-MI 2010
Iversen 2011
Thiele 2008
30-day Myocardial Infarction
3
0
5
0
271
53
185
77
4
0
8
2
263
52
170
77
27.5%
55.5%
17.0%
Study or Subgroup
Intracoronary abciximab Intravenous abciximab Odds ratio
Events Total Events Total Weight M-H, Fixed 95%
Total (95%)
Total events
636
562 100.0% 0.54 (0.23;1.28)
8 14
Heterogeneity: Chi2 =0.58, df=2 (P=0.75);I2=0%
Test for overall effect: Z=1.39 (P=0.17)
M-H, Fixed 95%
Odds ratio
0.01 0.1 1 10 100
0.72 (0.16;3.27)
Not estimable
0.56 (0.18;1.75)
0.19 (0.01;4.13)
586
CICERO 2010
EASY-MI 2010
Iversen 2011
Thiele 2008
30-day Target Vessel Revascularization
9
0
7
0
271
53
185
77
10
0
16
2
263
52
170
77
27.5%
55.5%
17.0%
Study or Subgroup
Intracoronary abciximab Intravenous abciximab Odds ratio
Events Total Events Total Weight M-H, Fixed 95%
Total (95%)
Total events 636
562 100.0% 0.53 (0.29;0.99)
16 28
Heterogeneity: Chi2 =2.58, df=2 (P=0.36);I2=2%
Test for overall effect: Z=2.00 (P=0.05)
M-H, Fixed 95%
Odds ratio
Favors IC Favors IV
0.01 0.1 1 10 100
0.87 (0.35;2.17)
Not estimable
0.38 (0.15;0.94)
0.19 (0.01;4.13)
586

7.  The large, randomized AIDA STEMI (Abciximab
Intracoronary versus intravenously Drug
Application in STEMI) multicenter trial,
intracoronary abciximab application did not
result in a difference in major adverse cardiac
events (MACE) compared with the standard
intravenous route , but the rate of new
congestive heart failure was significantly lower
and there was an observed benefit in the female
subgroup.

8. The Abciximab Intracoronary versus intravenously Drug
Application in ST-Elevation Myocardial Infarction
(AIDA STEMI) trial

9. Methodology
• Primary Study Endpoint:
Composite of all-cause death, reinfarction, new congestive heart
failure at 90 days after randomization
• Secondary Study Endpoints:
- Time to occurrence of combined clinical endpoint
- TIMI-flow post PCI
- ST-segment resolution
- Infarct size by AUC of CK-release
Thiele et al. Circulation 2008;118:49-57
Thiele et al. Am Heart J 2010;159:547-554
Methods

10. 1032 patients randomized
to IC abciximab
1002 patients PCI started
995 patients abciximab
bolus given; PCI
completed
935 patients with 90 day
follow-up
Study Design, Flow, and Compliance
2065 patients with suspected STEMI
- STEMI with symptoms <12 h
- Planned primary PCI
- no contraindication for abciximab
8 technical PCI-problems
7 exclusion criteria detected
UFH 50-70 IU/kg
Aspirin 500 mg, Clopidogrel 600 mg/Prasugrel 60 mg
Abciximab bolus 0.25 mg/kg plus 12 h infusion 0.125 µg/kg/min
1033 patients randomized
to IV abciximab
1001 patients PCI started
993 patients abciximab
bolus given; PCI
completed
932 patients with 90 day
follow-up
64 withdrawal informed consent
32 lost to follow-up
25 incomplete information
62 patients not PCI eligible:
- 46 STEMI not confirmed
- 13 emergency CABG
- 3 exclusion criteria

11. Primary Outcome and Components
IC IV OR 95% CI P
Death/Reinfarction/new
CHF
n/total n (%) 65/935 (7.0) 71/932 (7.6) 0.91 0.91-1.28 0.58
Death
Overalln/total n (%) 42/935 (4.5) 34/932 (3.6) 1.24 0.78-1.97 0.36
Cardiac 35 33
Non-cardiac 7 1
Reinfarction
n/total n (%) 17/935 (1.8) 17/932 (1.8) 1.0 0.51-1.96 0.99
New CHF
n/total n (%) 22/935 (2.4) 38/935 (4.1) 0.57 0.33-0.97 0.04
Results

12. Summary + Conclusions
• This randomized, multi-center, large-scale trial
involving more than 2000 STEMI patients
undergoing primary PCI showed that IC abciximab
bolus administration is safe.
• The IC bolus administration of abciximab does not
add a benefit in comparison to the standard IV
bolus with respect to the combined primary study
endpoint consisting of death, reinfarction, or new
congestive heart failure within 90 days.
• The IC route might be related to reduced rates of
new congestive heart failure.

13. Combined Clinical Endpoint
Time from randomization [days]
Cumulativeeventfreesurvivalfrom
death,reinfarctionand
congestiveheartfailure[%]
p=0.54
Intracoronary Abciximab
Intravenous Abciximab
Thiele et al. Lancet 2012;379:923-31
Background

14. Congestive Heart Failure
p=0.03
Intracoronary Abciximab
Intravenous Abciximab
Time from randomization [days]
Cumulativeeventfreesurvivalof
congestiveheartfailure[%]
Thiele et al. Lancet 2012;379:923-31
Background

15. AIDA-STEMI CMR Substudy
• CMR enables investigation of mechanistic and
pathophysiological effects of intracoronary +
intravenous abciximab application on myocardial
damage and reperfusion injury.
• To determine potential benefits of intracoronary
abciximab application on infarct size, myocardial
salvage, microvascular obstruction and ventricular
function to further evaluate the benefit with respect
to congestive heart failure.
Thiele et al. Am Heart J 2010;159:547-554

16. Study Organization and Study Sites
DSMB:
Uwe Zeymer
Hans-Richard Arntz
Christoph Bode
Karl Wegscheider
Steering Committee:
Holger Thiele
Jochen Wöhrle
Oana Brosteanu
Gerhard Schuler
CRO:
Clinical Trial Center Leipzig
Investigator Initiated Trial
Methods
22 study sites in Germany
8 CMR study sites
CMR core laboratory:
Ingo Eitel (Coordinator)
Josephine Meissner
Henning Sünkel
Holger Thiele

19. RESULTS

20. Patient characteristics
 Patients in the 2 groups had similar baseline
characteristics except for hypertension and
previous bypass surgery.
 All other prescribed drugs and study procedures
were similar for both groups

24. CMR RESULTS
The median time between the index event
and CMR was 3 days (IQR: 2 to 4 days) for both groups

27. Clinical outcome and relationship of CMR
markers and
clinical outcome
 At 12-month follow-up, there were 13 deaths
(3.3%) in the intracoronary and 8 (2.0%) in the
intravenous abciximab groups (hazard ratio:
1.69; 95% confidence interval: 0.69 to 4.11; p=
0.25).
 There were also no significant differences in the
occurrence of nonfatal re-infarctions (p = 0.54)
and congestive heart failure (p = 0.11).

28. Consequently, MACE at 12-month follow-
up were similar (intracoronary 24 [6.2%]
vs. intravenous 29 [7.3%] events; hazard
ratio: 0.84; 95% confidence interval: 0.48
to 1.46; p= 0.53)
Patients in whom MACE occurred had
significantly larger infarcts, less myocardial
salvage, and more pronounced LV
dysfunction

29. Intramyocardial hemorrhage and MO as
markers of severe reperfusion injury were
more frequent in patients with MACE
without reaching statistical significance.

31. Summary + Conclusions
• This largest multicenter CMR study in STEMI patients to
date demonstrates that IC as compared to IV abciximab
did not result in a difference in myocardial damage
and/or reperfusion injury.
• The results of the AIDA STEMI CMR substudy therefore
confirm the lack of difference in the combined endpoint
of death, reinfarction or congestive heart failure of the
AIDA STEMI trial.

32. THANKS