Download AIDA STEMI CMR Substudy LBCT TCT

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
Disclosures
Off-label use of IC abciximab
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
Background
Combined Clinical Endpoint
Cumulative event free survival from
death, reinfarction and
congestive heart failure [%]
p=0.54
Intracoronary Abciximab
Intravenous Abciximab
Time from randomization [days]
Thiele et al. Lancet 2012;379:923-31
Background
Congestive Heart Failure
Cumulative event free survival of
congestive heart failure [%]
p=0.03
Intracoronary Abciximab
Intravenous Abciximab
Time from randomization [days]
Thiele et al. Lancet 2012;379:923-31
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
Methods
Study Organization and Study Sites
Investigator Initiated Trial
22 study sites in Germany
8 CMR study sites
CMR core laboratory:
Ingo Eitel (Coordinator)
Josephine Meissner
Henning Sünkel
Holger Thiele
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
Methods
CMR Protocol
ContrastInjection 1,5
mmol/kg/BW
Bolus Gd i.v.
0
5
Function
4CH+2 CH
10
15
T2
SA
20
25
30
35
Delayed
enhancement
4CH + 2CH + SA
Function
Short axes
40
Time
(min)
Survey
Area at risk +
Hemorrhage
EF, EDV, ESV
late MO + IS
Thiele et al. Am Heart J 2010;159:547-554
Results
Patient Characteristics
IC Abciximab (n=394)
IV Abciximab (n=401)
63 (51-71)
61 (51-71)
287 (73)
316 (79)
161/364 (44)
284/393 (72)
147/391 (38)
87/392 (22)
178/363 (49)
256/399 (64)
157/396 (40)
73/400 (18)
Body mass index (kg/m2); median (IQR)
27.4 (24.9-30.1)
27.3 (24.8-30.5)
Prior myocardial infarction; n/total n (%)
23/393 (6)
25/401 (6)
Prior PCI; n/total n (%)
35/394 (9)
32/401 (8)
Prior CABG; n/total n (%)
2/394 (1)
9/401 (2)
Anterior myocardial infarction; n/total n (%)
180/382 (47)
183/376 (49)
Creatinine clearance (ml/min); median (IQR)
92 (72-120)
96 (74-117)
Symptom-onset - PCI hospital, median (IQR)
Door-to-balloon-time; median (IQR)
164 (108-300)
30 (22-43)
190 (110-335)
29 (22-42)
341/394 (87)
35/394 (9)
11/394 (3)
7/394 (2)
358/401 (89)
24/401 (6)
9/401 (2)
10/401 (3)
Age (years); median (IQR)
Male sex; n (%)
Current Smoking; n/total n (%)
Hypertension; n/total n (%)
Hypercholesterolemia; n/total n (%)
Diabetes mellitus; n/total n (%)
Killip-class on admission; n/total n (%)
1
2
3
4
Results
Area at Risk + Infarct Size
Area at risk
Infarct size
50
Median [IQR] Median [IQR]
35% [25, 48] 35% [26, 48]
Median [IQR] Median [IQR]
16% [9, 25]
17% [8, 25]
p=0.97
Infarct size, %LV
Area at risk, %LV
40
p=0.52
30
20
10
IC abciximab IV abciximab
N=344
N=354
0
IC abciximab IV abciximab
N=385
N=389
Results
Reperfusion Injury
Hemorrhage
Microvascular obstruction
p=0.19
52%
47%
IC abciximab IV abciximab
N=384
N=390
Presence Hemorrhage, %
Presence MO, %
p=0.19
32%
37%
IC abciximab IV abciximab
N=346
N=353
Results
Infarct Size - Subgroups
Baseline variable
N
Mean
Difference
(95% CI)
Infarct size (%LV)
Mean
p-value
Difference
for
IC
IV
abciximab abciximab (95% CI) interaction
All Patients
774
18 (13)
18 (13)
-0.2 (-2.9;1.5)
0.52
Male sex
Female sex
586
188
18 (13)
18 (12)
18 (12)
19 (12)
0.1 (-2.0;2.1)
-1.4 (-4.9;2.1)
0.49
Age < 75 years
Age ≥ 75 years
656
118
18 (13)
18 (12)
18 (12)
21 (12)
0.2 (-1.7;2.1)
-3.1 (-7.6;1.3)
0.46
0.11
Anterior MI
Non-anterior MI
353
388
21 (14)
15 (10)
21 (14)
15 (10)
0.1 (-2.8;3.0)
-0.7 (-2.7;1.3)
0.79
0.42
Killip-class II to IV
Killip-class I
91
683
28 (16)
16 (11)
25 (13)
17 (12)
3.0 (-3.1;9.0)
-0.9 (-2.8; 0.8)
0.50
0.71
TIMI flow post PCI 0 to II
TIMI-flow post PCI III
89
685
24 (14)
17 (12)
19 (9)
18 (13)
4.4 (-0.5;9.3)
-0.9 (-2,8;1.0)
0.96
0.50
Symptom onset-randomization < 3 h
Symptom onset-randomization 3-6 h
Symptom onset-randomization > 6h
334
296
136
17 (13)
19 (13)
18 (12)
15 (12)
20 (13)
20 (12)
2.0 (-0.7;4.6)
-1.6 (-4.5;1.3)
-1.2 (-5.3;2.8)
0.85
0.37
0.60
Thrombectomy
No thrombectomy
187
587
20 (12)
17 (13)
19 (13)
18 (12)
1.4 (-2.2;5.0)
-0.8 (-2.9;1.2)
0.47
0.78
Prasugrel
No prasugrel
173
419
18 (13)
19 (13)
17 (11)
19 (13)
0.6 (-3.0;4.3)
0.2 (-2.2;2.7)
0.84
0.89
-6
-4
-2
IC better
0
2
4
IV better
6
Results
CMR and Outcome
Characteristic
MACE
No MACE
p
Infarct size (%LV)
Median (IQR)
Mean (SD)
n
24 (18 - 31)
24 (14)
50
16 (8 - 24)
18 (12)
718
<0.001
Myocardial salvage index
Median (IQR)
Mean (SD)
n
37 (23 - 55)
43 (26)
44
52 (33 - 69)
53 (26)
644
0.01
Median (IQR)
n
28 / 50 (56%)
0.6 (0 - 2.7)
50
350 / 718 (49%)
0 (0 - 1.6)
718
0.32
0.09
19 / 48 (40%)
228 / 660 (35%)
0.66
Late MO present n (%)
Late MO (%LV)
Hemorrhage present n (%)
Hemorrhage (%LV)
Median (IQR)
n
0 (0 – 2.1)
47
0 (0 - 1.3)
645
0.36
LV ejection fraction (%)
Median (IQR)
Mean (SD)
n
40 (33 - 47)
42 (14)
53
51 (44 - 58)
51 (10)
736
<0.001
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.
Acknowledgement
AIDA STEMI Investigators from 22 sites in Germany
Steering Committee ECG Core Lab
Clinical Trial Center
at University Leipzig
I. Eitel (Chair)
H. Thiele (Chair)
O. Brosteanu (Chair)
A. Baum
J. Wöhrle
P. Neuhaus (Coordinator)
K.P. Rommel
O. Brosteanu
M. Doerschmann
G. Schuler
MRI Core Lab
K. Schosnig
H. Thiele (Chair)
S. Lehmann
Sponsors
I. Eitel (Coordinator) Study Sites
Lilly Germany
Magdeburg: R. Braun-Dullaeus
Leipzig; H. Thiele
H. Sünkel
BMBF
Nürnberg: W. Burkhardt
Bremen: R. Hambrecht
J. Meissner
Bad Berka: B. Lauer
Merseburg: R. Prondzinsky
DSMB
Coburg: H. Rittger
Jena: M. Ferrari
U. Zeymer (Chair) CEC
Villingen-Schwenningen:
Pforzheim: R. Zimmermann
S.
Desch
(Chair)
R. Birkemeyer
H.R. Arntz
Hamburg: K.-H. Kuck
Ulm: J. Wöhrle
H. Thiele
Halle: M. Buerke
C. Bode
Chemnitz: K. Kleinertz
J. Wöhrle
Karlsruhe: C. Schmitt
Regensburg: P. Sick
K. Wegscheider
Bad Oeynhausen: M. Wiemer Kempten: T. Nusser
Bad Neustadt: S. Kerber
Berlin: H. Schühlen
Pirna: C. Axthelm
Suhl: W. Haberbosch