Transcript ABOARD - Clinical Trial Results

Angioplasty to Blunt the rise Of troponin
in Acute coronary syndromes Randomized
for an immediate or Delayed intervention
A Multicenter Randomized Trial of
Immediate Versus Delayed Invasive Strategy
in Patients with Non-ST Elevation ACS
G. Montalescot, on behalf of the ABOARD investigators
Funded by the Programme Hospitalier de Recherche Clinique (French Ministry of Health)
Sponsored by Assistance Publique-Hopitaux de Paris (AP-HP)
Led by the A.C.T.I.O.N. group (Academic Research Organization)
Coordinating Center: Pitié-Salpêtrière University Hospital
Data Management and Statistics: URC Lariboisière University Hospital
Additional support from Eli-Lilly
G. Montalescot, disclosure: research grant, consulting or speaker fee from BMS, Boston
scientific, Cordis, Daiichi Sankyo, Eli Lilly, GSK, SAG, MSD, The Medicines Company,
Medtronic, Novartis, Portola, Schering.
Preliminary Results
Background
 Randomized trials have demonstrated that an
invasive strategy is superior to a conservative
strategy in NSTE-ACS
 The optimal timing of intervention remains a
matter of debate
 A “primary PCI” approach of NSTE-ACS has
not been tested yet
Preliminary Results
Time to catheterization (hrs)
FRISC 2 (1999)
TRUCS (2000)
EARLY
96
48
LATE
408
120
TIMI-18 (2001)
VINO (2002)
RITA 3 (2002)
ELISA (2003)
22
6
48
6
79
1464
1020
50
ISAR-COOL (2003)
ICTUS (2005)
TIME-ACS (2008)
3
23
14
86
283
50
Immediate
Next morning
ABOARD (2009)
Preliminary Results
Study objective
To determine whether immediate
intervention (“primary PCI strategy”) is
superior to delayed intervention (“next day
strategy”) in patients with moderate-to-high
risk (TIMI score > 3) non-ST segment
elevation ACS.
Preliminary Results
ABOARD study design
NSTE-ACS
2 of 3 Criteria: Ischemic symptom, ST-T change, troponin rise
with TIMI score > 3
IVRS RANDOMIZATION
Immediate cath
Next day cath
All PCIs on abciximab
1-month Follow-up
Preliminary Results
Correlation Between Elevat
and Long-term M
Troponin during hospitalization
% mortality at 42 days
8
ACS
7.5%
20
6
15
6.0%
« The preferred biomarker for
myocardial necrosis is
cardiac troponin »
4
3.4
%
3.7%
10
2
1.0
%
0
<0.4
5
1.7
%
<1.0
<2.0
<5.0 <9.0
9.0
0
Cardiac Troponin 1 (ng/ML)
1. Antman EM, et al. N Engl J Med. 1996; 335: 1342-1349.
2. Alexander JH et al. Circulation. 1999; Suppl 1:1-629.
2007
Antman EM et al – NEJM 1996
Nienhuis MB et al - CCI 2008
ALL
1.35 (1.13-1.60)
PCI
Preliminary Results
Outcomes
 Primary
−
MI: defined as the peak of troponin I during
hodpitalization
 Secondary
1.
Death (any), new MI (CK-MB) or urgent
revascularization (PCI or CABG)
2.
Death, new MI, urgent revascularization or
recurrent ischemia
3.
Individual parameters
Preliminary Results
Statistical Analysis
Study Power: 352 patients: 80% power to
detect an effect size equal to 0.3
Randomization: Central 24 hour IVRS
Analysis: Intention to treat; Tests: Mann-
Follow-up: 100%
Density
Whitney test for non-gaussian quantitative
parameters, Chi-square or Fisher’s exact
probability tests for qualitative parameters .
Troponin levels
Preliminary
Results
Top-10 Recruiting Centers
1- G. Montalescot – Pitié, Paris
2- G. Cayla – Nimes
3- S. Elhadad – Lagny
4- H. Lebreton – Rennes
5- F. Leclercq – Montpellier
6- F. Duclos – Argenteuil
7- J.L. Dubois-Randé – Créteil
8- P.G. Steg – Bichat, Paris
9- L. Payot – Montreuil
10- P. Henry – Lariboisière, Paris
Preliminary Results
Baseline Characteristics
Characteristic
Age, mean ± sd, y
Female sex, %
Weight, mean ± sd, kg
Current smoking, %
Diabetes mellitus, %
Previous CABG, %
Previous MI, %
Previous PCI, %
Previous Stroke, %
Cardiac Insufficiency, %
Immediate
Delayed
(N=175)
(N=177)
65 ± 12
27.4
77 ± 16
32.0
21.7
5.1
16.6
24.6
5.2
4.0
65± 12
29.4
76 ± 15
33.9
32.2
6.8
18.6
30.5
4.5
4.0 Results
Preliminary
Index ACS event
Entry criteria, (%)
Ischemic symptom
ST-T segment changes
Elevated Troponin I
Immediate Delayed
(N=175)
(N=177)
98.2
69.7
75.4
97.7
76.8
72.9
95.4
22.9
95.5
30.5
TIMI score, (%)
>3
>5
Preliminary Results
In-hospital medications
Immediate
Delayed
(N=175)
(N=177)
Aspirin, (%)
99.4
100
Clopidogrel, (%)
96.6
98.9
660 ± 268
663 ± 267
111 ± 40
111 ± 39
Abciximab, (%)
65.1
57.4
Unfractionated heparin only, (%)
5.1
3.4
Low Molecular Weight Heparin only, (%)
68.6
67.2
Both UFH and LMWH, (%)
22.9
28.8
Neither UFH nor LMWH, (%)
2.9
0.6
Beta-blocker, (%)
87.4
85.3
Statin, (%)
94.3
95.5
ACE inhibitor or ARB, (%)
84.5
80.2
Loading dose, mean ± sd, mg
Maintenance dose, mean ± sd, mg
Preliminary Results
Time to catheterization (hrs)
IMMEDIATE
96
48
22
DELAYED
408
120
79
VINO (2002)
RITA 3 (2002)
ELISA (2003)
6
48
6
1464
1020
50
ISAR-COOL (2003)
ICTUS (2005)
TIME-ACS (2008)
ABOARD (2009)
median (IQR), hr.min
3
23
14
86
283
50
1.10
20.48
FRISC 2 (1999)
TRUCS (2000)
TIMI-18 (2001)
(0.51-2.03)
(17.30-24.36)
Preliminary Results
Interventions
IMMEDIATE
DELAYED
87.4
81.8
Left main trunk, (%)
4.1
7.3
Left anterior descending artery, (%)
48.6
45.0
Circumflex artery, (%)
24.7
29.1
Right coronary artery, (%)
24.7
25.2
Coronary bypass graft, (%)
2.1
2.0
Percutaneous Coronary Intervention, (%)
80.1
69.5
Stent (at least one), (% of PCI)
94.0
96.2
DES (at least one), (% of PCI)
47.9
55.2
1.2 ± 0.9
1.2 ± 1.0
11.0
11.3
Radial access (%)
Culprit artery
Number of stents/patient, mean±sd
CABG surgery, (%)
Preliminary Results
Primary EP (peak of troponin I)
0.02
0.04
0.06
0.08
immediate group
delayed group
Median, IQR
2.1 (0.3-7.1) p = 0.70
1.7 (0.3-7.2)
0.00
Density
0.10
0.12
0.14
Distribution curves of the peaks values of troponin
Peakinvalues
of troponin I in the 2 groups
the immediate and delayed groups
0
20
40
60
80
100
Troponin I (ng/mL)
Preliminary Results
Composite Ischemic Endpoints at 1 month
% 25
20
15
Immediate
Delayed
P=0.94
P=0.31
10
5
0
Death / MI / UR
Death / MI / UR / RI
Key secondary EP
Preliminary Results
Individual Ischemic Endpoints at 1 month
% 20
P=0.08
Immediate
Delayed
18
16
14
12
10
8
6
4
2
0
P=0.09
P=0.32
P=0.57
P=0.28
ch
G
R
ec
Is
A
B
C
rg
U
U
rg
as
ev
R
rg
U
PC
I
c
I
M
D
ea
th
P=0.62
Preliminary Results
Safety outcomes at 1 month
Immediate
Delayed
P
Major bleeding at 1 month, (%)
4.0
6.8
0.25
Non-CABG related major bleeding,
2.3
5.1
0.26
CABG-related major bleeding
1.7
1.7
1.00
Transfusion > 2 units
3.4
5.6
0.32
Transfusion > 5 units
1.1
1.1
1.00
2.9
4.5
0.41
Non-CABG thrombocytopenia, (%)
2.3
4.0
0.54
Post-CABG thrombocytopenia, (%)
0.6
0.6
1.00
Thrombocytopenia at 1 month, (%)
Preliminary Results
Sites of Major Bleedings
n
1- Gastro-Intestinal
4
2- Puncture-related
4
3- Hemopericardium
2
4- Intracranial
1
5- Epistaxis
1
6- Hematoma (not puncture-related)
1
unknown
7
One patient had 2 bleeding events
Preliminary Results
Subgroup analysis (primary EP)
Median differences and Hodges-Lehmann CI for the primary end point (peak of troponin)
Immediate better
Delayed better
Preliminary Results
Hospital stay
Immediate
55
Median, IQR, hrs
( 30; 98)
Delayed
77
Median, IQR, hrs
( 49; 145)
P<0.001
Preliminary Results
Conclusions
A « primary PCI strategy » in NSTE-ACS (compared
with a rapid intervention on the next day):
− is feasible, but does not reduce the risk of MI (primary
outcome)
− is not associated with significant differences in other efficacy
or safety outcomes
− does not benefit to a particular subgroup of patients
− shortens significantly hospital stay
Preliminary Results
Thank you
Preliminary Results