Transcript Folie 1 - Cardiol

ISAR-CABG:
Randomized, Superiority Trial of
Drug-Eluting-Stent and Bare Metal Stent in
Safenous Vein Graft Lesions
J. Mehilli, MD,
G. Richard, F-J. Neumann, S. Massberg, K-L. Laugwitz, J. Pache,
J. Hausleiter, I. Ott, M. Fusaro, T. Ibrahim, A. Schömig, A. Kastrati
Deutsches Herzzentrum & 1st Med. Klinik rechts der Isar,
Technische Universität Munich, Germany
Disclosure Statement
of Financial Interest
Lecture fees from Abbott Vascular
Background
DES are more effective
and as safe as their BMS
predecessors in native
coronary artery lesions
Probability of Death,
MI and Reintervention, %
50
14 Trials, 4958 pts
HR 0.43 (0.34, 0.54)
5 Trials, 3513 pts
HR 0.46 (0.38, 0.55)
40
30
20
10
Sirolimus-eluting stent
Bare metal stent
0
0
Patients at Risk
SES
2486
BMS
2472
1
1891
1639
2
3
Years After Randomization
1099
902
921
773
Kastrati …Schömig, NEJM 2007
4
5
682
621
491
395
Stone …Leon, NEJM 2007
DES vs. BMS
in Saphenous Vein Graft Lesions
DELAYED RRISC Trial
N=75
TLR
Survival
50
P=.55
%
40
30
30
24
20
10
0
months
SES
BMS
Vermeersch et al., JACC 2007
DES vs. BMS
in Saphenous Vein Graft Lesions
SOS Trial
N=80
All-cause Death
Target Lesion Revascularization
Cardiac death
7% (PES) vs. 13% (BMS)
HR 0.62 [0.15-2-6]; P=0.51
Brilakis et al., JACC Intv 2011
Objective of the of
ISAR-CABG Trial:
…to compare the efficacy of drug-eluting stents
against bare metal stents – in a trial powered for
clinical events
Participating Centers
Deutsches Herzzentrum Munich
1. Med. Klinik, Klinikum rechts der Isar, Munich
Herzzentrum Bad Krozingen, Bad Krozingen
Bad Segeberger Kliniken, Bad Segeberg
Germany
Patient Selection
Inclusion criteria
Patients with ischemic symptoms or
evidence of myocardial ischemia in the
presence of ≥50 % de novo stenosis
located in saphenous vein grafts
Informed, written consent
Exclusion criteria
Cardiogenic shock
Target lesion located in arterial grafts
Malignancies with life expectancy <1 year
Allergies to study medication
Primary Endpoint
Composite of
death,
myocardial infarction
ischemia-related target lesion revascularization
at 1-year post index PCI
Secondary Endpoints
All cause mortality
Myocardial infarction
Ischemia-related target lesion revascularization
Incidence of definite/probable stent thrombosis
at 1-year post index PCI
Sample Size Calculation
Hypothesis:
Drug-eluting stent (DES) is superior to bare metal stent
(BMS) in terms of major adverse cardiac events
Assumptions:
Incidence of primary endpoint in BMS group of 30%
Reduction of MACE with DES of 33%
Power of 80%
-level of 0.05
Total number of patients needed: 600
(accounting for possible losses at follow-up)
ISAR-CABG
Is Drug-Eluting Stenting Associated With Improved Results in
Coronary Artery Bypass Grafts?
610 patients with de novo SVG lesions
DES
(Cypher/Taxus/BP Sirolimus)
n=303
BMS
n=307
6 to 8-month repeat angiogram (encouraged)
12-month clinical follow-up
Follow-Up Protocol
600 mg Clopidogrel
PCI
ASS 500 mg
0
serial CK
+ CKMB
measurements
Clopidogrel
Aspirin
30 d
clinical
follow-up
6-8 mo.
repeat
angiography
2x75 mg/day until discharge
75 mg at least 6 months after index PCI
200 mg/d indefinitely
12 mo.
clinical
follow-up
Baseline clinical characteristics
DES
n=303
BMS
n=307
Age, years
71.4±9.0
71.5±9.3
Female, %
13
16
Art. hypertension, %
71
73
Diabetes, %
37
35
Current smoker, %
8
6
Hyperlipidemia, %
88
86
SVG age, years
13.8±5.5
13.5±5.1
History of MI, %
56
55
Baseline clinical characteristics, II
DES
n=303
BMS
n=307
acute MI
17
13
unstable angina
21
27
stable angina
62
60
Multivessel disease, %
98
99
Multilesion PCI, %
24
22
>1 SVGs treated/patient, %
4.0
3.6
49.2±12.2
49.5±13.8
Clinical presentation, %
LV ejection fraction, %
Angiographic characteristics
DES
n=386
BMS
n=385
LAD/diagonal
32.0
31.0
LCx/marginal
35.0
36.0
RCA/PDA
33.0
33.0
Vessel size, mm
3.36±0.67
3.38±0.73
Total stented length, mm
26.8±15.4
27.5±17.7
Recipient vessel, %
Distribution of SVG
Degeneration Score
< 25%
25%-50%
50%-75%
>75%
DES
%
BMS
%
18
19
34
36
20
20
26
27
Distribution of Lesion Location
within the SVGs
aortal
DES
%
coronary
4
14
proximal
medial
distal
6
16
17
diffuse
BMS
%
18
12
10
28
26
26
23
Distribution of TIMI Flow Rates
After PCI
Prior to PCI
100
100
%
%
60
74
75
60
90
93
20
20
17
17
3
5
4
5
6
0
DES
BMS
DES
TIMI 3
TIMI 2
TIMI 1
7
2
BMS
TIMI 0
30-Day Clinical Outcomes
20
%
P=.57
P=.66
P=.07
P=.05
DES
15
BMS
10
5.9
4.6
5
0.7
1.0
2.0
0.3
2.6
0.6
0
All-cause death
Cardiac death
Myocardial infarction
MACE*
* No TLR occurred and only 1 pt (DES) died suddenly (probable stent thrombosis) during 30-day follow-up
Primary Endpoint: Death/MI/TLR
50
Cumulative Incidence (%)
DES
P=.03
RR 0.65 [0.45-0.96]
BMS
40
30
22.1%
20
15.4%
10
0
0
1
2
3
4
5
6
7
8
9
Months After Randomization
10
11
12
All-cause Death
50
Cumulative Incidence (%)
DES
40
P=.82
RR 1.09 [0.52-2.25]
BMS
30
20
10
5.2%
4.7%
0
0
1
2
3
4
5
6
7
8
9
Months After Randomization
10
11
12
Myocardial Infarction
50
Cumulative Incidence (%)
DES
P=.27
RR 0.66 [0.32-1.37]
BMS
40
30
20
10
6.0%
4.2%
0
0
1
2
3
4
5
6
7
8
9
Months After Randomization
10
11
12
Death or Myocardial Infarction
50
Cumulative Incidence (%)
DES
P=.27
RR 0.75 [0.45-1.26]
BMS
40
30
20
10.9%
10
8.5%
0
0
1
2
3
4
5
6
7
8
Months After Randomization
9
10
11
12
Definite/Probable Stent Thrombosis
5
Cumulative Incidence (%)
DES
4
P=.99
RR 1.01 [0.14-7.18]
BMS
3
2
0.7%
1
0.7%
0
0
1
2
3
4
5
6
7
8
9
Months After Randomization
10
11
12
Target Lesion Revascularization
50
Cumulative Incidence (%)
DES
P=.02
RR 0.52 [0.30-0.90]
BMS
40
30
20
13.1%
10
7.2%
0
0
1
2
3
4
5
6
7
8
Months After Randomization
9
10
11
12
Target Vessel Revascularization
TLR
TVR
P=.02
RR 0.52 [0.30-0.90]
P=.03
RR 0.61 [0.39-0.95]
20
20
%
%
15
17.8
13.1
11.5
10
10
7.2
5
0
0
DES
BMS
Summary
Out to 12 months drug-eluting stents are superior
to bare metal stents in a large-scale study powered
for clinical endpoints.
The need for repeat revascularizations was
reduced by ~50% with DES as compared to BMS.
DES were comparable to BMS regarding safety
parameters – stent thrombosis, death or MI.