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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
ISAR-CABG:Randomized, Superiority Trial of
Drug-Eluting-Stent and Bare Metal Stent in Safenous Vein Graft Lesions
Disclosure Statementof Financial Interest
Lecture fees from Abbott Vascular
Background
Years After RandomizationPatients at Risk
SESBMS
24862472
18911639
1099902
921773
682621
491395
0
10
20
30
40
50
Sirolimus-eluting stent
0 1 2 3 4 5
Bare metal stent
Pro
ba
bili
ty o
f D
ea
th,
MI
an
d R
ein
terv
en
tion
, %
HR 0.43 (0.34, 0.54)14 Trials, 4958 pts
DES are more effective and as safe as their BMS
predecessors in native coronary artery lesions
Kastrati …Schömig, NEJM 2007
HR 0.46 (0.38, 0.55)5 Trials, 3513 pts
Stone …Leon, NEJM 2007
DES vs. BMSin Saphenous Vein Graft Lesions
Vermeersch et al., JACC 2007
DELAYED RRISC TrialN=75
months
24
30
0
10
20
30
40
50%
TLR
P=.55
Survival
SES BMS
All-cause Death Target Lesion Revascularization
Cardiac death7% (PES) vs. 13% (BMS)
HR 0.62 [0.15-2-6]; P=0.51
DES vs. BMSin Saphenous Vein Graft Lesions
Brilakis et al., JACC Intv 2011
SOS TrialN=80
Objective of the ofISAR-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 Munich1.Med. Klinik, Klinikum rechts der Isar, MunichHerzzentrum Bad Krozingen, Bad KrozingenBad Segeberger Kliniken, Bad Segeberg
Germany
Inclusion criteriaPatients 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 criteriaCardiogenic shock Target lesion located in arterial graftsMalignancies with life expectancy <1 yearAllergies to study medication
Patient Selection
Composite of
death,
myocardial infarction
ischemia-related target lesion revascularization
at 1-year post index PCI
Primary Endpoint
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)
DES(Cypher/Taxus/BP Sirolimus)
n=303
BMS
n=307
610 patients with de novo SVG lesions
Is Drug-Eluting Stenting Associated With Improved Results inCoronary Artery Bypass Grafts?
ISAR-CABG
6 to 8-month repeat angiogram (encouraged)
12-month clinical follow-up
serial CK+ CKMB
measurements
600 mg Clopidogrel
PCIASS 500 mg
0
repeat angiography
clinicalfollow-up
6-8 mo. 12 mo.
Follow-Up Protocol
30 d
clinicalfollow-up
Clopidogrel 2x75 mg/day until discharge 75 mg at least 6 months after index PCI
Aspirin 200 mg/d indefinitely
DESn=303
BMSn=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
DESn=303
BMSn=307
Clinical presentation, %
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
LV ejection fraction, % 49.2±12.2 49.5±13.8
Baseline clinical characteristics, II
Angiographic characteristics
DESn=386
BMSn=385
Recipient vessel, %
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
36
26
20
18
DES%
>75%50%-75%25%-50%
Distribution of SVGDegeneration Score
< 25%
34
27
20
19
BMS%
16
12
26
28
144
DES%
medialproximalcoronary
Distribution of Lesion Locationwithin the SVGs
aortal
BMS%
distal diffuse
18
10
2326
17
6
5 53 4
17 17
75 74
0 267
93 90
100
60
20
%
100
60
20
%
Distribution of TIMI Flow Rates
DES BMS DES BMS
Prior to PCI After PCI
TIMI 3 TIMI 2 TIMI 1 TIMI 0
30-Day Clinical Outcomes
0.7 0.3
2.0 2.6
1.0 0.6
4.65.9
0
5
10
15
20
%
BMS
DES
P=.57 P=.66 P=.07 P=.05
Cardiac death Myocardial infarction
* No TLR occurred and only 1 pt (DES) died suddenly (probable stent thrombosis) during 30-day follow-up
MACE*All-cause death
Months After Randomization
Cu
mu
lativ
e In
cid
en
ce (
%)
0
10
20
30
40
50
0 1 2 3 4 5 6 7 8 9 10 11 12
Primary Endpoint: Death/MI/TLR
22.1%
15.4%
P=.03RR 0.65 [0.45-0.96]
BMS
DES
All-cause Death
Months After Randomization
0
10
20
30
40
50
0 1 2 3 4 5 6 7 8 9 10 11 12
Cu
mu
lativ
e In
cid
en
ce (
%)
4.7%
5.2%
P=.82RR 1.09 [0.52-2.25]
BMS
DES
Months After Randomization
0
10
20
30
40
50
0 1 2 3 4 5 6 7 8 9 10 11 12
Cu
mu
lativ
e In
cid
en
ce (
%)
Myocardial Infarction
6.0%
4.2%
P=.27RR 0.66 [0.32-1.37]
BMS
DES
Death or Myocardial InfarctionC
um
ula
tive
Inci
de
nce
(%
) P=.27RR 0.75 [0.45-1.26]
BMS
DES
Months After Randomization
0
10
20
30
40
50
0 1 2 3 4 5 6 7 8 9 10 11 12
10.9%
8.5%
Definite/Probable Stent Thrombosis
Months After Randomization
0 1 2 3 4 5 6 7 8 9 10 11 12
0
1
2
3
4
5
Cu
mu
lativ
e In
cid
en
ce (
%) P=.99
RR 1.01 [0.14-7.18]BMS
DES
0.7%
0.7%
Target Lesion Revascularization
0
10
20
30
40
50
0 1 2 3 4 5 6 7 8 9 10 11 12
Cu
mu
lativ
e In
cid
en
ce (
%) P=.02
RR 0.52 [0.30-0.90]BMS
DES
13.1%
7.2%
Months After Randomization
Target Vessel Revascularization
7.2
13.1
0
5
10
15
20
%
BMSDES
TLR
11.5
17.8
0
10
20
%
TVRP=.02
RR 0.52 [0.30-0.90]P=.03
RR 0.61 [0.39-0.95]
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.