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.