ENDEAVOR I & II Clinical Program

Long Term Follow-Up

Ian Meredith
and
William Wijns
For the ENDEAVOR I and II investigators

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I

Professor Ian Meredith

MBBS, Ph.D, FACC, FRACP
Director of Cardiology
Monash Medical Center, Monash University
and Southern Health Melbourne, Australia

Principal Investigator
On behalf of the ENDEAVOR I Investigators
No conflicts of interest to declare

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR DES System
Key Components
Driver Cobalt Alloy Stent Stent Delivery System

PC Technology Drug: ABT-578

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR
Clinical Program Update
ENDEAVOR
ENDEAVORII Phase
PhaseIIFIM
FIM
N=100
N=100 24
24month
monthresults
results

ENDEAVOR
ENDEAVORIIII Double-blind Randomized
Double-blind RandomizedTrial
Trial
N=1200
N=1200 12
12month
monthresults
results

ENDEAVOR
ENDEAVORIIII Registry
Registry Open
OpenLabel
LabelSafety
SafetyRegistry
Registry
N=300
N=300

ENDEAVOR
ENDEAVORIII
III Confirmatory
ConfirmatoryTrial
Trial
N=436
N=436 vs.
vs.Cypher
Cypher

ENDEAVOR
ENDEAVORIVIV Confirmatory
ConfirmatoryTrial
Trial
N=1548
N=1548 vs.
vs.Taxus
Taxus

E-Five Registry Real -World Performance

Real-World Performanceand
andSafety
Safety
N=8000 Evaluation
Evaluation
All ENDEAVOR trials are analyzed in the same independent core laboratory
Clinical Trial Update, 4 September 2005, ESC Stockholm 2005
 ENDEAVOR I
Phase I FIM Trial
Single
Single DeDe Novo
Novo Native
Native
Coronary
Coronary Artery
Artery Lesions
Lesions (Type
(Type A -B2)
A-B2)
Stent
Stent Diameter:
Diameter: 3.0 -3.5 mm
3.0-3.5 mm
Stent
Stent Length:
Length: 18
18 mm
mm
Lesion
Lesion Length:
Length: <<15
15 mm
mm
Pre -dilatation required
Pre-dilatation required
N = 100 patients
8 sites
Australia and New Zealand
Clinical / MACE
30d 4mo 9mo 12mo 2yr 3yr 4yr 5yr
Angiography / IVUS

Primary
PrimaryEndpoints:
Endpoints: MACE
MACEat at30
30days
daysand
andlate
lateloss
loss(QCA)
(QCA)atat44mont hs
months
Secondary
SecondaryEndpoints:
Endpoints:TVFTVFand
andTLR
TLRatat99months,
months,latelateloss
lossat
at12
12mo nths
months
Dual
Dualantiplatelet
antiplatelettherapy
therapyfor
for33months,
months,1010µµg
g ABT -578 per
ABT-578 permm
mmstent
stentlength
length

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I
Clinical, QCA and IVUS results to 12 months

30 Days 4 Months 12 Months

n=100 n=98 n=98
MACE 1% 2% 2%
TLR 1% 2% 2%
TVF 1% 2% 2%
In-stent LL n/a 0.33mm 0.61mm
In segment LL n/a 0.21mm 0.43mm
In-stent ABR n/a 2.1% 5.4%
Diameter stenosis n/a 14.6% 22.4%
Neointimal volume n/a 6.1mm3 14.2 mm3

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I
Clinical outcomes at 24 months

• With the observed increase in late loss from 4 to

12 months would clinical efficacy be preserved
at 2 years ?

• Would the safety profile of the ENDEAVOR DES

alter with this longer term follow-up ?

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I
Patient Flowchart

100 Patients Enrolled

4 Month 12 Month 24 Month

Follow-Up Follow-Up Follow-Up

Clinical F/U Clinical F/U Clinical F/U

100 Patients 98 Patients 97 Patients

Angiographic Angiographic
F/U 97 Patients F/U 91 Patients

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I
Clinical Events to 2 Years
0 - 30 1 - 12 12 - 24 0 - 24
Days Months Months Months
n=100 n=98 n=97 n=97
MACE 1% 1% 1% 3%
Death 0 0 1%# 1%#
MI (all) 1% 0 0 1%
Q-wave 0 0 0 0
Non Q-wave 1%* 0% 0 1%*
TLR 1% 1% 0 2%
TVR (non-TL) 0 0 2% 2%
TVF 1% 1% 2% 4%

* Stent Thrombosis at 10-days

#Non cardiac death – metastatic melanoma Clinical Trial Update, 4 September 2005, ESC Stockholm 2005
 Survival Free from Target Lesion
Revascularization
Event-Free Survival ±1.96 SE
100%

90% 98.0%

80%
Freedom From TLR

70%

60%

50%

40%

30%

20%

10%

0%
0 90 180 270 360 450 540 630 720
Time After Initial Procedure (days)

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I
Summary of Clinical Events
1 Non-Q wave MI, Subacute Closure/Stent Thrombosis
10 days post-procedure
• TLR – PTCA 11 days post-procedure; TLR-CABG 17 days post-
procedure

1 non-cardiac death @ 379 days post-procedure

• Cause of death: metastatic melanoma
1 TVR 409 days post-procedure
• PCI for mid LAD lesion, remote target vessel revascularization,
study stent patent

1 TVR – CABG 515 days post-procedure

• Study stent patent mid LAD, 80% ostial lesion
required CABG with a LIMA on the proximal LAD

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I
Safety Profile
No Stent Thrombosis After 10 Days

ENDEAVOR I

N = 100
1.0%

1 2 3 10 11 12 30 100 200 360 400 500 600 720

Days

Defined as angiographic thrombus or subacute closure within the stented vessel at the time
of the clinically driven angiographic restudy for documented ischaemia (chest pain and
ECG changes).
Any death not attributed to a non-cardiac cause within the first 30 days is considered a
surrogate for stent thrombosis in the absence of documented angiographic stent patency.

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR I
Summary

• 97% clinical follow-up to 2 years

• Sustained safety and efficacy
¨ 97% MACE free at 24 months
¨ 2% TLR by 12 months
¨ No further TLR to 24 months
¨ No stent thrombosis after 10 days

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR II
A Randomized Trial to Evaluate the Safety and Efficacy of the
Medtronic AVE ABT-578 Eluting Driver Coronary Stent in De Novo
Native Coronary Artery Lesion

12 month follow-up

J. Fajadet, W. Wijns and R. Kuntz

Principal Investigators
for the ENDEAVOR II trial
No conflicts of interest to declare

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR II
Randomized, Double-Blind Trial Design
Single
Single De
De Novo
Novo Native
Native Coronary
Coronary Artery
Artery Lesions
Lesions
Stent
Stent Diameters:
Diameters: 2.25 -3.5 mm
2.25-3.5 mm
Stent
Stent Lengths: 18-30 mm (8/9 mm bailout)
Lengths: 18 - 30 mm (8/9 mm bailout)
Lesion Length: 14 - 27
Lesion Length: 14-27 mm mm
Pre -dilatation required
Pre-dilatation required
n=1,200 patients
ENDEAVOR
ENDEAVOR Stent
Stent 72 sites Driver
Driver Stent
Stent
Active
Active Arm
Arm Europe, Asia Pacific, Israel, Control
Control Arm
Arm
n=600
n=600 New Zealand and Australia n=600
n=600
Clinical / MACE
30d 6mo 8mo 9mo 12mo 2yr 3yr 4yr 5yr
Angiography / IVUS
Angio N = first 600
IVUS N = first 300
IVUS for overlapping stents

Primary
Primary Endpoint:
Endpoint: TVFTVF (cardiac
(cardiac death,
death, MI,
MI, TVR)
TVR) at
at 99 months
months
Dual
Dual antiplatelet
antiplatelet therapy
therapy for
for 33 months
months
10 µµg
10 g ABT -578 per
ABT-578 per mm
mm stent
stent length
length
Clinical Trial Update, 4 September 2005, ESC Stockholm 2005
 ENDEAVOR II
Clinical Outcome
TVF* MACE
p<0.0005 p=0.0001

15.1% 14.4%

8.0% 7.3%
Rate

Driver Endeavor Driver Endeavor

TVF * = Primary Endpoint at 9 Month Follow-Up

*Target Vessel Failure is a composite of target vessel revascularization,
Q- or non Q-wave MI, or cardiac death
Clinical Trial Update, 4 September 2005, ESC Stockholm 2005
 Pivotal DES Trials

DES arm (1:1) SIRIUS TAXUS IV ENDEAVOR

Number of patients 533 662 598

Clinical Outcome
Target Vessel Failure [%] 8.6 7.6 8.0
MACE [%] 7.1 8.5 7.3

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 Pivotal DES Trials

DES arm (1:1) SIRIUS TAXUS ENDEAVOR

Number of patients 533 662 598

Clinical Outcome
Target Vessel Failure [%] 8.6 7.6 8.1
MACE [%] 7.1 8.5 7.4

Angiographic Metrics
In-stent Late Loss [mm] 0.17 0.39 0.62
In segment Late Loss [mm] 0.24 0.23 0.36

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR II
Clinical outcome at 12 months

• Given the observed late loss, will these safety and

efficacy results be maintaind at 1 year?

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR II
Patient Flowchart
Trial Sample
N=1197

Randomized
ENDEAVOR Driver
N=598 N=599

Clinical F/U Clinical F/U Clinical F/U Clinical F/U

(9 mo) (12 mo) (9 mo) (12 mo)
591/598 582/598 591/599 583/599
98.8% 97.3% 98.7% 97.3%

Follow-up from 9-12 mo was captured via phone call. Clinical Trial Update, 4 September 2005, ESC Stockholm 2005
 ENDEAVOR II
Clinical Events to 12 months
0-9 9 - 12 0-9 9 - 12
Months Months Months Months
ENDEAVOR ENDEAVOR Driver Driver
MACE 7.3% 1.5% 14.4% 1.5%
Death 1.2% [7*] 0.2% [1] 0.5% [3] 0.2% [1]
MI (all) 2.7% 0% 4.0% 0%
Q-wave 0.3% 0% 0.9% 0%
Non Q-wave 2.4% 0% 3.1% 0%
TLR 4.6% 1.4% 11.8% 1.4%
TVR (non-TL) 1.5% 0.3% 2.2% 0.3%
TVF 8.0% 1.9% 15.1% 1.9%
* 2 of 7 deaths non-cardiac (1 lung cancer, 1 cerebral hemorrhage)

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR II
TLR-Free Survival at 360 Days
100% 94.0%
90%

86.9%
Freedom from TLR

80%

70%
p<0.001, log rank

60%

50% (Event Free ±1.5 SE)

40%

30%

20%

10%
DRIVER ENDEAVOR
0%
0 30 60 90 120 150 180 270 300 330 360 330 360

Time after Initial Procedure (days)

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR II
TVF-Free Survival at 360 Days

100%
90.2%
90%

80%
83.4%
Freedom from TVF

70%
p<0.001, log rank
60%
(Event Free ±1.5 SE)
50%

40%

30%

20%

10%
Driver ENDEAVOR
0%
0 30 60 90 120 150 180 270 300 330 360 330 360
Time after Initial Procedure (days)

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005

 ENDEAVOR II
Stent Thrombosis Timing
No Stent Thrombosis After 14 Days *
Driver

1.2% (7)

1 2 3 12 13 14 30 100 150 200 270 300 325 360 Days

ENDEAVOR

0.5% (3) 0.5%(3)

Defined as angiographic thrombus or subacute closure within the stented vessel at the time
of the clinically driven angiographic restudy for documented ischaemia (chest pain and ECG changes).
Any death not attributed to a non-cardiac cause within the first 30 days is considered a surrogate for
stent thrombosis in the absence of documented angiographic stent patency.

* Through 12 months of follow-up Clinical Trial Update, 4 September 2005, ESC Stockholm 2005
 Conclusions
ENDEAVOR I and II

• The Endeavor stent is highly deliverable

• The need for repeat intervention is low and maintained
• No stent thromboses were observed beyond 10 days
• These clinical data confirm that the Endeavor stent is a
safe, effective and durable treatment option for patients
undergoing PCI in the DES era

Clinical Trial Update, 4 September 2005, ESC Stockholm 2005