EFive Registry Primary Endpoint Results

1
E-Five RegistryPrimary Endpoint Results
Prospective, Multicenter RegistryPI Chaim
Lotan, Ian Meredith and Martin Rothman

• Martin Rothman on behalf of theE-Five
  Investigators
• Conflicts none

2
E-Five Registry
Rationale for Registries

• Advantages
• Clinical outcomes from the real world versus RCTs
  necessary to determine device safety and efficacy
  
• Limitations
• Reduced monitoring versus RCTs
• Lost to follow up
• Potential under reporting
• The E-Five registry was designed to gain insight
  into clinical outcomes with the Endeavor DES in a
  real world patient population

3
E-Five Registry
Prospective, Multicenter RegistryPI Chaim
Lotan, Ian Meredith and Martin Rothman
Single and Multiple Coronary Artery Lesions Stent
Diameters 2.25-4.0 mm Stent Length 8/9-30 mm
N 8,000 patients 200 sites Europe, Asia
Pacific, Israel, New Zealand, South America
Clinical/MACE
30d
6mo
2yr
12mo
Primary Endpoint MACE at 12 months Secondary
Endpoints MACE at 30 days and 6 mo, Stent
thrombosis, procedure success rate device
success rate lesion success rate Drug Therapy
ASA and Clopidogrel 3 monthsZotarolimus Dose
10 ?g per mm stent length
Limited number of centers.
4
E-Five Registry
Design

• Definitions
• MACE Death, MI, emergent bypass, TLR
• Stent Thrombosis cardiac death lt30 days post
  procedure or angiographic/autopsy confirmation of
  thrombus
• Additional adjudication using ARC
  definite/probable definition for ST
• Myocardial Infarction 2x ULN CK including CKMB
  (confirmation by enzymes)
• 2 year follow up in 2000 patients

5
E-Five Registry
Data System and Quality Control

• Clinical Event Committee
• Cardialysis (Rotterdam, The Netherlands)
• Independent adjudication of all reported MACE and
  Stent Thrombosis (protocol and ARC
  definite/probable) events
• Data Monitoring
• 10 monitoring aimed at detecting underreporting
  (CRO and Medtronic)
• Random patient selection
• Electronic Data Collection

6
E-Five Enrollment
8314 patients enrolled
1 25
100 300
gt 1000
300 1000
25 100
7
E-Five Registry
Patient Demographics
n 8314 Patients
Male ()
Age (years)
Prior MI ()
Non Q-wave MI
Q wave MI
Prior PCI ()
Prior CABG ()
Diabetes Mellitus ()
Acute coronary syndrome ()
Recent MI () lt72hrs
Unstable Angina ()
Mod/severe renal impairment ()
8
E-Five Registry
Procedure Characteristics
44.7
9
E-Five Registry
Complex Subsets
10
E-Five Registry
Clinical Outcomes to 12 months per protocol
11
E-Five Registry
Clinical Outcomes to 12 months per protocol
12
E-Five Registry
Clinical Outcomes to 12 months per protocol
13
E-Five Registry
Clinical Outcomes out to 12 months
E-Five (n7832)
Cardiac Death
MI
TVR
MACE
TLR
TVF
Death
Protocol ST
ARC ST Def/Prob
n191
n135
n128
n82
n88
n349
n387
n565
n587
14
E-Five Registry Safety Analysis
Cumulative Incidence of Cardiac Death and MI to
360 Days
2.9
15
E-Five Registry
Dual Antiplatelet Therapy (DAPT) Usage
16
E-Five Registry Safety Analysis
Cumulative Incidence of Stent Thrombosis
(Protocol) to 360 Days
10
8
6
Cumulative Incidence Thrombosis
4
2
1.0
0
0
90
180
270
360
Time after Initial Procedure (days)
17
E-Five Registry Safety Analysis
Cumulative Incidence of ARC Definite/Probable ST
to 360 Days
10
8
6
Cumulative Incidence Def/Prob Thrombosis
4
2
1.1
0
0
90
180
270
360
Time after Initial Procedure (days)
18
E-FiveMACE and TLR Across Subgroups at 12 Months
MACE
TLR
TLR ()
2.5 mm RVD
Recent MI
Diabetics
Bifurcation
20 mm Lesions
IDDM
All
N3402
N2282
N1694
N2563
N1508
N644
N7832
eFIVE 12 month data Rothamn et al. PCR 2008
19
E-Five Registry
Summary

• The clinical outcomes for patients enrolled
  inthe E-Five Registry were low and
  consistentwith the outcomes seen in the Endeavor
  Clinical Program
• MACE 7.5
• TLR 4.5
• These results were achieved despite almost70 of
  the patients enrolled being considered complex
  including
• 2563 Diabetics
• 1694 Recent Myocardial Infarction patients
• 3402 with lesions 20mm in length
• The 12 month follow up was excellent with 94.2
  (n7832) followed out to 12 months

20
E-Five Registry
Conclusion

• The Endeavor drug eluting stent was associated
  with a consistently low TLR rate regardless of
  lesion complexity
• In this complex patient and lesion cohort the
  cardiac death, MI and ST rates (protocol and ARC
  def/prob) were remarkably low and also consistent
  with the safety findings from the ENDEAVOR
  Clinical Program

21
Back up
22
E-Five Registry
Complex Patients and Lesions
Simple, de novo lesions, within a single vessel,
treated with a single study stent

• Lesions and patients not studied
• in the Endeavor Clinical Program
• Recent MI 21.8
• Multivessel stenting 10.9
• Long lesion (gt26mm) 15.5
• Ostial lesion 4.8
• Bifurcated lesion 16.5
• In-stent restenosis 4.1
• Graft stenting 1.7
• Severe tortuosity 3.0
• Small vessel (RVDlt2.5mm) 9.7
• Large vessel (RVDgt3.5mm) 6.2
• Left main stenting 1.9

Simple
Complex
23
E-Five Registry
Bifurcation Lesions Stent in SidebranchClinical
Outcomes out to 12 months
24
E-Five Registry
Simple Vs Complex Clinical Outcomes out to 12
months
25
E-Five Registry
IDDM NIDDM Clinical Outcomes out to 12 month
26
E-Five Registry
Unstable Angina Clinical Outcomes out to 12 months
27
E-Five Registry
RVD 2.75mm Clinical Outcomes out to 12 months
28
E-Five Registry
Stable vs Unstable Angina Clinical Outcomesout
to 12 months
29
e-Five and ARRIVE I and II Clinical Events to 12
months
E-Five (n7832)
ARRIVE I and II (n7307)
MI (All)
Death
QMI
ARC ST Def/Prob
TLR
Cardiac Death
eFIVE 12 month data Rothman et al. PCR 2008
ARRIVE I and II Taxus IFU 2008
30
e-Five and ARRIVE I and II Clinical Events to 12
months
NA
MI (All)
Death
QMI
ARC ST Def/Prob
TLR
Cardiac Death
eFIVE 12 month data Rothamn et al. PCR 2008
ARRIVE I and II Taxus IFU 2008
31
e-Five and ARRIVE I and II TLR Across Subgroups
at 12 Months
E-Five (n7832)
ARRIVE I and II (n7307)
TLR ()
NA
NA
2.5 mm RVD
MVD
AMI
Bifurcation
Women
20 mm Lesions
Diabetics
IDDM
N1834
N3402
N2282
N1694
N2563
N1508
N854
N644
Endeavor
N2243
N917
N2305
N558
N1148
N746
Taxus
eFIVE 12 month data Rothamn et al. PCR 2008
ARRIVE I and II Taxus IFU 2008
32
e-Five and ARRIVE I and II ST Across Subgroups
at 12 Months
E-Five (n7832)
ARRIVE I and II (n7307)
ARC Def/Prob ()
NA
NA
2.5 mm RVD
MVD
AMI
Bifurcation
Women
20 mm Lesions
Diabetics
IDDM
N1834
N3402
N2282
N1694
N2563
N1508
N854
N644
Endeavor
N2243
N917
N2305
N558
N1148
N746
Taxus
ARRIVE I and II Taxus IFU 2008
eFIVE 12 month data Rothman et al. PCR 2008
33
e-Five and e-Cypher TLR Across Subgroups at 12
Months
E-Five (n7832)
E-CYPHER (n2067)
TLR ()
NA
NA
2.5 mm RVD
MVD
AMI
Bifurcation
Women
20 mm Lesions
Diabetics
IDDM
N1834
N3402
N2282
N1694
N2563
N1508
N854
N644
Endeavor
N124
N155
N640
N260
N318
N200
Cypher
eFIVE 12 month data Rothamn et al. PCR 2008
ARRIVE I and II Taxus IFU 2008
34
e-Five and ARRIVE I and II TLR Across Subgroups
at 12 Months
E-Five (n7832)
ARRIVE I and II (n7307)
TLR ()
NA
NA
2.5 mm RVD
MVD
AMI
Bifurcation
Women
20 mm Lesions
Diabetics
IDDM
N1834
N3402
N2282
N1694
N2563
N1508
N854
N644
Endeavor
N2243
N917
N2305
N558
N1148
N746
Taxus
eFIVE 12 month data Rothamn et al. PCR 2008
ARRIVE I and II Taxus IFU 2008
35
DES Trials Clinical Endpoints to 12 months
TLR
TVR
12-Month Follow-Up
TVF
MACE
ENDEAVOR II
TAXUS IV
SIRIUS
SIRIUS. Holmes et al. Circulation.
2004109634-640.TAXUS IV. Stone et al.
Circulation. 20041091942-1947. Sirius Study 2
year Results Kereiakes. TCTMD Taxus IV 2 Year
Results. Stone TCTMD
36
Taxus IV TLR in Sub Groups to 12 months
37
SIRIUS TLR in Sub Groups to 12 months
38
E-Five Registry
Diabetics Clinical Outcomes to 12 months
39
E-Five Registry
Lesions 20mm Clinical Outcomes to 12 months
40
E-Five Registry
RVD 2.5mm Clinical Outcomes to 12 months
41
E-Five Registry
Multivessel Disease Clinical Outcomes to 12 months
42
E-Five Registry
Recent MI Clinical Outcomes to 12 months
43
E-Five Registry
Bifurcation Lesions Clinical Outcomes to 12 months
44
E-Five Registry
Clinical Outcomes in Women to 12 months
45
E-Five Registry
TLR Across Subgroups at 12 Months
Replace with MACE TLR slide
E-Five (n7832)
TLR ()
2.5 mm RVD
MVD
Recent MI
Diabetics
Bifurcation
Women
All Patients
20 mm Lesions
N3402
N2282
N1694
N2563
N1508
N1834
N7832
N854