1. ENDEAVOR IV: 5 Year Final Outcomes
David E. Kandzari and
Martin B. Leon for the ENDEAVOR IV Trial Investigators

2. ENDEAVOR IV
Study Objectives (2005)
To compare safety and efficacy outcomes measured by target vessel failure (non-inferiority design) among patients randomized to the Endeavor ZES and Taxus PES
To determine whether 8 month angiographic outcomes (in-segment late loss) with the Endeavor ZES are non-inferior to the FDA-approved Taxus PES

3. ENDEAVOR IV
Outstanding Questions (2011)
Does higher late loss with Endeavor ZES stent (compared with Taxus PES) translate into greater late-term TLR beyond the period of angiographic follow-up?
What are the late-term safety outcomes of Endeavor ZES and Taxus PES?
Are Endeavor ZES outcomes consistent with late-term follow up observed in the overall Endeavor Clinical Trial program?

4. Endeavor Global Clinical Program
Enrollment Complete / In Follow Up
1yr 2yr 3yr 4yr 5yr
ENDEAVOR I
Single Arm First-in-Man (n = 100)
5yr
ENDEAVOR II
1:1 RCT vs BMS (E = 598, D = 599) PK (n = 106)
5yr
ENDEAVOR II CA
Continued Access Single Arm (n = 296)
5yr
ENDEAVOR III
3:1 RCT vs Cypher® (E = 323, C = 113)
5yr
ENDEAVOR IV
1:1 RCT vs Taxus® (E = 773, T = 775)
5yr
ENDEAVOR PK
Pharmacokinetic Study (n = 43)
5yr
ENDEAVOR Japan
Single Arm (n = 99)
4yr
E-FIVE
Open Label Single Arm (n = 8300)
2yr
PROTECT
1:1 RCT vs Cypher (E = 4400, C = 4400)
PROTECT CA
Continued Access Single Arm (n ≥ 1000)
EDUCATE
1:1 RCT 12 vs 30 months DAPT (n = 2000–4000)
ENDEAVOR SVS
Small Vessel Single Arm (n ≈ 250)
Enrollment ongoing
E-Japan PMS
Post Mkt Registry Single Arm (n ≈ 2000)

5. ENDEAVOR IV Multicenter Randomized Trial vs Taxus
PI: M. Leon and D. Kandzari
Single De Novo Native Coronary Artery Lesions
Reference Vessel Diameter: 2.5 – 3.5 mm
Lesion Length: ≤ 27 mm
Pre-dilatation required
Endeavor Stent
N = 774
N = 1548 patients
1:1 Randomization
80 US sites
Taxus Stent
N = 774
Clinical endpoints
30d
6mo
8mo
9mo
12mo
2yr
3yr
4yr
5yr
Angio/IVUS endpoints
QCA and IVUS Subset (328 total = 21.2%)
Primary Endpoint: TVF (cardiac death, MI, TVR) at 9mo
Secondary Endpoints: In-segment % DS at 8mo; TLR and TVR at 9mo
Drug Therapy: ASA and clopidogrel/ticlopidine ≥ 6mo

6. ENDEAVOR IV Patient Flowchart Patients Enrolled N = 1548 Endeavor
Taxus
N = 775
Randomized
1:1
Angio F/U (8mo)
144/164
87.8%
Angio F/U (8mo)
135/164
82.3%
Clinical F/U
Clinical F/U
1Yr
761/ %
2Yr 756/ %
3Yr 747/ %
4Yr
732/ %
5Yr
722/ %
1Yr 758/ %
2Yr 754/ %
3Yr 743/ %
4Yr 728/ %
5Yr
718/ %
UC dEN 6

7. ENDEAVOR IV Selected Baseline Characteristics Endeavor n = 773 Taxus
P value
Age (years, mean ± SD)
63.5 ± 11.1
63.6 ± 11.0
0.930
Males (%)
66.9
68.5
0.514
Prior MI (%)
21.1
23.2
0.324
Diabetics (%)
31.2
30.5
0.783
Unstable angina (%)
51.6
49.9
0.567
RVD (mm)
2.73 ± 0.47
2.70 ± 0.46
0.197
Lesion length (mm)
13.41 ± 5.67
13.80 ± 6.09
0.199
B2/C lesions (%)
69.6
70.9
0.578 7

8. ENDEAVOR IV Clinical Outcomes at 5 Years Events % (n) Endeavor n = 722
Taxus
n = 718
P value
Death (all)
10.0 (72)
9.1 (65)
0.59
Cardiac
4.3 (31)
3.8 (27)
0.69
MI (all)
2.6 (19)
6.0 (43)
0.002
Q Wave
0.6 (4)
0.7 (5)
0.75
Non Q wave
2.1 (15)
5.3 (38)
0.001
Death (cardiac) + MI (all)
6.4 (46)
9.2 (66)
0.049
Stent Thrombosis (def/prob)
1.4 (10)
1.9 (14)
0.42
Early (≤ 30 days)
0.4 (3)
0.1 (1)
0.62
Late ( days)
0.0 (0)
0.12
Very Late ( days)
1.8 (13)
0.012
TLR
7.8 (56)
8.4 (60)
0.70
TVR (non-TL)
6.8 (49)
9.5 (68)
0.07
TVR
12.7 (92)
15.0 (108)
0.22
MACE
17.9 (129)
20.3 (146)
0.25
TVF
17.3 (125)
21.3 (153)
0.06 8

9. Cumulative Incidence for TVF Time After Initial Procedure (Years)
ENDEAVOR IV
Cumulative Incidence of Target Vessel Failure to 5 Years
Endeavor ZES
Log Rank P = 0.061
25%
£ 1 year E-ZES 6.6%
PES 9.8%
>1 year to 5 years
E-ZES 10.6%
PES 11.5%
Taxus PES
21.1%
(153)
20%
17.2%
(125)
15%
Cumulative Incidence for TVF
10%
7.2% 5%
6.6% 0% 9M 1 2 3 4 5
Time After Initial Procedure (Years)
Endeavor
773
769
704
685
642
615
566
Taxus
775
755
695
668
627
587
549
Primary endpoint: TVF at 9-months, Pnon-inferiority < 0.001
UC dEN 9 9

10. Cumulative Incidence for TLR Time After Initial Procedure (Years)
ENDEAVOR IV
Cumulative Incidence of TLR to 5 Years
Endeavor ZES
Log Rank P = 0.70
0.9%
10%
Taxus PES
£ 1 year E-ZES 4.5%
PES 3.3%
>1 year to 5 years
E-ZES 3.2%
PES 5.1%
8.6%
(60) 8%
7.7%
(56) 6%
Cumulative Incidence for TLR 4% 2% 0% 1 2 3 4 5
Time After Initial Procedure (Years)
Endeavor
773
695
661
636
594
Taxus
775
771
665
626
593
UC dEN 10

11. ENDEAVOR IV – 5yr Follow Up
TLR Rate Over Time
Endeavor
Taxus
73% Increase
155% Increase
8.4
7.4
7.8
7.1
6.4
5.8
6.1
4.5
4.5
TLR Rate (%)
3.3 1 2 3 4 5 1 2 3 4 5
Years of Follow-up
Years of Follow-up
Values are the event rates. 11

12. Endeavor Pooled Efficacy Analysis
Cumulative Incidence of TLR to 5 Years
Endeavor ZES
25%
Driver BMS
Log rank P < 0.001
£ 1 year E-ZES 5.4%
>1 year to 5 years
E-ZES 2.6%
20%
BMS 13.2%
BMS 3.8%
16.5%
15%
Cumulative Incidence of TLR
10%
7.4% 5% 0% 1 2 3 4 5
Time After Initial Procedure (Years)
Endeavor
2132
2130
1913
1853
1797
1727
Events n (%)
2 (0.1)
113 (5.4)
129 (6.2)
139 (6.7)
146 (7.1)
151 (7.4)
Driver
596
595
489
474
456
445
1 (0.2)
77 (13.2)
83 (14.2)
86 (14.8)
92 (15.9)
95 (16.5) 12 12 12

13. ENDEAVOR IV Cumulative Incidence of Cardiac Death/MI to 5 Years
Endeavor ZES
Log Rank P = 0.048
10%
Taxus PES
£ 1 year E-ZES 2.1%
PES 3.3%
>1 year to 5 years
E-ZES 4.3%
PES 5.9%
9.1%
(66) 8%
6.4%
(46) 6%
Cumulative Incidence of Cardiac Death/MI (%) 4% 2% 0% 1 2 3 4 5
Time After Initial Procedure (Years)
Endeavor
773
769
725
696
675
634
Taxus
775
758
715
684
651
621
UC dEN 13 13

14. ENDEAVOR IV Cumulative Incidence of MI to 5 Years Log Rank P = 0.002
Endeavor ZES
Log Rank P = 0.002
10%
Taxus PES
£ 1 year E-ZES 1.6%
PES 2.6%
>1 year to 5 years
E-ZES 1.0%
PES 3.4% 8%
6.0%
(43) 6%
Cumulative Incidence of Cardiac Death/MI (%) 4%
2.6%
(19) 2% 0% 1 2 3 4 5
Time After Initial Procedure (Years)
Endeavor
773
769
725
696
675
634
Taxus
775
758
715
684
651
621
UC dEN 14 14 14

15. ENDEAVOR IV – 5yr Follow Up
All Non-Q MIs
CKMB Rises (xULN)
Endeavor DES (n=722)
Taxus DES (n=718)
17/34 (50%) of Taxus Non-Q MIs
with CKMB rises ≥10X ULN
Number Patients
≥5X<8X
≥8X<10X
≥10X

16. Time After Initial Procedure (Years)
ENDEAVOR IV
Dual Antiplatelet Therapy Adherence to 5 Years
Endeavor ZES
92.1%
91.4%
Taxus PES
P = 0.02
71.3%
57.6%
54.5%
P = 0.03
65.4%
52.1%
49.0%
47.9%
Adherence to DAPT
54.5%
57.2%
48.2%
45.8%
41.8%
Time After Initial Procedure (Years)
DAPT protocol ≥ 6 months
Physicians and patients unblinded at 12 months
UC dEN 16 16 16

17. ENDEAVOR IV Cumulative Incidence of ARC ST Def/Prob to 5 Years
Endeavor ZES
Log Rank P = 0.42 5%
£ 1 year E-ZES 1.0%
PES 0.1%
>1 year to 5 years
E-ZES 0.4%
PES 1.8%
Taxus PES 4% 3%
Cumulative Incidence for ARC Definite/Probable Stent Thrombosis
2.0%
(14) 2%
1.3%
(10) 1% 0% 1 2 3 4 5
Time After Initial Procedure (Years)
Endeavor
773
731
704
683
642
Taxus
775
774
733
706
674
643
UC dEN 17 17

18. ENDEAVOR IV Cumulative Incidence of Very Late ST to 5 Years5%
Endeavor ZES
Log Rank P = 0.012
Taxus PES 4% 3%
Cumulative Incidence of ARC Def/Prob
Very Late Stent Thrombosis (%) 2%
1.8%
(13) 1%
0.4%
(3) 0% 1 2 3 4 5
Time After Initial Procedure (Years)
Endeavor
737
710
689
648
Taxus
734
707
675
644
UC dEN 18 18

19. ENDEAVOR IV TLR, Cardiac Death/MI and MACE at 1 and 5 Years TLR
Δ 10.5% vs. 13.4%
Δ 3.3% vs. 5.1%
Δ 4.3% vs. 5.9%
1 Year
5 Years

20. ENDEAVOR IV Conclusions at 5 Years
In a trial designed to compare a clinical composite endpoint, a trend toward lower target vessel failure was observed with Endeavor ZES compared with Taxus PES at 5 years
Despite initially higher angiographic late loss with Endeavor ZES,
Rates of TLR beyond period of protocol-mandated angiographic surveillance remain stable with Endeavor ZES
Absolute differences between DES in clinical restenosis temporally decrease, resulting in crossover of event curves favoring Endeavor ZES at 5 years
Recognizing limitations in sample size, late term (5y) follow up of the Endeavor stent demonstrates
Durability in efficacy (TLR)
Compared with Taxus PES, significantly lower rate of VLST with Endeavor ZES
Compared with Taxus PES, emerging differences in MI and cardiac death/MI achieving statistical significance
Late term EIV outcomes with the Endeavor ZES parallel the consistent safety and efficacy observed across the Endeavor Clinical Trials Program