1. Long Term Clinical Results from the Endeavor Program: 5-Year Follow up
David E. Kandzari, Martin B. Leon, William Wijns, Ian T. Meredith, Jean Fajadet, Donald E. Cutlip, Laura Mauri,
on Behalf of the Endeavor Program Investigators

2. Endeavor Late-Term Clinical Outcomes
Background
Emphasis on DES-related outcomes has shifted temporally from early to late occurring events
Shorter term (<1 year) angiographic and revascularization outcomes for DES trials have served as a benchmark for DES efficacy
Recent evaluations have identified emerging disparities in outcomes between DES, highlighted in late-term follow up
Pooled analyses of alternative DES demonstrate continuation of events beyond the primary endpoint
Late-term efficacy outcomes with the Endeavor ZES were examined to assess durability and relative differences to BMS

3. Endeavor Pooled Analysis
ENDEAVOR I
First in Human 60 months n = 97/100 (97%)
ENDEAVOR II
Double-blind Randomized Trial 60 months n = 577/598 (96%)
ENDEAVOR II CA Registry
Continued Access Registry 60 months n = 287/296 (97%)
ENDEAVOR III
Confirmatory Trial vs. Cypher 60 months n = 307/323 (95%)
ENDEAVOR IV
Confirmatory Trial vs. Taxus 36 months n = 734/773 (95%)
ENDEAVOR PK
Pharmacokinetic Trial 36 months n = 42/43 (98%)
720 days follow up
N = 2088
1080 days follow up
N = 2063
1440 day follow up
N = 1278
1800 day follow up
N = 1268

4. Endeavor Pooled Analysis
Baseline Characteristics
Endeavor (n = 2132)
Driver (n = 596)
P Value
Age – years (mean ±SD)
62.5 ± 10.7
61.9 ± 10.5
0.230
Males (%)
71.5
75.3
0.060
Diabetics (%)
26.1
22.2
0.054
Unstable Angina (%)
40.8
33.3
0.002
RVD (mm)
2.73
2.76
0.128
Lesion length (mm)
14.16
14.38
0.446
B2/C lesions (%)
71.4
79.0
<0.001

5. Endeavor Safety Analysis
Dual Antiplatelet Therapy (DAPT)
Patients On DAPT At:
1 Year
2 Years
3 Years
4 Years
5 Years
ENDEAVOR (Pooled)
38.8 (790/2036)
31.0
(617/1990)
23.7 (457/1931)
7.9 (95/1197)
7.5
(88/1173)
Driver
29.0
(166/572)
13.5 (76/562)
9.1
(50/548)
9.2
(50/546)
8.6
(46/534)
Data presented as percentages.

6. Endeavor Safety Analysis
Cumulative Incidence of ARC Def/Prob Stent Thrombosis to 5 Years 5%
Driver
Endeavor
£ 1 year Endeavor ST = 0.62%
> 1 year Endeavor ST = 0.18%
Log rank P = 0.051 4% 3%
Cumulative Incidence of
Def/Prob Thrombosis 2%
1.7% 1%
0.8% 0%
360
720
1080
1440
1800
Time after Initial Procedure (days)
Days
360
720
1080
1440
1800
Endeavor
2132
2131
2044
1989
1687
1199
Events n (%)
1 (0.1)
13 (0.6)
15 (0.7)
16 (0.8)
Driver
596
595
570
559
543
538
1 (0.2)
8 (1.4)
9 (1.5)
10 (1.7)
By intention to treat (ITT), 2 Endeavor patients had ST at day 354 and day 1349; and 1 Driver patient had an ST at day 842, secondary to TLR. Per the ARC definition, these uncensored events are included in the primary ITT analysis despite the fact that the events may not be related to the study devices.

7. Endeavor Safety Analysis
Cumulative Incidence of Cardiac Death and MI to 5 Years
15%
£ 1 year Endeavor Cardiac Death
MI = 2.8%
> 1 year Endeavor Cardiac Death
MI = 2.4%
Endeavor
Log rank P = 0.003
Driver
10%
8.4%
Cumulative Incidence of Cardiac Death or MI
5.2% 5% 0%
360
720
1080
1440
1800
Time after Initial Procedure (days)
Days
360
720
1080
1440
1800
Endeavor
2132
2102
2009
1951
1649
1168
Events n (%)
30 (1.4)
60 (2.8)
72 (3.4)
79 (3.8)
87 (4.4)
96 (5.2)
Driver
596
581
555
544
529
523
15 (2.5)
27 (4.5)
34 (5.8)
39 (6.6)
41 (7.0)
49 (8.4)

8. Endeavor Efficacy Analysis
Cumulative Incidence of TLR to 5 Years
25%
Driver
Endeavor
£ 1 year Endeavor TLR = 5.4%
> 1 year Endeavor TLR = 1.6%
Log rank P < 0.001
20%
16.5%
15%
Cumulative Incidence of TLR
10%
7.0% 5% 0%
360
720
1080
1440
1800
Time after Initial Procedure (days)
Days
360
720
1080
1440
1800
Endeavor
2132
2130
1908
1842
1552
1100
Events n (%)
2 (0.1)
113 (5.4)
129 (6.2)
139 (6.8)
140 (6.8)
142 (7.0)
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)

9. Endeavor: Long Term Efficacy
Predictors of TLR at 1 Year vs >1 Year
To 1 year
Odds Ratio
P Value
History of Hypertension
1.601
0.074
B2/C Lesions
1.566
0.082
Angiographic follow up
2.156
<0.001
From 1 to 3 years
Odds Ratio
P Value
History of Hypertension
2.847
0.050
<1 yr: Multiple logistic regression returned 3 predictors, QCA, Hypertension and B2/C lesions; current analysis only shows QCA significant, in previous version (PCR), all three were significant.
>1 yr: Multiple logistic regression returned the Hypertension as predictor only – previous version also showed RVD as predictor but this value is now no longer showing in multiple regression model.
The variables in the footnote went into the simple logistic regression
Variables used in the model include: RVD (per mm), HTN, prior MI, LAD (vs non-LAD), DM, B2/C vs. A/B1, prior PCI, unstable angina, lesion length (per mm), male vs. female, hyperlipidemia, AMI, prior CABG, age (years), angiographic follow up

10. Endeavor: Long Term Efficacy
Sub Groups: Early and Late TLR Rates
TLR Rates
All
NIDDM
IDDM
RVD <2.75
Lesion ≥20 mm
Angio
Non- Angio

11. Endeavor: Long Term Clinical Outcomes
Conclusions
Against the background of an excellent safety profile:
Treatment with the Endeavor ZES is associated with a stable and durable rate of TLR through 5-year follow up
The stability in annualized rates of TLR is consistent across the individual trials and is distinguished from BMS
Favorable efficacy outcomes are consistent across subgroups at highest risk for clinical restenosis
In the context of clinical trials, predictors of late TLR are distinct from those associated with early (<1 year) events
These findings underscore the importance of shifting focus to include late term clinically relevant outcomes for a more complete perspective of DES safety and efficacy