Cypher Endeavor Stent

CYPHER STENT
Interventional Conference
How does it work?
Pathway
Stent Design
Drug Diffusion
SIRIUS
 Higher rate of incomplete stent
apposition (18% vs 9%), but no
clinical events
 No difference in stent thrombosis
(0.8% in both group)
5 yr followup
Pooled Analysis of 5-Year
Follow-Up From 4
Randomized, Controlled
CYPHER vs. Bare-Metal
®
Stent Trials
The CYPHER® Stent Trials: Methodology
 Patient-level
databases of pivotal RCTs were
obtained from Cordis Corporation by the
Cardiovascular Research Foundation with
permission for unrestricted analyses
 RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS
 5-year data available for all trials
 AnalysisPlan (performed by M. Fahy, Sr.
Biostatistician)
 Endpoints
 Safety:

Death (overall, cardiac, non-cardiac); MI (all, QWMI);
Kirtane A.J., et al., TCT 2007; Oral Presentation.
Death through 5 years:
Pooled Analysis of 4 SES vs. BMS RCT’s*
20%
CYPHER Stent (n=878)
Bare Metal Stent (n=870)
15%
HR 1.10 [0.79,1.52]
p=0.57
10% 8.9% (76)
8.2% (69)
5%
0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 870 857 843 824 795 694
CYPHER 878 863 842 817 792 703
* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

Cardiac Death through 5 years:
20%
15%
HR 1.16 [0.72,1.85]
p=0.55
10%
5% 4.4% (37)
3.9% (32)
0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 870 857 843 824 795 694
CYPHER 878 863 842 817 792 703

Myocardial Infarction (MI) through 5 years:
20%
15%
HR 1.15 [0.81,1.63]
p=0.44
10%
7.9% (67)
6.8% (58)
5%
0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 868 824 806 782 751 652
CYPHER 873 832 807 779 751 660

Q-wave MI through 5 years:
20%
15%
HR 1.54 [0.77,3.09]
p=0.22
10%
5%
2.4% (20)
1.6% (13)
0%
0 365 730 1095 1460 1825
Number at risk Days

BMS 869 852 837 816 786 685
CYPHER 877 854 832 804 780 693

Death or MI through 5 years:
20%
Bare Metal Stent (n=870) 15.1% (130)
15%
13.6% (115)
HR 1.12 [0.88,1.45]
p=0.36
10%
5%
0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 868 824 806 782 751 652
CYPHER 873 832 807 779 751 660

Cardiac Death or MI through 5 years:
20%
15%
HR 1.13 [0.84,1.51] 11.1% (94)

10% p=0.43 9.8% (83)
5%
0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 868 824 806 782 751 652
CYPHER 873 832 807 779 751 660

Protocol-defined ST through 5 years:
3.0% Protocol ST Definitions do not count ST after intervening TLR
2.5% CYPHER Stent (n=878)

2.0%
HR 2.19 [0.76,6.32]
1.5% p=0.13
1.3% (11)
1.0%
0.5% 0.6% (5)

After 1 year
6 vs. 0, p=0.02
0.0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 870 853 839 820 791 690
CYPHER 878 858 836 811 785 697

ARC Definite ST through 5 years:
3.0%

2.0%
HR 1.62 [0.67,3.91]
1.5% p=0.28 1.6% (13)
1.0% 1.0% (8)

0.5% After 1 year
9 vs. 4, p=0.19
0.0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 870 853 838 818 789 688
CYPHER 878 859 837 811 784 695

ARC Definite/Probable ST through 5 years:

2.5% HR 0.99 [0.51,1.95]
p=0.99 2.1% (17)
2.0%
2.0% (17)
1.5%
1.0%
0.5% After 1 year

11 vs. 6, p=0.23
0.0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 870 848 834 813 784 683
CYPHER 878 858 835 809 783 694

TLR through 5 years:
30% CYPHER Stent (n=878)

25% 23.9% (205)
20%
HR 0.35 [0.27,0.45]
15% p<0.0001
10% 9.6% (80)
5%
0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 870 680 659 632 603 518
CYPHER 877 827 797 766 732 645

TVR through 5 years:
30% 29.4% (250)
25%
20% CYPHER Stent (n=878)

15% 15.2% (127)
10%
5% HR 0.44 [0.36,0.55]
p<0.0001
0%
0 365 730 1095 1460 1825
Number at risk Days
BMS 869 660 635 603 569 479
CYPHER 876 812 779 737 697 603

On-Label CYPHER® Stent Trials:
Conclusions through 5-year Follow-up
 From this independent, patient-level meta-

analysis from the 4 principal CYPHER® Stent
trials it may be concluded that at 5-year
follow-up of patients with single de novo
native coronary lesions 2.5 – 3.5 mm in
diameter and ≤30 mm in length, polymer-
based sirolimus-eluting stents compared to
otherwise equivalent bare metal stents
result in:
 No significant increase in stent thrombosis
 Nosignificant increase in late stent thrombosis
by ARC definitions Kirtane A.J., et al., TCT 2007; Oral Presentation.
SES in AMI
 TYPHOON STUDY
SES in DM
SES in small Vessel
MVD
 Cypher vs Taxus
All type: SES vs PES
all comers
All type: SES vs PES
all comers
SES vs PES
DM patients
SES vs PES
In-stent restenosis
SES vs PES
long lesions
Meta-analysis: SES vs PES
16 trials
 Couple of precautions
Plavix?: follow up after 6 month of plavix
JACC-Meta Analysis for ST
’06
9-12 month follow-up
 DES vs BMS : MORTALITY/MI
benefit?????
Comprehensive Meta-Analysis
of DES vs. BMS Randomized
Trials and Registries
Ajay J. Kirtane, M.D., S.M.
Gregg W. Stone, M.D.
All-Cause Mortality: All RCTs
8,867 patients, 21 trials %
Weight
Study ID ES (95%
Estimate CI) CI) Weight
(95% (I-V) (%)
SCORPIUS 1.28 (0.35, 4.61) 1.86

SESAMI 0.43 (0.11, 1.63) 1.70
Typhoon 1.01 (0.38, 2.65) 3.27
Passion 0.70 (0.36, 1.36) 6.99
BASKET (SES only) 0.82 (0.37, 1.84) 4.80
STRATEGY 0.84 (0.36, 1.96) 4.30
SES-SMART 0.21 (0.02, 1.71) 0.62
Seville 1.35 (0.23, 7.78) 1.00
HAAMU-STENT 2.00 (0.63, 6.38) 2.30
MISSION! 0.48 (0.09, 2.59) 1.09
PRISON II 0.50 (0.09, 2.67) 1.07
Pache et al 1.40 (0.45, 4.35) 2.40
Ortolani et al 2.00 (0.19, 21.38) 0.55
DIABETES 1.44 (0.48, 4.33) 2.55
RAVEL 1.75 (0.73, 4.16) 4.08
SIRIUS 1.02 (0.67, 1.54) 17.82
C-SIRIUS 0.68 (0.11, 4.04) 0.95
E-SIRIUS 1.08 (0.25, 2.24) 2.57
TAXUS II 1.61 (0.57, 4.53) 2.87
TAXUS IV 0.89 (0.63, 1.25) 26.29
TAXUS V 0.97 (0.57, 1.65) 10.92
I-V Overall Effects
Random (I-squared = 0.0%, p = 0.918) 0.97 (0.81,
0.97 1.15)
(0.81,1.15) 100.00
D+L Overall
*Fixed Effects (I2=0.0%) 0.97 (0.81, 1.15)
0.97 (0.81,1.15), p=0.72
Favors DES Favors BMS
.1 1 10 Mean f/u 2.9 yrs
Ajay J. Kirtane and Gregg W. Stone, 2008
All-Cause Mortality: RCTs (On-Label) %
4,818 patients, 10 trials Weight

Study ID ES (95% CI) (I-V)
Estimate (95% CI) Weight (%)
SCORPIUS 1.28 (0.35, 4.61) 2.84

Pache et al 1.40 (0.45, 4.35) 3.67
Ortolani et al 2.00 (0.19, 21.38) 0.85
RAVEL 1.75 (0.73, 4.16) 6.23
SIRIUS 1.02 (0.67, 1.54) 27.25
C-SIRIUS 0.68 (0.11, 4.04) 1.45
E-SIRIUS 1.08 (0.25, 2.24) 3.93
TAXUS II 1.61 (0.57, 4.53) 4.39
TAXUS IV 0.89 (0.63, 1.25) 40.20
TAXUS V - Simple 1.09 (0.53, 2.22) 9.20
I-V Overall
Random (I-squared = 0.0%, p = 0.927)
Effects 1.05
1.05 (0.84, 1.30) 100.00
(0.84,1.30)
D+L Overall
*Fixed Effects (I2=0.0%) 1.05 (0.84, 1.30) p=0.69
(0.84,1.30),
.1 1 10 Mean f/u 4.0 yrs

All-Cause Mortality: RCT’s (Off-Label) %
4,049 patients, 12 trials Weight
SESAMI 0.43 (0.11, 1.63) 4.90

Typhoon 1.01 (0.38, 2.65) 9.44
Passion 0.70 (0.36, 1.36) 20.16
BASKET (SES only) 0.82 (0.37, 1.84) 13.84
STRATEGY 0.84 (0.36, 1.96) 12.40
SES-SMART 0.21 (0.02, 1.71) 1.80
Seville 1.35 (0.23, 7.78) 2.87
HAAMU-STENT 2.00 (0.63, 6.38) 6.64
MISSION! 0.48 (0.09, 2.59) 3.16
PRISON II 0.50 (0.09, 2.67) 3.10
DIABETES 1.44 (0.48, 4.33) 7.36
TAXUS V - complex 0.84 (0.38, 1.84) 14.32
I-V OverallEffects
Random (I-squared = 0.0%, p = 0.798) 0.84 (0.62, 1.13) 100.00
0.84 (0.62,1.13)
D+L Overall
*Fixed Effects (I2=0.0%) 0.84 (0.62, 1.13) p=0.24
0.84 (0.62,1.13),
.1 1 10 Mean f/u 1.5 yrs

All-Cause Mortality: All Registries
161,232 patients, 28 registries %
Weight
Study ID ES (95% CI) (D+L)
NHLBI (off label, adjusted) 0.94 (0.64, 1.38) 3.40
NHLBI (on label, adjusted) 1.47 (0.87, 2.48) 2.31
Germany Metabolic Syndrome 1.47 (0.65, 3.35) 1.15
Ontario (matched) 0.71 (0.59, 0.84) 5.98
Mayo FFR Substudy 1.00 (0.21, 4.75) 0.36
Italian Diabetic Multivessel (adjusted) 1.22 (0.36, 4.10) 0.57
McMaster STEMI (adjusted) 0.17 (0.03, 0.97) 0.29
Rotterdam Off-Label 0.98 (0.85, 1.13) 6.44
Washington Hosp Center (matched) 1.16 (0.78, 1.75) 3.21
Asan Korea (adjusted) 0.60 (0.46, 0.79) 4.70
SCAAR (adjusted) 1.03 (0.94, 1.14) 6.98
Wake Forest (adjusted) 0.72 (0.55, 0.95) 4.66
Western Denmark (adjusted) 1.00 (0.86, 1.17) 6.29
NY State (adjusted, unmatched) 0.84 (0.72, 0.97) 6.35
MIDAS (adjusted) 0.66 (0.59, 0.74) 6.80
Massachusetts (matched) 0.79 (0.71, 0.89) 6.80
STENT (adjusted) 0.69 (0.55, 0.87) 5.25
Liverpool (matched) 0.45 (0.24, 0.84) 1.78
GHOST (adjusted) 0.55 (0.36, 0.83) 3.09
DEScover (unadjusted) 0.53 (0.35, 0.80) 3.13
Cedars Acute MI 0.82 (0.37, 1.83) 1.20
REAL (adjusted) 0.83 (0.70, 0.98) 6.10
Melbourne 0.67 (0.23, 1.94) 0.73
Multicenter SVG (adjusted) 1.33 (0.47, 3.76) 0.76
ACUITY (from RCT) 0.63 (0.49, 0.82) 4.87
RESTEM 0.73 (0.51, 1.05) 3.63
ARTS II (from RCT) 0.74 (0.41, 1.35) 1.92
ERACI III (from RCT) 1.18 (0.54, 2.58) 1.25
D+L Overall (I-squared =270.1%, p = 0.000) 0.80 (0.72, 0.88) 100.00
*Random Effects (I =70.1%) 0.80 (0.72,0.88), p<0.001
I-V Overall 0.83 (0.79, 0.86)
Fixed Effects 0.83 (0.79,0.86)
NOTE: Weights are from random effects analysis
.1 1 10 Mean f/u 2.5 yrs
MI: All RCTs
8,850 patients, 20 trials
%
Weight
StudyIDID
Study ES (95% CI) (I-V)
SCORPIUS
SCORPIUS 0.82 (0.23, 2.95) 2.02
SESAMI
SESAMI 1.00 (0.20, 4.88) 1.29
Typhoon
Typhoon 0.80 (0.22, 2.97) 1.94
Passion
Passion 0.83 (0.26, 2.69) 2.40
BASKET(All)
BASKET (All) 1.15 (0.64, 2.08) 9.45
STRATEGY
STRATEGY 0.82 (0.31, 2.40) 3.13
SES-SMART
SES-SMART 0.16 (0.04, 0.67) 1.65
HAAMU-STENT
HAAMU-STENT 0.25 (0.03, 2.19) 0.71
MISSION!
MISSION! 0.62 (0.28, 1.39) 5.11
PRISONII II
PRISON 0.83 (0.26, 2.64) 2.44
Ortolanietetalal
Ortolani 1.50 (0.26, 8.61) 1.07
DIABETES
DIABETES 0.60 (0.20, 1.50) 3.23
SCANDSTENT
SCANDSTENT 0.33 (0.09, 1.18) 1.98
RAVEL
RAVEL 1.24 (0.49, 3.14) 3.80
SIRIUS
SIRIUS 0.96 (0.59, 1.55) 14.07
C-SIRIUS
C-SIRIUS 0.59 (0.14, 2.47) 1.59
E-SIRIUS
E-SIRIUS 1.94 (0.93, 4.02) 6.13
TAXUSII II
TAXUS 0.63 (0.23, 1.72) 3.24
TAXUSIVIV
TAXUS 0.99 (0.66, 1.48) 20.13
TAXUSVV
TAXUS 1.27 (0.79, 2.04) 14.59
I-V OverallEffects
D+L
Random (I-squared = 3.0%, p = 0.420) 0.94 (0.79,
0.94 1.13) 100.00
(0.78,1.13)
D+L
I-V Overall
Overall
*Fixed Effects (I2=3.0%) 0.94 (0.78,
0.94 1.13)
(0.79,1.13), p=0.54

.1.1 11 10
10 Mean f/u 2.9 yrs
MI:4,318
RCTs (On Label)
patients, 9 trials
%
Weight
SCORPIUS 0.82 (0.23, 2.95) 3.33

Ortolani et al 1.50 (0.26, 8.61) 1.77
RAVEL 1.24 (0.49, 3.14) 6.29
SIRIUS 0.96 (0.59, 1.55) 23.26
C-SIRIUS 0.59 (0.14, 2.47) 2.63
E-SIRIUS 1.94 (0.93, 4.02) 10.13
TAXUS II 0.63 (0.23, 1.72) 5.36
TAXUS IV 0.99 (0.66, 1.48) 33.28
TAXUS V - Simple 0.98 (0.52, 1.81) 13.95
I-V OverallEffects
Random (I-squared = 0.0%, p = 0.761) 1.03 (0.81,1.30)
1.03 (0.81, 1.30) 100.00
*Fixed Effects (I2=0.0%)
D+L Overall 1.03 (0.81,1.30),
1.03 (0.81, 1.30) p=0.82
.1 1 10 Mean f/u 4.4 yrs

MI: RCT’s (Off Label) %%
Study
StudyIDID
4,532 patients, 12 trialsESES(95%
(95%
CI)
CI)
Weight
Weight
(I-V)
(I-V)
SESAMI
SESAMI 1.00
1.00
(0.20,
(0.20,
4.88)
4.88)3.30
3.30
Typhoon
Typhoon 0.80
0.80
(0.22,
(0.22,
2.97)
2.97)4.97
4.97
Passion
Passion 0.83
0.83
(0.26,
(0.26,
2.69)
2.69)6.16
6.16
BASKET
BASKET(All)
(All) 1.15
1.15
(0.64,
(0.64,
2.08)
2.08)24.22
24.22
STRATEGY
STRATEGY 0.82
0.82
(0.31,
(0.31,
2.40)
2.40)8.03
8.03
SES-SMART
SES-SMART 0.16
0.16
(0.04,
(0.04,
0.67)
0.67)4.24
4.24
HAAMU-STENT
HAAMU-STENT 0.25
0.25
(0.03,
(0.03,
2.19)
2.19)1.83
1.83
MISSION!
MISSION! 0.62
0.62
(0.28,
(0.28,
1.39)
1.39)13.11
13.11
PRISON
PRISONII II 0.83
0.83
(0.26,
(0.26,
2.64)
2.64)6.26
6.26
DIABETES
DIABETES 0.60
0.60
(0.20,
(0.20,
1.50)
1.50)8.29
8.29
SCANDSTENT
SCANDSTENT 0.33
0.33
(0.09,
(0.09,
1.18)
1.18)5.08
5.08
TAXUS
TAXUSVV
- complex
- complex 1.84
1.84
(0.86,
(0.86,
3.94)
3.94)14.52
14.52
I-VI-V
Overall
Overall
Random (I-squared
(I-squared
Effects ==25.5%,
25.5%,pp
==0.194)
0.194) 0.83
0.83
0.77 (0.62,
(0.62,
1.10)
1.10)100.00
(0.54,1.10) 100.00
D+L
D+LOverall
Overall
*Fixed Effects (I2=25.5%) 0.77
0.77
0.83 (0.54,
(0.54,
1.10)
1.10)
(0.62,1.10), p=0.19
.1.1
.1 111 1010
10 Mean f/u 1.5 yrs
MI: All Registries
129,955 patients, 24 registries %
Weight
Study ID ES (95% CI) (D+L)
NHLBI (off label, adjusted) 0.71 (0.50, 1.00) 5.01
NHLBI (on label, adjusted) 0.71 (0.47, 1.05) 4.21
Germany Metabolic Syndrome 0.23 (0.07, 0.78) 0.70
Ontario (matched) 1.10 (0.91, 1.32) 8.26
Brazil Large Vessels 1.50 (0.25, 8.90) 0.33
Italian Diabetic Multivessel (adjusted) 1.02 (0.46, 2.25) 1.50
SCAAR (adjusted) 1.01 (0.91, 1.11) 10.17
Western Denmark (adjusted) 1.29 (1.06, 1.57) 8.02
Massachusetts (matched) 0.92 (0.83, 1.02) 10.10
STENT (adjusted) 0.69 (0.52, 0.92) 6.10
GHOST (adjusted) 1.12 (0.74, 1.70) 4.03
DEScover (unadjusted) 0.69 (0.40, 1.18) 2.80
Cedars Acute MI 0.25 (0.06, 1.16) 0.48
REAL (adjusted) 0.92 (0.76, 1.11) 8.18
Melbourne 1.00 (0.39, 2.58) 1.10
ACUITY (from RCT) 1.07 (0.91, 1.25) 8.90
RESTEM 0.80 (0.52, 1.23) 3.86
ARTS II (from RCT) 0.53 (0.32, 0.88) 3.09
D+L Overall (I-squared
*Random Effects =(I257.9%, p = 0.000)
=57.9%) 0.89 (0.80,0.98),
0.89 (0.80, 0.98) 100.00
p=0.023
I-V Overall
Fixed Effects 0.96 (0.91, 1.01)
0.96 (0.91,1.01)
*MI is NOTE:
QWMI in Washington
Weights Hospital
are from randomCenter, RESTEM
effects analysis
.1 1 10 Mean f/u 2.5 yrs
TVR: All RCTs %
Study ID
7,291 patients, 16 trials ES (95% CI)
Weight
(D+L)
Estimate (95% CI)
Weight (%)
SESAMI 0.36 (0.17, 0.79) 4.36
Typhoon 0.42 (0.25, 0.69) 7.20
STRATEGY 0.34 (0.16, 0.77) 4.22
HAAMU-STENT 0.33 (0.09, 1.19) 1.91
MISSION! 0.38 (0.17, 0.85) 4.08
PRISON II 0.37 (0.19, 0.69) 5.49
Pache et al 0.38 (0.23, 0.64) 7.14
Ortolani et al 0.58 (0.25, 1.36) 3.78
SCANDSTENT 0.17 (0.09, 0.33) 5.44
RAVEL 0.51 (0.25, 1.04) 4.83
SIRIUS 0.48 (0.37, 0.62) 11.51
C-SIRIUS 0.30 (0.10, 0.93) 2.45
E-SIRIUS 0.35 (0.21, 0.56) 7.45
TAXUS II 0.61 (0.35, 1.08) 6.44
TAXUS IV 0.57 (0.45, 0.72) 11.94
TAXUS V 0.77 (0.60, 0.98) 11.75
D+L OverallEffects
*Random (I-squared = 53.2%, p = 0.006)
(I2=53.2%) 0.45 (0.37,
0.45 0.54) p<0.001
(0.37,0.54), 100.00
Fixed Effects
I-V Overall 0.51 (0.45,
0.51 0.57)
(0.45,0.57)
.1 1 10 Mean f/u 3.2 yrs
%
TVR: RCTs (On Label) Weight
Study ID
4,618 patients, 9 trials ES (95% CI) (D+L)
Pache et al 0.38 (0.23, 0.64) 10.44
Ortolani et al 0.58 (0.25, 1.36) 5.08
RAVEL 0.51 (0.25, 1.04) 6.65
SIRIUS 0.48 (0.37, 0.62) 19.03
C-SIRIUS 0.30 (0.10, 0.93) 3.19
E-SIRIUS 0.35 (0.21, 0.56) 10.98
TAXUS II 0.61 (0.35, 1.08) 9.25
TAXUS IV 0.57 (0.45, 0.72) 19.99
TAXUS V - Simple 0.91 (0.64, 1.29) 15.38
D+L Overall Effects

*Random (I-squared
(I2==48.8%)
48.8%, p = 0.048) 0.53 (0.43,
0.53 0.65)
(0.43,0.65), 100.00
p<0.001
Fixed Effects
I-V Overall 0.54 (0.47,
0.54 0.62)
(0.47,0.62)

.1 1 10 Mean f/u 4.2 yrs

%
TVR: RCTs (Off Label) Weight
Study ID
2,673 patients, 8 trials ES (95% CI) (D+L)
SESAMI 0.36 (0.17, 0.79) 10.65
Typhoon 0.42 (0.25, 0.69) 16.43
STRATEGY 0.34 (0.16, 0.77) 10.35
HAAMU-STENT 0.33 (0.09, 1.19) 4.98
MISSION! 0.38 (0.17, 0.85) 10.04
PRISON II 0.37 (0.19, 0.69) 13.06
SCANDSTENT 0.17 (0.09, 0.33) 12.95
TAXUS V - complex 0.62 (0.44, 0.86) 21.55
D+L Overall Effects

*Random (I-squared(I2==47.8%)
47.8%, p = 0.063) 0.38 (0.27,
0.38 0.52)
(0.27,0.52), 100.00
p<0.001
Fixed Effects
I-V Overall 0.42 (0.34,0.52)
0.42 (0.34, 0.52)

.1 1 10 Mean f/u 1.6 yrs

TVR: All Registries %
Study ID
73,819 patients, 17 registries ES (95% CI)
Weight
(D+L)
Estimate (95% CI)
Weight (%)
Ontario (matched) 0.69 (0.60, 0.80) 9.88
Brazil Large Vessels 0.43 (0.17, 1.10) 1.57
NY State (adjusted, unmatched) 0.54 (0.50, 0.60) 10.70
STENT (adjusted) 0.58 (0.47, 0.71) 8.70
GHOST (adjusted) 0.28 (0.20, 0.39) 6.31
Montevergine 0.51 (0.39, 0.68) 7.30
DEScover (adjusted) 0.58 (0.40, 0.83) 5.81
Cedars Acute MI 0.22 (0.08, 0.62) 1.34
REAL (adjusted) 0.67 (0.59, 0.76) 10.17
Multicenter SVG (adjusted) 0.58 (0.28, 1.18) 2.41
RESTEM 0.62 (0.47, 0.80) 7.53
D+L Overall Effects
*Random (I-squared(I=
2 71.2%, p = 0.000)
=71.2%) 0.53 (0.47,
0.53 0.61)
(0.47,0.61), 100.00
p<0.001
I-V Overall
Fixed Effects 0.57 (0.54,
0.57 0.60)
(0.54,0.60)
Favors DES Favors BMS Mean f/u 2.2 yrs

.1 1 10
Conclusions (1)
In 22 RCTs in which 9,470 pts were randomized to
DES or BMS and followed for ≥1 yr, DES resulted in:
• Non significant 3% and 6% reductions in mortality
and MI respectively
• A highly significant 55% reduction in TVR
In 30 registries in which 174,302 pts were treated
with either DES or BMS and followed for ≥1 yr, DES
resulted in:
• A highly significant 20% reduction in mortality
• A significant 11% reduction in MI
• A highly significant 47% reduction in TVR
Final Note
 Majority of trial at short term
followup.
 No randomized studies so far to look
at mortality benefit/harm between
BMS and DES
 All powered to look at TLR and re-
stenosis preventions.
Final Note
 Of course there is sign benefit for TLR (5-
8% vs 30%)
 This is off set with slight (p= NS) increase
in late ST.
 This has not translated into increase mortality
in meta-analysis and registeries.
 We still do not know optimal time for anti
platelet therapy, but at least 1 yr
recommended.
 Increase risk of ST with increasing length
of stent
Endeavor Stent
Endeavor-Pharmocology
Mechanism
Mechanism
Mechanism
Drug Elution
• Zotarolimus elutes completely from the PC polymer coating

to the injury site by the fourteenth day post-implant
100
Percent Drug Eluted (%)
80
60
40
20
0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14
Days
Preclinical studies on file at Medtronic, Inc.

Strut Comparison
Low-Profile Stent and Polymer
The Endeavor stent has thin struts and a thin
polymer coating compared with other DES
PC basecoat
(~1 μm thick) Post-elution
~1-μm coating
of PC polymer
Drug layer
Stent Stent
90% zotarolimus (10 μg/mm) strut strut Illustrations
10% PC (~2–3 μm thick) not to scale
PC overspray
(~0.1 μm thick)
3.0-mm stents
500x magnification
Endeavor Taxus® Cypher®

Drug/polymer 4 μm (2.7 d/1.4 p) 16 μm 13 μm
Strut thickness 91 μm 132 μm 140 μm
Total thickness 95 μm 148 μm 153 μm
Taxus is a registered trademark of Boston Scientific Corporation. Cypher is a registered trademark of Cordis Corporation
Polymer
 Inert polymer-does not induce
inflammation
 Physiological polymer
Stent Summary
 Drug
 Zotarolimus
 Pharmocokenetic (similar to sirolimus)
 Mechanism (similar to sirolimus)
 Polymer
 PC
 Dilevery system
 Driver Stent
 Significantly smaller profile
Endeavor Clinical Program
Overview
Premarket Safety and Efficacy Package
9m 2yr 3yr
4yr
ENDEAVOR I Single Arm First-in-Man (n=100) 4yr
ENDEAVOR II 1:1 RCT vs. BMS (E=598,D=599) PK (n=106) 3yr
ENDEAVOR II CA Continued Access Single Arm (n=296) 2yr
ENDEAVOR III 3:1 RCT vs. Cypher® (E=323,C=113) 2yr
ENDEAVOR IV 1:1 RCT vs.Taxus® (E=773,T=775) 12mo
ENDEAVOR PK Pharmacokinetic Study (n=43) 9mo
ENDEAVOR Japan Single Arm (n=99) 9mo
Ongoing
1:1 RCT vs. Cypher (E=4400,C=4400)
PROTECT
E-FIVE Open Label Single Arm (n=8000)
Proposed
US Post Approval Open Label Single Arm Study (n=5000)
ST
Endeavor IV
Patient Flowchart
Patients Enrolled
N = 1548
Endeavor Taxus
Randomized
n = 773 n = 775
Angio F/U (8 mo) Angio F/U (8 mo)

144/164 135/164
87.8% 82.3%
Clinical F/U Clinical F/U

(9 mo) (12 mo) (9 mo) (12 mo)
758/773 749/773 749/775 741/775
98.1% 96.9% 96.6% 95.6%
Endeavor IV
Primary Endpoint Result
at 9 months
Target Vessel Failure
P for Non-Inferiority < 0.001
Δ=3.8%
6.6% 7.2%
TVF Rate
Endeavor Taxus
(n=50/758) (n=54/749)
Endeavor IV
8 Month QCA
Endeavor Taxus
P value
(144 pts) (135 pts)
RVD (mm) 2.65 ± 0.47 2.68 ± 0.45 0.635
MLD (mm)
In-stent 1.95 ± 0.61 2.25 ± 0.61 <0.001
In-segment% DS 1.80 ± 0.55 1.98 ± 0.56 0.008
% DS
26.41 ± 16.09 ±
In-stent <0.001
19.74±
32.28 17.99±
26.61
In-segment 0.004
17.02 15.52
Late loss (mm)
In-stent 0.67 ± 0.49 0.42 ± 0.50 <0.001
In-segment 0.36 ± 0.47 0.23 ± 0.45 0.023
Endeavor IV
Clinical Events at 12 months
Endeavor Taxus
P-Value
n=749 n=741
Death (all) – % (#) 1.1(8) 1.1(8) 1.000
Cardiac 0.5 (4) 0.5 (4) 1.000
MI (all) – % (#) 1.6 (12) 2.6 (19) 0.208
Q Wave 0.3 (2) 0.1 (1) 1.000
Non Q wave 1.3 (10) 2.4 (18) 0.131
Death (cardiac) + MI (all) –
2.1 (16) 3.1 (23) 0.260
% (#) (all) – %
Stent Thrombosis
0.8 (6) 0.1 (1) 0.124
(#)
0-30 days 0.4 (3) 0.1 (1) 0.625
31-360days 0.4* (3) 0 0.250
TLR – % (#) 4.5 (34) 3.2 (24) 0.228
TVR (non-TL) – % (#) 2.5 (19) 4.2 (31) 0.085
TVR – % (#) 6.3 (47) 6.7 (50) 0.753
MACE – % (#) 6.5 (49) 6.6 (49) 1.000
TVF – % (#) 7.7 (58) 9.4 (70) 0.267
*Day 83, 145, 171

Endeavor IV
TVF Free Survival to 360
100%
days Endeavor Taxus P (log rank)
TVF-free 92.3% 90.6% 0.243
Freedom from TVF
95%
90%
Endeavor Taxus
85%
0 30 60 90 120 150 180 210 240 270 300 330 360
Time after Initial Procedure (days)
TVF 0 30 18 27 36
Endeav 773 760 0
737 0
712 0
670
or
Taxus 775 748 721 692 655
Endeavor IV
Target Vessel
Revascularization
9 months 12 months
P = 0.753
P = 0.728
6.3% 6.7%
5.4% 4.9%
Rate
Endeavor Taxus Endeavor Taxus

(41/758) (37/749) (47/749) (50/741)
Endeavor IV
Target Lesion
Revascularization
9 months 12 months
P = 0.228
P = 0.154
Rate
4.1% 4.5%
2.7% 3.2%

(31/758) (20/749) (34/749) (24/741)
Endeavor IV
TLR by Angiographic Follow-up
at 12 months
P =0.070
8.5%
P =0.875
TLR Rate
3.6% 3.3%
3.0%
12/141 4/133 22/608 20/608

Angiographic Follow-up Clinical Follow-up
Endeavor IV
TVF – Post Hoc Subgroup Analysis
Risk Ratio P-Value
Risk Ratio Endeavor Taxus
[95% CI] Interaction
Diabetes 0.76 7.9% 8.5%

0.960
Non-diabetes 1.10 6.2% 6.9%
RVD
≤2.5mm 0.82 7.3% 9.0%
>2.5 <3.0mm 1.13 7.2% 6.4% 0.479
≥3.0mm 0.81 5.5% 6.7%
Lesion Length
≤ 10mm 0.65 4.4% 6.8%
>10 <20mm 1.19 8.0% 6.7% 0.735
≥ 20mm 0.53 5.8% 11.0%
Single Stent 1.01 6.2% 6.2%

0.901
Multiple Stents 0.95 14.3% 15.1%
0.1 Favors 1 Favors 10
Endeavor Taxus
Endeavor Conclusion
 More flexible, smaller struts (driver
stent)
 Similar pharmo-kenetics to Cypher
 Non inferior to Cypher and Taxus for
MACE
 But higher late loss/re-stenosis
 Possibly no last stent thrombosis????

Cypher Endeavor Stent

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Cypher Endeavor Stent

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CYPHER STENT

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

Number at risk Days

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

HR 1.13 [0.84,1.51] 11.1% (94)

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

3.0% Protocol ST Definitions do not count ST after intervening TLR

2.5% CYPHER Stent (n=878)

0.5% 0.6% (5)

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

2.5% CYPHER Stent (n=878)

1.0% 1.0% (8)

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

3.0% CYPHER Stent (n=878)

0.5% After 1 year

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

30% CYPHER Stent (n=878)

10% 9.6% (80)

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

30% 29.4% (250)

20% CYPHER Stent (n=878)

* RAVEL, SIRIUS, E-SIRIUS, C-SIRIUS

 From this independent, patient-level meta-

SCORPIUS 1.28 (0.35, 4.61) 1.86

4,818 patients, 10 trials Weight

SCORPIUS 1.28 (0.35, 4.61) 2.84

Favors DES Favors BMS

.1 1 10 Mean f/u 4.0 yrs

Ajay J. Kirtane and Gregg W. Stone, 2008

SESAMI 0.43 (0.11, 1.63) 4.90

Favors DES Favors BMS

.1 1 10 Mean f/u 1.5 yrs

Favors DES Favors BMS

SCORPIUS 0.82 (0.23, 2.95) 3.33

Favors DES Favors BMS

.1 1 10 Mean f/u 4.4 yrs

Ajay J. Kirtane and Gregg W. Stone, 2008

Favors DES Favors BMS

Estimate (95% CI) Weight (%)

Pache et al 0.38 (0.23, 0.64) 10.44

Ortolani et al 0.58 (0.25, 1.36) 5.08

RAVEL 0.51 (0.25, 1.04) 6.65

SIRIUS 0.48 (0.37, 0.62) 19.03

C-SIRIUS 0.30 (0.10, 0.93) 3.19

E-SIRIUS 0.35 (0.21, 0.56) 10.98

TAXUS II 0.61 (0.35, 1.08) 9.25

TAXUS IV 0.57 (0.45, 0.72) 19.99

TAXUS V - Simple 0.91 (0.64, 1.29) 15.38

D+L Overall Effects

NOTE: Weights are from random effects analysis

Ajay J. Kirtane and Gregg W. Stone, 2008

TVR: RCTs (Off Label) Weight

Estimate (95% CI) Weight (%)

SESAMI 0.36 (0.17, 0.79) 10.65

Typhoon 0.42 (0.25, 0.69) 16.43

STRATEGY 0.34 (0.16, 0.77) 10.35

HAAMU-STENT 0.33 (0.09, 1.19) 4.98

MISSION! 0.38 (0.17, 0.85) 10.04

PRISON II 0.37 (0.19, 0.69) 13.06

SCANDSTENT 0.17 (0.09, 0.33) 12.95