Bare Metal Stents: Will Their Lower Thrombosis Advantage over DES Vanish Against the CoCr-Everolimus Eluting Stents? Armando Tellez, SOLACI Congress 2012, Mexico.

1. Bare Metal Stents: Will Their Lower
Thrombosis Advantage over DES Vanish
Against the CoCr-Everolimus Eluting
Armando Tellez, MD
Skirball Center for Cardiovascular Research
Cardiovascular Research Foundation
New York, NY

2. Disclosures
• I, Armando Tellez, DO NOT have a financial
interest/arrangement or affiliation with one or
more organizations that could be perceived as a
real or apparent conflict of interest in the context
of the subject of this presentation

3. 1st Gen Drug-Eluting Stents
Late loss = 0
Great Success at follow up after 1st Generation DES
implantation
NO RESTNOSIS
7 years

4. 1st Gen Drug-Eluting Stents
Late loss = 0
Great Success at follow up after 1st Generation DES
implantation
NO RESTNOSIS = Delayed Vascular Healing
7 years
Giant cells BMS DES
Eos
Inflammation Fibrin Persistance Incomplete Endothelialization
Toxi c positive remodeling/
Polymer Malapposition

5. 1st Gen Drug-Eluting Stents
Late loss = 0
Great Success at follow up after 1st Generation DES
implantation
Late stent
NO RESTNOSIS = Delayed Vascular Healing
thrombosis
7 years
Giant cells BMS DES
Eos
Inflammation Fibrin Persistance Incomplete Endothelialization
Toxi c positive remodeling/
Polymer Malapposition

6. 1st Gen Drug-Eluting Stents
Late loss = 0
Great Success at follow up after 1st Generation DES
implantation
Late stent
NO RESTNOSIS = Delayed Vascular Healing
thrombosis
7 years
Giant cells BMS DES
Eos
Inflammation Fibrin Persistance Incomplete Endothelialization
Toxi c positive remodeling/
Polymer Malapposition

7. 1st Gen Drug-Eluting Stents
PES (N=93 BMS (N=32
Lesions, 34 142 Lesions, 9997 P
Struts) Struts)
Strut-level analysis
Struts analyzed 384±297 322±213 0.51
Total Covered Struts 32 257 9878
% Covered Struts 94.3±7.0 98.9±2.5 <0.0001
Embedded 88.1±12.3 98.0±4.3 <0.0001
Protruding 6.3±8.0 1.0±2.1 <0.0001
Total Uncovered Struts 1885 119
% Uncovered Struts 5.7±7.0 1.1±2.5 <0.0001
Apposed 4.8±5.3 1.0±2.3 <0.0001
Malapposed 0.9±2.1 0.1±0.2 0.0003
Neointimal thickness 0.17±0.12 0.34±0.17 <0.0001
Guagliumi G et al. Circulation 2011;123:274-281

8. ARC-ST (Definite/Probable) at 5 Years
TAXUS I, II-SR, IV & V (n=2,797)
5%
TAXUS (n=1400)
BMS (n=1397) 5-Year HR [95% CI]:
Stent thrombosis (%)
4%
1.37 [0.79, 2.38]
2.3%
P=0.26 (n=30)
3%
2%
1% 1.7%
(n=22)
0%
0 1 2 3 4 5
Years
Event Rate ± 1.5 SE Stone GW et al. JACC CV Int 2011;4:530–42

9. Myocardial Infarction at 5 Years
TAXUS I, II-SR, IV & V (n=2,797)
15%
TAXUS (n=1400)
Myocardial infarction (%)
BMS (n=1397)
5-Year HR [95% CI]:
1.15 [0.87, 1.53] 7.7%
10% (n=102)
P=0.33
5%
6.6%
(n=89)
0%
0 1 2 3 4 5
Years
Event Rate ± 1.5 SE Stone GW et al. JACC CV Int 2011;4:530–42

10. Myocardial Infarction: Landmark
Analysis TAXUS I, II-SR, IV & V (n=2,797)
10%
TAXUS (n=1400)
Myocardial infarction (%)
BMS (n=1397)
1-5 Year HR [95% CI]:
1.67 [1.06, 2.65]
4.5%
P=0.03
5% 0-1 Year HR [95% CI]: 3.8%
0.89 [0.62, 1.27]
P=0.52
4.0%
2.3%
0%
0 1 2 3 4 5
Years
Event Rate ± 1.5 SE Stone GW et al. JACC CV Int 2011;4:530–42

11. SYNTAX: ARC Stent Thrombosis
Definite ARC ST (Per Patient) Probable ARC ST (Per Patient)
8.8
~4.5% ST ~1.3% ST/yr
in year 1 in years 2-4
Patients, %
2.6
1.7 1.4
1.3 1.1
0.3
Acute Subacute Late Very Late Total
≤1d 2-30d 31-365d 366-730d 731-1095d 1096-1460d 4 year
Days Postprocedure
1 patient had an ST 1d and 6d post-procedure; therefore, counted in the ≤1d and 2-30d intervals but only once in the total.
Serruys PW. TCT 2011
SYNTAX 4-year Outcomes • EACTS 2011 • Serruys • October 2011 • Slide 11

12. HORIZONS-AMI: Stent Thrombosis
(ARC Definite or Probable)
6
TAXUS DES (n=2238)
Stent Thrombosis (%) EXPRESS BMS (n=744)
5
4.8%
4
4.3%
3.4%
3 3-yr HR [95%CI]=
3.1%
1.10 [0.74, 1.65]
2 P=0.63
1-yr HR [95%CI]=
1 0.92 [0.58, 1.45]
P=0.72
0
0 3 6 9 12 15 18 21 24 27 30 33 36
Months
Number at risk
TAXUS DES 2238 2108 2066 2013 1980 1932 1341
EXPRESS BMS 744 695 683 664 654 637 425
Stone GW et al. Lancet 2011;377:2193-204

13. 100 100
Y=17.8x + 30.4 Y=16.5x + 31.3
r= 0.73 r= 0.66
Neointima% Stenosis
Neointima% Stenosis
80 P <0.01 80 P <0.01
n=21 n=21
60 60
40 40
20 20
0 0
0 1 2 3 0 1 2 3
Injury Score Inflammatory Score
Score 0 Score 1 Score 2 Score 3
J Am Coll Cardiol. 1998 Jan;31(1):224-30

14. Impact of Strut Thickness on Vascular Healing
and Neointimal Formation in BMS
Rabbit Model: 7-Days Thin= 82 um
Thick= 162 um
Thick
Thin
28-Days
(%)
Thick Thick
40 3
Strut Coverage Thin
(%) Thin
Score
60
30
2
P= 0.008 20
40
20
1
10
0 0 0
Thick Thin
Fibrin Score Inflammation Score
% Stenosis
Presented by Renu Virmani

15. Strut Thickness Effect on Restenosis
Outcome (ISAR-STEREO-2) Trial
Deep Wall Trauma Reduction
Thin-Strut Thick-Strut
p Value
(n = 309) (n = 302)
B2/C Lesions 255 (82) 213 (70) < 0.001
Chronic Occlusions, n (%) 15 (5) 26 (9) 0.06
Restenotic Lesions, n (%) 10 (3) 13 (4) 0.49
Lesion Length, mm 13.9 ± 7.8 14.1 ± 7.8 0.77
Vessel Size, mm 2.93 ± 0.50 2.91 ± 0.51 0.68
Diameter Stenosis, % 68.2 ± 18.9 70.8 ± 20.4 0.11
p <0.001
p <0.001 p Value
Thin-Strut Thick-Strut
(n = 229) (n = 236)
MLD, mm 1.96 ± 0.76 1.70 ± 0.83 < 0.001
DS, % 33.4 ± 21.5 42.4 ± 24.1 < 0.001
LL, mm 0.93 ± 0.61 1.19 ± 0.69 < 0.001
LL index 0.51 ± 0.37 0.65 ± 0.44 < 0.001
Restenosis, n (%) 41 (17.9) 74 (31.4) < 0.001
Pache J. JACC. 2003 Apr 16;41(8):1283-8

16. Impact of Strut Thickness on Vascular Healing and
Neointimal Formation in BMS
Strut Coverage at 14 days in Rabbit
P=0.05
%
P=0.001
100
94.83
80
88
77
60
40
20
0
Express Liberté Element
Express Liberté Element
132 μm 97 μm 81 μm
Soucy N, Feygin J et al, EuroIntervention 2011

17. Progression in Stent Platform Design
Strut Thickness and Biomaterials
1st 2nd 3rd 4th 1st Gen
Generation Generation Generation Generation BVS
Stainless Steel Cobalt Alloys Platinum Chromium PLLA
0.140 mm 0.132 mm 0.096 mm 0 .081 mm 0.091 mm 0.081 mm 0.081 mm 0.074 mm 0.150 mm
(0.0055” ) (0.0052”) (0.0038”) (0.0032” ) (0.0036”) (0.0032”) (0.0032”) (0.0029”) (0.0059”)
TAXUS® TAXUS® Xience V® Endeavor® Xience SYNERGY™ BVS
Cypher®
Express® Liberté® Stent Stent Prime® Stent
Stent
Stent Stent Stent

18. SPIRIT II, III, IV and COMPARE trials
Pooled database analysis (n=6,789)
Stent thrombosis (ARC definite/probable)
3
EES (n=4,247) HR: 0.30 [0.19, 0.47]
PES (n=2,542) p<0.001
ARC def or prob (%)
Stent thrombosis
2.3%
2
1
0.7%
0
0 3 6 9 12 15 18 21 24
Time in Months
Number at risk
XIENCE 4247 4177 4082 3998 3479
TAXUS 2542 2463 2408 2350 2110
Kereiakes DJ et al. EuroIntervention 2011:7:74-83

19. SPIRIT II, III, IV and COMPARE trials
Pooled database analysis (n=6,789)
Stent thrombosis (ARC def/prob) at 2 years
0.25 (0.12–0.52)
0.34 (0.19–0.62) P=0.0002
P=0.0002
Planer D et al. JACC Cardiovasc Interv. 2011;4:1104-15

20. 14 Day Endothelialization: Rabbit Iliac Model
XIENCE V CYPHER TAXUS ENDEAVOR
Joner M et al. JACC 2008;52:333-42

21. Functional Endothelial Re-growth
Rabbit Iliac, CD-31 Staining, 14-day
CD-31 = PECAM (Platelet Endothelial Cell Adhesion Molecule), which
mediates adhesion to endothelial cells and function in immunity,
inflammation and wound healing. The presence of CD-31 is an indicator
of endothelial healing and normal endothelial function.
XIENCE™ V CYPHER® TAXUS® ENDEAVOR™
Over Struts
Between Struts
CD31: Green Channel
Joner M et al. JACC 2008;52:333-42

22. The Concept of Fluoropassivation
Fluoropolymer coated surfaces are
thromboresistant in blood-contact application
20
3000
Thrombus Formation (%)
18 30 min
60 min
16 120 min 2500
Platelets / mm2
14
2000
12
10 1500
8
6 1000
4
500
2
0 0
PAN PAN91 PAN82 PAN73 PVDF BASE PP0212L PTM0212F PTM0212I
Comparison of thrombus formation ratio of Platelet adhesion onto different polymeric surfaces
PAN/PVDF blend membranes after 30, 60 and after 15 min exposure to blood at 150 rpm (37° C).
120 min incubation (n=3). Platelet count measured using 51Cr method.
Ting-Yu Liu et al. Polym. Adv. Technol. Massa TM et al. J Biomed Materials Research
2005;16:413–419 Part A DOI 10.1002/jbm.a

23. Biocompatibility
XIENCE V – Thromboresistant
Chandler Blood Loop Test (2 h Exposure)
p = 0.0001
Weight of Thrombus (µg) Adhered on Stent
4000
3138
3500
3000
p = 0.003
2500
2000
p = 0.02
1500
752 871
1000
211
500
0
XIENCE V (n = 10) Endeavor (n = 8) Cypher (n = 8) Taxus Liberte (n = 8)
Data on file at Abbott Vascular

24. Hemocompatible Polymer
Unheparinized Ex-Vivo Shunt Study
0.25 200
Avg. Weight Increase (g)
0.20
Blood Flow (mL/min)
150 XIENCE V
n=9
0.15
100
0.10
50
0.05
VISION
n=8
0.00 0
XIENCE V VISION 5 minutes 30 minutes
n=9 n=8
Low thrombus adherence presumably XIENCE V: No reduced flow between
due to smooth coating integrity and 5 minutes and 30 minutes porcine in-vivo.
hemocompatibility of the XIENCE V
polymer.
Data on file at Abbott Vascular

25. Stent Thrombosis is Affected by Stent
Design, Deployment and Polymer
Impact of strut thickness and Xience V polymer coating
In vitro pulsatile Chandler loop model with porcine blood
2
Relative platelet cell adhesion
49%↑; P<0.001
LDH Adsorbance for ML VISION (81 µm)
LDH Adsorbance for Stent formulation /
1.8
1.6
1.4
1.2
1.0 24%↓; P=0.002
0.8
0.6
0.4
0.2
0.0
ML VISION (81 µm) TS VISION (162 µm) XIENCE V (96.6 µm)
TS = thick strut
Kolandaivelu K et al. Circulation 2011;123:1400-1409

26. Stent Thrombosis is Affected by Stent
Design, Deployment and Polymer
Impact of stent malapposition
In vitro pulsatile Chandler loop model with porcine blood
P=0.037
P<0.001
LDH Adsorbance for Malapposed Condition
LDH Adsorbance for Approved ML VISION
2 P<0.001 P=ns 64%↑;
1.8 58%↑; P<0.001
1.6 P<0.001 27%↓;
1.4
P=0.04
Similar to
1.2
(81 µm)
apposed XV
1 DES
0.8
0.6
0.4
Apposed Mal-
0.2
ML apposed
0
Vision ML ML VISION ML VISION TS VISION XIENCE V
Vision (81 µm) (81 µm) (162 µm) (69.9 µm)
APPOSED CONTROL MALAPPOSED
Kolandaivelu K et al. Circulation 2011;123:1400-1409

27. EXAMINATION Trial
1504 pts with STEMI undergoing PCI within 48° (85% primary PCI
within 12°) were randomized to Xience V EES vs. Vision BMS
Stent thrombosis (Def/prob) within 1 year
Acute Subacute Late
Vision 2.6%
p = 0.01
Xience V 0.9%
0 1 2 3
Definite ST was reduced with Xience V from 1.9% to 0.5%, p=0.01
Sabate M. ESC 2011

28. Stent Thrombosis Network Meta-analysis
Primary EP: ARC Definite ST (FU through 2 years)
BMS
9 studies
PES FDA
approved
stents
(BMS, SES, PES, End-ZES, Res-
ZES, CoCr-EES, PtCr-EES)
49 RCTs
End-ZES
6 studies
SES 50,844 pts
CoCr-EES CoCr-EES has the lowest rate of
stent thrombosis within 2 years of
implantation.
Res-ZES Pt-Cr-EES
Palmerini T et al. Lancet 2012:On-line