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

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

1st Gen Drug-Eluting Stents

7 years

Late loss = 0

Great Success at follow up after 1st Generation DES implantation

NO RESTNOSIS

1st Gen Drug-Eluting Stents

7 years

Late loss = 0

Great Success at follow up after 1st Generation DES implantation

NO RESTNOSIS = Delayed Vascular Healing

BMS DES

Incomplete Endothelialization Fibrin Persistance

Eos

Giant cells

Inflammation

Polymer Toxi c positive remodeling/

Malapposition

1st Gen Drug-Eluting Stents

7 years

Late loss = 0

Great Success at follow up after 1st Generation DES implantation

NO RESTNOSIS = Delayed Vascular Healing

BMS DES

Incomplete Endothelialization Fibrin Persistance Eos

Giant cells

Inflammation

Polymer Toxi c positive remodeling/

Malapposition

Late stent thrombosis

1st Gen Drug-Eluting Stents

7 years

Late loss = 0

Great Success at follow up after 1st Generation DES implantation

NO RESTNOSIS = Delayed Vascular Healing

BMS DES

Incomplete Endothelialization Fibrin Persistance Eos

Giant cells

Inflammation

Polymer Toxi c positive remodeling/

Malapposition

Late stent thrombosis

PES (N=93

Lesions, 34 142 Struts)

BMS (N=32 Lesions, 9997

Struts) P

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

1st Gen Drug-Eluting Stents

ARC-ST (Definite/Probable) at 5 Years TAXUS I, II-SR, IV & V (n=2,797)

2.3% (n=30)

1.7% (n=22)

5-Year HR [95% CI]: 1.37 [0.79, 2.38]

P=0.26

0%

3%

0 1 2 3 4 5

4%

5%

2%

1% Sten

t thr

ombo

sis

(%) BMS (n=1397)

TAXUS (n=1400)

Years Event Rate ± 1.5 SE Stone GW et al. JACC CV Int 2011;4:530–42

Myocardial Infarction at 5 Years TAXUS I, II-SR, IV & V (n=2,797)

7.7% (n=102)

6.6% (n=89)

5-Year HR [95% CI]: 1.15 [0.87, 1.53]

P=0.33

0%

5%

10%

15%

0 1 2 3 4 5

Myo

card

ial i

nfar

ctio

n (%

)

BMS (n=1397)

TAXUS (n=1400)

Years Event Rate ± 1.5 SE Stone GW et al. JACC CV Int 2011;4:530–42

Myocardial Infarction: Landmark Analysis TAXUS I, II-SR, IV & V (n=2,797)

0%

5%

10%

0 1 2 3 4 5

4.0%

4.5%

2.3%

3.8%

Years Event Rate ± 1.5 SE

1-5 Year HR [95% CI]: 1.67 [1.06, 2.65]

P=0.03 0-1 Year HR [95% CI]:

0.89 [0.62, 1.27] P=0.52

Myo

card

ial i

nfar

ctio

n (%

)

BMS (n=1397)

TAXUS (n=1400)

Stone GW et al. JACC CV Int 2011;4:530–42

SYNTAX 4-year Outcomes • EACTS 2011 • Serruys • October 2011 • Slide 11

SYNTAX 4-year Outcomes • EACTS 2011 • Serruys • October 2011 • Slide 11

0.3

2.6 1.7 1.3 1.4

Patie

nts,

%

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.

Days Postprocedure

Acute ≤1d

Subacute 2-30d

Late 31-365d

Very Late 366-730d 731-1095d 1096-1460d

SYNTAX: ARC Stent Thrombosis

Probable ARC ST (Per Patient) Definite ARC ST (Per Patient)

Total 4 year

8.8

1.1

Serruys PW. TCT 2011

~4.5% ST in year 1

~1.3% ST/yr in years 2-4

HORIZONS-AMI: Stent Thrombosis (ARC Definite or Probable)

P=0.63

3-yr HR [95%CI]= 1.10 [0.74, 1.65]

4.3%

Sten

t Thr

ombo

sis

(%)

0

1

2

3

4

5

6 TAXUS DES (n=2238) EXPRESS BMS (n=744)

4.8%

P=0.72

1-yr HR [95%CI]= 0.92 [0.58, 1.45]

1980 654

2066 2108 695

2238 TAXUS DES

0 12 15 18 21 24 27 30 33 36

744 683

Months 3 6 9

Number at risk

EXPRESS BMS 2013 664

1932 637 425

1341

3.4%

3.1%

Stone GW et al. Lancet 2011;377:2193-204

J Am Coll Cardiol. 1998 Jan;31(1):224-30

0 0 1 2

20

40

60

80

3

100 Y=17.8x + 30.4 r= 0.73 P <0.01 n=21

Neo

intim

a% S

teno

sis

Injury Score

0 0 1 2

20

40

60

80

3

100 Y=16.5x + 31.3 r= 0.66 P <0.01 n=21

Neo

intim

a% S

teno

sis

Inflammatory Score

Score 0 Score 1 Score 2 Score 3

Presented by Renu Virmani

Impact of Strut Thickness on Vascular Healing and Neointimal Formation in BMS

Thick

Thin

(%)

0

20

40

10

30

0

2

Fibrin Score

3

1

% Stenosis Inflammation Score

Thick

Thin

Thick= 162 um Thin= 82 um

Scor

e

28-Days

Rabbit Model: 7-Days

Thick Thin

0

20

40

60

Thin Thick

P= 0.008

Strut Coverage (%)

Strut Thickness Effect on Restenosis Outcome (ISAR-STEREO-2) Trial

Thin-Strut (n = 309)

Thick-Strut (n = 302) p Value

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

Thin-Strut (n = 229)

Thick-Strut (n = 236)

p Value

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

p <0.001

p <0.001

Deep Wall Trauma Reduction

7788

94.83

0

20

40

60

80

100

Express Liberté

Strut Coverage at 14 days in Rabbit

Element

132 μm 97 μm 81 μm

P=0.05

P=0.001

Soucy N, Feygin J et al, EuroIntervention 2011

%

Express Liberté Element

Impact of Strut Thickness on Vascular Healing and Neointimal Formation in BMS

3rd Generation

2nd Generation

1st Generation

Stainless Steel Cobalt Alloys Platinum Chromium PLLA

Xience V® Stent

Cypher® Stent

Endeavor® Stent

TAXUS® Liberté®

Stent

TAXUS® Express®

Stent

Xience Prime® Stent

SYNERGY™ Stent

BVS

0.081 mm (0.0032”)

0.091 mm (0.0036”)

0 .081 mm (0.0032” )

0.140 mm (0.0055” )

0.096 mm (0.0038”)

0.132 mm (0.0052”)

0.081 mm (0.0032”)

0.074 mm (0.0029”)

0.150 mm (0.0059”)

4th Generation

1st Gen BVS

Progression in Stent Platform Design Strut Thickness and Biomaterials

SPIRIT II, III, IV and COMPARE trials Pooled database analysis (n=6,789)

Stent thrombosis (ARC definite/probable)

4247 4177 4082 3479 2542 2463 2408 2110

Number at risk XIENCE TAXUS

2.3%

Sten

t thr

ombo

sis

AR

C d

ef o

r pro

b (%

)

0

1

2

3

Time in Months 0 3 6 9 12 15 18 21 24

3998 2350

0.7%

p<0.001 HR: 0.30 [0.19, 0.47] EES (n=4,247)

PES (n=2,542)

Kereiakes DJ et al. EuroIntervention 2011:7:74-83

SPIRIT II, III, IV and COMPARE trials Pooled database analysis (n=6,789)

Stent thrombosis (ARC def/prob) at 2 years

Planer D et al. JACC Cardiovasc Interv. 2011;4:1104-15

0.25 (0.12–0.52) P=0.0002 0.34 (0.19–0.62)

P=0.0002

14 Day Endothelialization: Rabbit Iliac Model XIENCE V CYPHER TAXUS ENDEAVOR

Joner M et al. JACC 2008;52:333-42

CD31: Green Channel

Over Struts

Between Struts

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™

Joner M et al. JACC 2008;52:333-42

Ting-Yu Liu et al. Polym. Adv. Technol. 2005;16:413–419

The Concept of Fluoropassivation Fluoropolymer coated surfaces are

thromboresistant in blood-contact application

Platelet adhesion onto different polymeric surfaces after 15 min exposure to blood at 150 rpm (37° C).

Platelet count measured using 51Cr method.

Massa TM et al. J Biomed Materials Research Part A DOI 10.1002/jbm.a

3000

2500

2000

1500

1000

500

0 BASE PP0212L PTM0212F PTM0212I

Plat

elet

s / m

m2

30 min 60 min 120 min

Thro

mbu

s Fo

rmat

ion

(%)

20

PAN PAN91 PAN82 PAN73 PVDF

Comparison of thrombus formation ratio of PAN/PVDF blend membranes after 30, 60 and

120 min incubation (n=3).

18

16

14

12

10

8

6 4

2

0

Biocompatibility XIENCE V – Thromboresistant

Data on file at Abbott Vascular

3138

211

752 871

0

500

1000

1500

2000

2500

3000

3500

4000

XIENCE V (n = 10) Endeavor (n = 8) Cypher (n = 8) Taxus Liberte (n = 8)Wei

ght o

f Thr

ombu

s (µ

g) A

dher

ed o

n St

ent

p = 0.02

p = 0.003

p = 0.0001

Chandler Blood Loop Test (2 h Exposure)

Hemocompatible Polymer Unheparinized Ex-Vivo Shunt Study

Low thrombus adherence presumably due to smooth coating integrity and hemocompatibility of the XIENCE V

polymer.

0.00

0.05

0.10

0.15

0.20

0.25

XIENCE V VISION

Avg

. Wei

ght I

ncre

ase

(g)

XIENCE V: No reduced flow between 5 minutes and 30 minutes porcine in-vivo.

n=9 n=8

0

50

100

150

200

5 minutes 30 minutes

Blo

od F

low

(mL/

min

)

XIENCE V n=9

VISION n=8

Data on file at Abbott Vascular

Stent Thrombosis is Affected by Stent Design, Deployment and Polymer

Kolandaivelu K et al. Circulation 2011;123:1400-1409

Impact of strut thickness and Xience V polymer coating In vitro pulsatile Chandler loop model with porcine blood

Rel

ativ

e pl

atel

et c

ell a

dhes

ion 49%↑; P<0.001

24%↓; P=0.002

2

1.8

1.6

1.4

1.2

1.0

0.8

0.6

0.4

0.2

0.0 ML VISION (81 µm) TS VISION (162 µm) XIENCE V (96.6 µm)

LDH

Ads

orba

nce

for S

tent

form

ulat

ion

/ LD

H A

dsor

banc

e fo

r ML

VISI

ON

(81

µm)

TS = thick strut

Stent Thrombosis is Affected by Stent Design, Deployment and Polymer

Kolandaivelu K et al. Circulation 2011;123:1400-1409

Impact of stent malapposition In vitro pulsatile Chandler loop model with porcine blood

Apposed ML

Vision

Mal- apposed

ML Vision

58%↑; P<0.001

64%↑; P<0.001

27%↓; P=0.04

Similar to apposed XV

DES

ML VISION (81 µm)

ML VISION (81 µm)

APPOSED CONTROL

1.6

LDH

Ads

orba

nce

for M

alap

pose

d C

ondi

tion

LDH

Adso

rban

ce f

or A

ppro

ved

ML

VISI

ON

(81

µm)

1.8

2

1.4

1.2

1

P=0.037

0.8

0.6

0.4

0.2

0

P=ns P<0.001 P<0.001

TS VISION (162 µm)

XIENCE V (69.9 µm)

MALAPPOSED

EXAMINATION Trial

0 1 2 3

Xience V

Vision

Acute Subacute Late

p = 0.01

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

2.6%

0.9%

Definite ST was reduced with Xience V from 1.9% to 0.5%, p=0.01 Sabate M. ESC 2011

Palmerini T et al. Lancet 2012:On-line

9 studies PES BMS

SES End-ZES

Res-ZES Pt-Cr-EES

CoCr-EES

6 studies

Stent Thrombosis Network Meta-analysis Primary EP: ARC Definite ST (FU through 2 years)

FDA approved

stents

(BMS, SES, PES, End-ZES, Res-ZES, CoCr-EES, PtCr-EES)

49 RCTs

50,844 pts

CoCr-EES has the lowest rate of stent thrombosis within 2 years of

implantation.