Vo Thanh NhanCap nhat DES 2010

Cập nhật về stent phủ thuốc

PGS Võ Thành Nhân
ĐH Y Dược – BV Chợ Rẫy TpHCM


Percutaneous Coronary Intervention:
Progressive improvements in success, safety, and durability
as serial new technologies have been launched.
40

Event Rate %

Failure
Em CABG

30

Restenosis
Stent
thrombosis
VLST

20

10

0

POBA early POBA late Stent early Stent late
1977

1985

1994

1997

Innovations over time
Dr. Don Baim, FDA Panel Meeting December 2006

DES
2003-present


Expanding Clinical Knowledge in DES
multi-vessel
disease
bifurcated
lesions
•SYNTAX
AMI

•FREEDOM
•SYNTAX
•CORPAL-BIF

ISR

small
vessels

work
-horse
•TAXUS IV
•TAXUS V
•REALITY
-TAXUS
•RAVEL
•SIRIUS
•REALITY
-CYPHER

•TAXUS V
•REALITY
-TAXUS
•SES-SMART
•ISAR
-SMART

long
lesions
•TAXUS VI
•TAXUS V
•Park LL2

diabetes
•TAXUS VI
•TAXUS V

•Horizons

•TAXUS V ISR
•SISR
•RIBS II
•ISAR
-DESIRE

•TAXUS IV
-DIABETES
•CARDIA
•ISAR
-DIABETES

Increasing complexity

left main
disease
•SYNTAX


Increase in Complexity of PCI-treated Patients
Challenges technology for continuing improvements

Left Main
Three Vessels

CTO
CABG
PCI

Complexity

Bifurcation
Two Vessels
Small Vessels
Long Lesions
Single Vessel

Time

Today


Advancing DES technology

Drug Eluting Stents,…
a delivery balloon and catheter, a polymer
(or not!), a stent platform and a drug
...all can be
better.


International Drug-Eluting Stent Projected Timelines
2003 through 2013+ Projections*
2003

2004

2005

2006

TAXUS™
Express™
Stent

2007

2008

2009

TAXUS™
Liberté™
Long

BSC

JNJ

2011

2012

TAXUS™
Element™
Stent

TAXUS™
Liberté™
Stent

PROMUS™
Element™
Plus
Stent**

PROMUS™
Element™
Stent

Cypher™
Stent

2013+

Metallic
Bioabosrbable
Stent***
Element
Bare
Stent***

PROMUS™
Stent

MDT ABT

2010

Polymer

Bioabosrbable
Stent***

Synergy
Program***

NEVO™
Stent***

XIENCE V™
Stent

Endeavor™
Stent

Endeavor™ Endeavor™
Sprint
Resolute
Stent**
Stent

XIENCE
Prime™
Stent

XIENCE
ThinMan
Stent***

Integrity™

Stent**

*Estimated launch dates as of March 2010. TAXUS™ Element™ Stent Pending CE Mark, not for sale in EEA, U.S. or Japan. **CAUTION: Investigational device. Limited
to investigational use. PROMUS Stent is a private-labeled XIENCE V™ Everolimus Eluting Coronary Stent System manufactured by Abbott and distributed by Boston
Scientific Corporation. ***Concept device. Not for sale. Based on CVpipeline database and internal estimates. Data provided for information purposes only, not meant as
a promotional tool nor as an indicator of regulatory approvals. BSC internal estimates

Integrity™
DES
Stent**

BVS
Stent***


Thin Strut Impacts Clinical Outcomes
Historical Data with Bare Metal
Reduce deep wall trauma

ISAR STEREO1

ISAR STEREO2

6 month binary restenosis

6 month binary restenosis

Thin Thick
Multi-link™

Thin Thick
Multi-link™

Strut thickness appears to have a significant
impact on long-term restenosis after stent
implantation.1,2

1ISAR

STEREO II JACC Vol. 41, No. 8, 2003 April 16, 2003:1283-8. 2ISAR STEREO I Circulation June 12, 2001


SCAAR Registry
DES Results at 3 Years (Adjusted)

Probability of Restenosis

8%

TAXUS™ Express2™ Stent vs. TAXUS™ Liberté™
Stent
1.24 (1.05 - 1.47) HR(95%C.I.)

6%

4%
EndeavorTM Stent N=3,531

2%

TAXUSTM Express2TM Stent N=9,629
CypherTM Stent N=11,282
TAXUS™ LibertéTM Stent N=11,036

0%
0

1

Years After PCI
Presented by B. Lagerqvist MD, ESC 2008.

2


TAXUS™ ATLAS
Studies

TAXUS™ ATLAS Small Vessel Study
TLR results at 3 years2
25.00%

0.5

0.44 mm
P = 0.03

0.4

0.28 mm

(mm)

0.3

12

0.1

5.00%

10.4 %
P = 0.01

1.Dr M Turco et al. J Am Coll Cardiol Intv 2008;1:699 –709 2. TAXUS
ATLAS Clinical
2.Program sponsored by Boston Scientific, Data on file. 3 year data
presented by 1.Dr M Turco at TCT 2009.

TLR at 3 years

MI/ST results at 3 years2
8.1%

3.9 %

2.9 %
1.5 %

2

TAXUS™
Express2TM
TAXUS™ Liberte™

0.00%

P = 0.01

6
4

10%

TAXUS™ ATLAS Long Lesion Study

10
8

15.00%
10.00%

Instent Late Loss at 9
Months

P = 0.008

20.00%

0.2

0

Percent

Given that the 2 stents
use the same stent
material, polymer
coating, drug dose, and
release kinetics, the
observed clinical
benefits are likely the
result of the more
uniform strut pattern
and thinner strut
design.1

22.10
%

P=0.03

0%

0
Total MI

NQWMI

Stent
Thrombosis

ARC ST
Definite/
Probable


Taking the Challenge-Platform Development
Paclitaxel and Everolimus Eluting Stents
2003 2004 2005 2006

2007 2008 2009 2010

Timeline Reflects CE Mark Approval (Actual or Anticipated dates)

TAXUS™
Express™ Stent

TAXUS™
Liberté™ Stent

TAXUS™
Element™ Stent

PROMUS™
Stent

PROMUS™
Element™ Stent

The Element™ Stent Series
Three new components
Alloy
Platinum Chromium

Stent Design
Element

Catheter
Improved Deliverability

● Designed for coronary stenting

● Thin struts - 0.0032” (.081mm)

● New balloon system

● improve radiopacity

● New geometry, 4 stent models

● Robust shaft – push and flex

● low recoil, high radial strength

● improved conformability

● Low profile

Bench test results may not necessarily be indicative of clinical performance. Data on file at BSC.

Platinum Chromium Technical Bulletin 90353760


The Element™ Stent Series is made of platinum
chromium, an alloy created specifically for
coronary stenting
• Platinum is 2 times more dense than Iron or Cobalt
• Platinum is a solid solution strengthener (when alloyed with 316L SS)
• Platinum is malleable & corrosion resistant
• Platinum is fully incorporated in the alloy (not just a coating)

Bench test results may not necessarily be indicative of clinical performance. Data on file at BSC.


Platinum Chromium (PtCr) and Radiopacity

Density Values
11
9.9

10

9.1
g/cc

9

8.4
8.0

8
7
6

316L Stainless
Steel

Platinum
Chromium
Alloy

L605
MP35N
(Cobalt
(Cobalt
Chromium) Chromium)

Bench test results may not necessarily be indicative of clinical performance. Data on file at BSC.
Images property of BSC.


Element™ Stent Series Strut Thickness
38% reduction in strut thickness compared to the TAXUS Express
Stent and 16% compared to the TAXUS Liberté Stent
TM

TM

0.140 mm

0.132 mm

.096 mm

.091 mm

Bench test results may not necessarily be indicative of clinical performance. Data on file at BSC. Images property of BSC.

TM

.081 mm

.081 mm

TM


Element™ Stent Series
Radial Strength

Radial Strength
Amount of Radial Force Required to Reduce the Diameter of a Deployed Stent
0.30

Better
0.26

0.25

0.24

(Newtons/mm)

Radial Force

0.20
0.17
0.15

0.14
0.11

0.10
0.05
0.00
TAXUS™ Element™

PtCr Alloy

TAXUS™ Liberté™

Stainless Steel
Alloy

Cypher™

Stainless Steel
Alloy

Endeavor™

CoCr Alloy

Testing Completed by Boston Scientific. Data on File.Testing completed by Boston Scientific (2.5mm Stent Products.
TAXUS Element n=15, Xience V n=10, Endeavor n=3, TAXUS Liberté n=8, Cypher n=3. Data on file. Bench test results
may not necessarily be indicative of clinical performance.

Xience V™

CoCr Alloy


Element™ Stent Series
Minimize Recoil

Post Expansion Stent Diameter Recoil
Percentage the stent diameter decreases after balloon deflation

Better
6
5.1

Percent (%) Recoil

5

4.6

4
3.4

3.0

3

2.8

2
1
0
Endeavor™

CoCr Alloy

Xience V™

CoCr Alloy

Cypher™

Stainless Steel
Alloy

TAXUS™ Element™

PtCr Alloy

Testing Completed by Boston Scientific. Data on File.Testing completed by Boston Scientific (2.5mm Stent Products.
TAXUS Element n=15, Xience V n=10, Endeavor n=3, TAXUS Liberté n=8, Cypher n=3. Data on file. Bench test results
may not necessarily be indicative of clinical performance.

TAXUS™ Liberté™

Stainless Steel
Alloy


Element™ Stent Series
Conformability

Conformability
Measures the ability of the stent to naturally conform to the vessel

1.20
1.00

1.00

Better

Newtons.mm

0.80
0.60
0.40
0.30

0.20
0.09

0.06

0.04

Endeavor™
CoCr Alloy

TAXUS™ Element™
PtCr Alloy

0.00
Cypher™
Stainless Steel
Alloy

Xience V™
CoCr Alloy

TAXUS™ Liberté
Stainless Steel
Alloy

Testing Completed by Boston Scientific. Data on File.Testing completed by Boston Scientific (2.5mm Stent Products.
TAXUS Element n=15, Xience V n=10, Endeavor n=3, TAXUS Liberté n=8, Cypher n=3. Data on file. Bench test results
may not necessarily be indicative of clinical performance.


Effect of Platform on Re-Endothelialization
BMS Express™ vs. Liberté™ vs. Element™ Stents
% Uncovered Struts (14 Days)
25

% Uncovered Struts (21 Days)
25

23.1

20

20
p=0.07 vs Express

15

15

13

10

p=0.1 vs. Liberté
p=0.001 vs Express

4.4

5
0

10
5

4.9

p=0.3 vs Express

1.7

p=0.4 vs. Liberté
p=0.6 vs Express

3.4

0
Express ™

Liberte™

Element™

Express™

Kinetics of strut coverage impacted by stent platform

Bench test results may not necessarily be indicative of clinical performance. Data on file at BSC.

Liberte™

Element™


Comparison of ELEMENT™ and Multi-Link

BMS Stent
Rabbit Endothelialization Model
Element™

Vision™

14 Days
Images provided by Renu Virmani, MD

Element™

Vision™

28 Days


The Element™ Stent Series
Consistent drug distribution
TAXUS™ Express™
Stent

TAXUS™ Liberté™
Stent

TAXUS™ Element™
Stent

Computer modeling of drug distribution uniformity in vascular tissue. Dark blue = low levels of drug
concentration and red = high levels of drug concentration.

Testing by Boston Scientific. Data on File. Computer modeling of drug distribution uniformity in vascular
tissue. Dark blue = low levels of drug concentration and red = high levels of drug concentration. Modeling
results are for demonstration purposes only and may not necessarily be indicative of clinical performance.


Dual Drug Program
TAXUS™ Element™
Stent

PROMUS™ Element™
Stent

Paclitaxel

Everolimus

Element™ Platform

Element™ Platform

Images property of Boston Scientific Corporation


TAXUS™ Element™ and the TAXUS™ Liberté™ Stent
Histologically indistinguishable at 28 and 180 days
28 Days

TAXUS™ Element™

TAXUS™ Liberte™

180 Days

TAXUS™ Element™

TAXUS™ Liberte™

There were no differences between groups for:
•all morphometric parameters (EEL area, medial area, IEL area, lumen
area and percent stenosis)
•all morphologic parameters (thrombus, endothelialization,
inflammation, IEL disruption, EEL disruption, medial SMC loss, PAM, and
strut coverage)


Trial Design
PERSEUS WH

PERSEUS Workhorse (WH), ≥2.75mm - ≤4.0mm, ≤28mm
NON-INFERIORITY Design, Randomized 3:1
TAXUS™ Element™
Paclitaxel-Eluting Stent
(N=942)

TAXUS™ Express™
Paclitaxel-Eluting Stent
(N=320)

Primary Endpoint: TLF* (12 mos)
Secondary Endpoint: in-segment %DS (9 mos)**

*TLF=ischemia-driven TLR or MI/cardiac death related to target vessel

**QCA cohort randomly assigned

Statistical Methods
 Bayesian analysis used to power the 1o and 2o endpoints
 Success criteria: ≥95% Bayesian probability that TAXUS
Element Stent is non-inferior to TAXUS Express Stent
 Predefined delta: 4.1% (TLF); 0.20 ln (%DS)*
 Standard (frequentist) method used for all other endpoints
Presented by Dean J. Kereiakes, MD at ACC 2010


12-Month Clinical Outcomes
PERSEUS WH

TAXUS™ Express™ Stent (N=320)
TAXUS™ Element™ Stent (N=942)

P=0.78

P=0.48

P=0.60

5.6
4.5

5

0
Pts at 313
922
TLF
risk

2.9
0.3

0.5

313

922

Cardiac
Death

313

3.8

2.2

MI

922

313

TLR

922

Page 24 of 32

6.1

P>0.99

5073 March 2010

Event Rates (per Patient, %)

10

*12m DAPT compliance 89%, both groups

Presented by Dean J. Kereiakes, MD at ACC 2010 .*TLF: ischemia-driven TLR, or MI/cardiac death related to the target vessel.
Not intended for use in the United States. Please see glossary. © 2010 Boston Scientific Corporation or its affiliates. All rights reserved.


12-Month Clinical Outcomes - Safety
PERSEUS WH

TAXUS™ Express™ Stent (N=320)

TAXUS™ Element™ Stent (N=942)

P>0.99

P>0.99

P=0.48

P=0.34

P=0.17

P>0.99

5

0.3 0.5

0.6 0.7

0
Pts at 313 922
risk Cardiac
Death

314 922
All
Death

2.9

2.2

1.6
0.0

313

922
MI

0.5

313 922
Q-Wave
MI

0.3 0.4
313 922
Non-Q
MI

313 918
ST*

ARC
Def/Prob

Page 25 of 32

2.9

5073 March 2010

Event Rates (per Patient, %)

10

*12m DAPT compliance 89%, both groups
Presented by Dean J. Kereiakes, MD at ACC 2010

Not intended for use in the United States. Please see glossary. © 2010 Boston Scientific Corporation or its affiliates. All rights reserved.