zomaxx: abbott's drug eluting stent programme · nir 7 cell bard xt crossflex lc wallstent...

ZoMaxx: Abbott's Drug Eluting Stent Programme

John OrmistonGreen Lane and Mercy Hospitals

Auckland, New Zealand

ZoMaxx Drug-Eluting StentZoMaxx Drug-Eluting Stent

TriMaxxStent

Platform

TriMaxxStent

Platform

PharmaCoatPolymerCoating


ABT-578ABT-578

ZoMaxx™

Drug-ElutingStent

ZoMaxx™

Drug-ElutingStent

TriMaxx Stent PlatformTriMaxx Stent Platform

88--10 cells/ 10 cells/ perimeterperimeter

2 connectors/ 2 connectors/ circumferencecircumference

OffOff--set crown set crown connector connector

Stent Scaffolding(Mean interstrut diameter)Stent Scaffolding

(Mean interstrut diameter)

0.0

0.2

0.4

0.6

0.8

1.0

1.2

Driver TriMaxx Express 2 Vision BX Sonic

Scaf

fold

ing

Dia

met

er (m

m)

Data on file at Abbott Vascular Devices

Driver is a trademark of Medtronic; Express2 is a trademark of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & JohnsonDriver is a trademark of Medtronic; Express2 is a trademark of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & Johnson

Triplex is a trademark of Uniform Tubing, Inc.

Currently in development at Abbott Vascular Devices, not to be distributed or reproduced without permission of Abbott Vascular Devices

Tantalum provides strength and increased Tantalum provides strength and increased radioopacityradioopacityIt allows struts to be thinner without sacrificing It allows struts to be thinner without sacrificing strength or strength or radioopacityradioopacity

Triplex stent material3 layered composite

Strut thickness 0.0029”

Tantalum layer 0.0029”

Stainless steelStainless Stainless steelsteel

Stainless steelStainless Stainless steelsteel

TantalumTantalumTantalum

Stent Material andStrut Thickness

Stent Material andStrut Thickness

0.0000

0.0010

0.0020

0.0030

0.0040

0.0050

0.0060

TriMaxx Vision Driver Liberte Express 2 BX Sonic

Triplex™Triplex™

Stainless SteelStainless Steel

Lab

eled

Thi

ckne

ss (i

nche

s)


Driver is a trademark of Medtronic; Express2 & Liberté are trademarks of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & Johnson; Triplex is a trademark of Uniform Tubing, Inc.Driver is a trademark of Medtronic; Express2 & Liberté are trademarks of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & Johnson; Triplex is a trademark of Uniform Tubing, Inc.

Cobalt ChromeCobalt Chrome

0

50

100

150

200

250

300

Strut Thickness (inches)

TantalumCobalt ChromeCobalt AlloyStainless SteelTriplex™

TantalumCobalt ChromeCobalt AlloyStainless SteelTriplex™

0.001” 0.002” 0.003” 0.004” 0.005”

MultiLink

Wiktor

Rad

iopa

city

Vision

PentaZeta

Driver Express2

Bx SonicTriMaxx

RadiopacityStrut thickness is less without sacrifice of radio-opacity

RadiopacityStrut thickness is less without sacrifice of radio-opacity


Driver is a trademark of Medtronic; Express2 is a trademark of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & Johnson; Triplex is a trademark of Uniform Tubing, Inc.Driver is a trademark of Medtronic; Express2 is a trademark of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & Johnson; Triplex is a trademark of Uniform Tubing, Inc.

Liberté

Calibrated travelling microscope

3 points along 3 examples of each stent/delivery system

Independent Measurement of Stent/Delivery System Profile

(Diameter)

OrmistonOrmiston CCVI 2000Ormiston CCVI 2000

Ormiston

Stent Delivery System Crossing Profile

0.9

1

1.1

1.2

1.3

1.4

1.5

1.6

Tsunami

Liberte

Trimaxx

Driver

Antares

DISA

S-Flex

Duraflex

Sonic

Zeta

Bx

Velocity

Jo Stent flex

Vision

Express 2

Tetra

NirR

oyal

Penta

Tristar

Duet

BiodivYsio

S670d

BeStent2

Express

S7 Nir7 C

ell

Bard XT

Crossflex

LC

Wallstent

Wiktor I

Ave G

FX

Multilink

Dia

met

er (m

m)

FStiffness was measured using a 3 point

bend test

rr

Ormiston Cathet CardiovInterv 2000

(Instron)

Forc

e

Displacement

stiff

Less stiff

1Flexibility =

stiffness

The slope of the Force/Displacement curve is Stiffness

Stiffness is the reciprocal of Flexibility

Ormiston

Ormiston

Stiffness (reciprocal of flexibility)

0

20

40

60

80

100

120

140

160W

ikto

r

Bar

d X

TTr

imax

x

Cro

ssFl

ex

Driv

er

Tsun

ami

AV

E G

FX

Mul

tilin

k

Visi

on

Libe

rte

Due

t

Exp

ress

Exp

ress

II S7

Tris

tar

Zeta

Pen

ta

Wal

lste

nt

Tetra

S670

d

Dur

afle

x

Bio

divY

sio

Jo S

tent

DIS

A S

-Fle

x

BeS

tent

2

Bx

Vel

ocity

Ant

ares

Nir

7 C

ell

Nir

Roy

al

gms

forc

e/m

m

Expanded Mounted

Stent FlexibilityStent Flexibility

Driver is a trademark of Medtronic; Express2 is a trademark of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & JohnsonDriver is a trademark of Medtronic; Express2 is a trademark of Boston Scientific; Vision is a trademark of Guidant; Bx Sonic is a trademark of Johnson & Johnson

In Vitro Bench TestingIn Vitro Bench Testing

10g

Bx

10g

OC

10g

Express2

10g

Vision

10g

Driver

10g

TriMaxx


Stent radial strength is needed especially in calcified, fibrotic, or ostial lesions to:

Resist compressive forcesMaintain sizeMaintain circular shape

Ormiston

IVUS

tecoflex

Stentpp

PRESSURE CHAMBERPRESSURE CHAMBERPRESSURE CHAMBER

Water

Ormiston

70

80

90

100

110

0 0.5 1 1.5 2 2.5 3

PRESSURE (Atmos)

% C

RO

SS-S

ECTI

ON

AL A

REA

% AREA and EXTERNAL PRESSURE(IVUS on benchtop)

Stent DStent D

Stent XStent X 10%

25%

Ormiston

Radial Strength: External Pressure and Stent Cross-sectional Area Reduction

0.0

0.5

1.0

1.5

2.0

2.5

3.0

BeS

tent

Biodivysio

JoStent

Multilink

NIR

9

Crow

n

V-Flex

Be S

tent 2

Bx Velocity

Trimaxx

Crossflex

Penta

Tsunami

Vision

Driver

Liberte

S7

Express

Duet

Tetra

Duraflex

Pres

sure

(bar

)

Mean 10% Mean 25% Collapse

Ormiston

Is the Zomaxx Stent Platform suitable for Bifurcation stenting

in the DES era?

• Stents were deployed in a phantom using contemporary bifurcation techniques

• Stents were photographed externally and internally

Ormiston

““CrushCrush”” Technique with Technique with ZomaxxZomaxx

Main Main brbr

Side Side brbr


Deploy Deploy sideside--brbrstentstent


Deploy main Deploy main brbrstent crushing stent crushing sideside--brbr stent in stent in main main brbr


2 layers2 layers

3 layers3 layers


““KissingKissing”” balloon balloon postpost--dilatationdilatation

2 layers2 layers

3 layers3 layers

Kissing balloon post-dilatation releases the side-branch from “jail”after “Crush” Bifurcation Stenting

Ormiston

Before Before ““kisskiss””SideSide--brbr jailjail

After After ““kisskiss””No Side No Side brbr jailjail

“Kissing” balloon post-dilatation after “crush” fully expands the Zomaxx stent at the side-br ostium and

corrects any main br distortion

OrmistonNo obstruction to main No obstruction to main brbr No Side No Side brbr jailjail

Well expanded Well expanded at sideat side--brbrostiumostium

The “Culotte” Technique-Provisional side-br stenting in the DES era

Ormiston 04

Trimaxx Stent after “Culotte” Bifurcation followed by “kissing” balloon post-dilatation

OrmistonMain Main brbr Side Side brbr

Trimaxx Trial (BMS)

• 100 patients to receive Trimaxx (BMS)• Single-vessel, de novo coronary lesions (Type A-

B), length > 10 mm and < 15 mm; RVD 3.0-3.75 mm

• Brazil, Germany• PI: Alex Abizaid• Primary Endpoint: MACE at 30 days• Secondary Endpoints: MACE, TLR, TVR,

ABR, Late Loss at 6 months


TriMaxxStent

Platform

TriMaxxStent

Platform



ABT-578ABT-578

ZoMaxx™

Drug-ElutingStent

ZoMaxx™

Drug-ElutingStent

Hema-PC Lauryl HPM & SMT

Polymer- PC Technology™Polymer- PC Technology™

• PC Technology™ mimics body’s own chemistry

– Hema-PC: Mimics outer membrane of red blood cell for biocompatibility

– Lauryl: Hydrophobic for stability and adhesion to the stent surface

– Hydroxypropyl Methacrylate(HPM) & TrimethoxysilylMethacrylate (SMT): Cross-linking for durability

• Following drug elution, PC coating remains bio-inert and non-inflammatory

( ) 2 3( ) 4 7

( ) 2 5( ) 5

OO

OP

O-O O

N +

OO

OO

O H

OO

SiO C H 3O C H 3

H 3 C O

PC Technology is a trademark of Biocompatibles, Inc.

Presented by N. Chronos, TCT 2004, Washington, DC

Effect of PC coating on Inflammationin Porcine Coronary arteries

Effect of PC coating on Inflammationin Porcine Coronary arteries

0.00

0.50

1.00

1.50

2.00

0 30 60 90 120 150 180

Days after implantation

Infla

mm

atio

n Sc

o Bare Triplex (n=8)

PC-coated Triplex (n=8)

0.00

0.50

1.00

1.50

2.00

0 30 60 90 120 150 180


Infla

mm

atio

n Sc

o Bare Triplex (n=8)




Effect of PC coating on Neointimal Hyperplasia in Porcine Coronary

Arteries

Effect of PC coating on Neointimal Hyperplasia in Porcine Coronary

Arteries

0%

10%

20%

30%

40%

50%

0 30 60 90 120 150 180


Are

a St

enos

is (%

)Bare Triplex (n=8)


0%

10%

20%

30%

40%

50%

0 30 60 90 120 150 180


Are

a St

enos

is (%

)Bare Triplex (n=8)




The ZoMaxx Stent - PharmaCoatThe ZoMaxx Stent - PharmaCoat

Not approved for sale in or outside the United States.

PC topcoat

PC basecoat

ABT-578

Presented by L. Schwartz, TCT 2004, Washington, DC

Comparison of in vivo Elution RatesRabbit iliac models

Comparison of in vivo Elution RatesRabbit iliac models

Presented by A. Carter, ACC 2003, presented by B. Chevalier, PCR 2004, data on file at Abbott Vascular Devices

0

20

40

60

80

100

120

0 10 20 30Time (days)

% D

rug

elut

ed

ZoMaxx™Cypher™

0

20

40

60

80

100

120

0 10 20 30Time (days)

% D

rug

elut

ed

ZoMaxx™Cypher™

0

20

40

60

80

100

120

0 10 20 30

Time (days)

% D

rug

elut

ed

0

20

40

60

80

100

120

0 10 20 30

Time (days)

% D

rug

elut

ed Endeavor™No top coat

~75% elution in 2 days100% elution in 10 days

~75% elution in 10 days100% elution in 30 days


TriMaxxStent

Platform

TriMaxxStent

Platform



ABT-578ABT-578

ZoMaxx™

Drug-ElutingStent

ZoMaxx™

Drug-ElutingStent

O

HO OO

ON O

O

O HO

O

OO

HO42

O

HO OO

ON O

O

O HO

O

OO

NNN

N42

FKBP BindingDomain

mTOR EffectorDomain

Rapam ycin

ABT-578

Rapamycin

ABT 578

Tetrazole ring at C42

ABT 578 is different from rapamycindue to Tetrazole group on C42

MM

GG22

GG11

SS

GG00cytostatic agentsallow cells inG0 to re-enterthe cell cycle

ABT-578 is cytostatic: blocks entry into S phase as does sirolimus

CheckpointCheckpoint

DNA synthesisprepares for mitosis

mitosis

cell responds togrowth factor stimulation

Delivered locally, ABT-578 inhibits inflammation and the proliferation of SMCsABT-578 is cytostatic by halting the cell cycle in the late G1 phase

The cell cycle and action of ABT 578

Neointimal Area (mm2)

TriMaxx Taxus Cypher ZoMaxx0

1

2

3m

m2

9 18 18

* ** **

18

*p<0.05 vs. TriMaxx

**p<0.01 vs. TriMaxx

Effect of TriMaxx, ZoMaxx, Cypher, and Taxus Stents on Swine Coronary Morphometry at 28 days (mean + SEM)

Lipophilicity of Some Clinical DES AgentsLipophilicity of Some Clinical DES Agents

Determination of Partition Coefficients for ABT-578, Rapamycin, Paclitaxel, Dexamethasone, and Estradiol at 22 deg C, Abbott Laboratories Report on File, 2004

0

5000

10000

15000

20000

25000

30000

35000

40000

45000

1

P (C

octa

nol/C

Wat

er)

ABT-578 Rapamycin

n=16 n=16

Estadiol Dexamethasone

n=9 n=10

Paclitaxel

n=10

P<0.0001ABT-578 is 2.2 times more lipophilic than rapamycin

Lipophilicity increases tissue retention of the drug


Rabbit Study – Preliminary resultsComparison of Drug Levels in Arterial

Tissue for ZoMaxx Stent versus Cypher Stent

Rabbit Study – Preliminary resultsComparison of Drug Levels in Arterial

Tissue for ZoMaxx Stent versus Cypher Stent

0

20

40

60

80

100

120

140

160

0 5 10 15 20 25 30

Time (days)

Dru

g in

Tis

sue

( ug

/ g )

ZoMaxx™Cypher™

Mean ± SEMn = 4


Cypher is a trademark of Johnson & JohnsonCypher is a trademark of Johnson & Johnson


bc3

슬라이드 42

bc3 the ratio between abt and sirolimus uptake in the first 4 days is around 10:1, are we sure that is safe?Bernard, 2004-05-12

Zomaxx I Trial

• 400 patients to be randomized to receive either a Zomaxx stent or a Taxus stent

• Non-inferiority trial• Primary end-point is late loss 9 month angio• Single de novo lesions • > 10 mm and < 30 mm, RVD 2.5-3.5 mm• 35 sites New Zealand, Australia, Europe• PI Bernard Chevalier

161 of 400 pts enrolled as of 15.4.05

Zomaxx II Trial

• 1670 patients will be randomized to receive either a Zomaxx stent or a Taxus stent

• Non-inferiority trial• Primary end-point is TVR• Single de novo lesions• 75 sites USA and Canada

ZOMAXX I and II Core labsZOMAXX I and II Core labs

Data Center– Harvard Clinical Research Institute, Boston

QCA – Brigham and Women’s, Boston

IVUS – Stanford Interventional Cardiology, Palo Alto

ECG – Harvard Clinical Research Institute, Boston

Presented by A. Yeung, TCT 2004, Washington, DC

Summary

• Zomaxx Stent– Trimaxx stent has excellent mechanical and

physical properties– PharmaCoat polymer safe– ABT 578 – Drug release rate similar to Cypher

• Trials -Zomaxx I underway, ZomaxxII planned

Single, de novo coronary lesions (Type A-B)with length > 10 mm and < 30 mm,

and RVD 2.5-3.5 mm.Pre-dilatation required

TAXUS™ StentN=200

ZoMaxx™ StentN=200

8, 18, 23, 33 mm 8, 18, 23, 33 mm 3.0 mm3.0 mm

8, 18, 23, 28 mm 8, 18, 23, 28 mm 2.5 mm2.5 mm

8, 18, 23, 33 mm 8, 18, 23, 33 mm 3.5 mm3.5 mm

Stent Lengths Stent Lengths Stent DiametersStent Diameters

30d 6mo 9mo 12mo 2yr 3yr 4yr 5yr

ZOMAXX I TrialRandomized, Non-inferiority Trial vs Taxus

ZOMAXX I TrialRandomized, Non-inferiority Trial vs Taxus

Clinical follow-up

Radiographic follow-up QCA/IVUS

N=40034 sitesEuropeAustraliaNew Zealand

Primary endpoint: 9-mos. in-segment late loss with equivalency limit of 0.25 mm, σ=0.4 mm;> 99% power; 1-sided α=0.05

Secondary endpoints: MACE, TVF, TLR, TVR, binary restenosis, in-stent late loss, neointimal volume, neointimal volume obstruction

Medications: Clopidogrel 75 mg QD for at least 6 months, ASA 100 mg QD ≥ 12 monthsStratification: Site


Single, de novo coronary lesions (Type A-B)with length > 10mm and < 28mm

and RVD 2.5-3.75mmPre-dilatation required

TAXUS™ StentN=835

ZoMaxx™ StentN=835

8, 13, 18, 23, 33 mm 8, 13, 18, 23, 33 mm 3.0 mm3.0 mm

8, 13, 18, 23, 28 mm 8, 13, 18, 23, 28 mm 2.5 mm2.5 mm

8, 13, 18, 23, 33 mm 8, 13, 18, 23, 33 mm 3.5 mm3.5 mm

Stent Lengths Stent Lengths Stent DiametersStent Diameters

30d 6mo 9mo 12mo 2yr 3yr 4yr 5yr

ZOMAXX II TrialRandomized, Non-inferiority Trial, Clinical Endpoint

ZOMAXX II TrialRandomized, Non-inferiority Trial, Clinical Endpoint

Clinical follow-up

Radiographic follow-up QCA/IVUS

1670 subjects~ 75 sitesUSA and Canada

Primary endpoint: Non-inferiority to TAXUS using 9-mo ischemia driven target vessel revascularization (TVR)

Secondary endpoint: In-segment late loss at 9 mo. (QCA) Additional Analyses: Binary restenosis, MACE, TLR, TVR, in-stent late loss, neointimal volume, clinical

outcomes by vessel diameter and lesion lengthsMedications: Clopidogrel 75 mg QD for 6 months, ASA 325 mg QD for at least 12 months


TriMaxx Stent PatternTriMaxx Stent Pattern8 or 10 cells around perimeter 8 or 10 cells around perimeter 2 connectors between rings 2 connectors between rings

O.C.C.™ (Offset Crown Connector): connecting foot pulls the rings closer together and offsets the apexes of the crowns for improved scaffolding

O.C.C.™ (Offset Crown Connector): connecting foot pulls the rings closer together and offsets the apexes of the crowns for improved scaffolding

DistalDistal

Offset

zomaxx: abbott's drug eluting stent programme · nir 7 cell bard xt crossflex lc wallstent...

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