The Titan-2 (HexaCath) Titanium Nitride Oxide Coated stent:Do Clinical Trial Results Suggest Lower

Restenosis?

Morris Mosseri, MD FESC

Head of Cardiology DivisionMeir Medical Center, Kfar-Sava Israel

I DO NOT have a financial

interest/arrangement or affiliation with the

organization that could be perceived as a

real or apparent conflict of interest in the

context of the subject of this presentation.

Disclosure Statement of Financial Interest

TiNOX

The Titan stent is a balloon expandable stent with

a helical design made of stainless steel and

coated with Titanium-Nitride-Oxide (TiNOX)

Background

It completely prevents

discharge of nickel, chromium

and molybdenum

TiNOX Mechanisms of Action

Minimizes RBC’s damage

Minimizes Fibrin Growth

Inhibits Platelet Aggregation

Titanium-NO LTI Carbon

It reduces inflammationFeng Zhang et al, J of Biomed Mater Res 42: 128-133, 1998

TiNOX Mechanisms of Action

It promotes healing

TITANIUM OXIDES PROMOTE RE-ENDOTHELIALIZATION

Hung-I Yeh et al, J of Biomed Mater Res 76A: 835-841, 2006

TiNOX Mechanisms of Action

Stent Coating With Titanium-Nitride-Oxide for

Reduction of Neointimal Hyperplasia in Pigs

% Intima Reduction

(%)

-60

-40

-20

0TiNOX 1 TiNOX 2

Neointimal Hyperplasia

(mm

2)

0

1

2

3

4

Uncoated TiNOX 1TiNOX 1 TiNOX 2

p<0.02

p<0.02

p=0.8

Windecker S et al. Circulation 2001;104:928-33

Do Clinical Trial Results

Suggest Lower Restenosis?

First Registry: 6 months angiographic results

Randomized Clinical Trial vs. BMS

Real World Data

Registries

Comparative analysis with BMS and DES registries

High risk patients data

Randomized Clinical Trial vs. DES

Comparative registries with BMS and DES

First TiNOX Registry

(for CE approval)

Six months angiographic follow up was

completed in 81 patients

• Late loss 0.54 mm

• Binary angiographic restenosis 14%

Camenzind et al

A Randomized Study Comparing a Titanium-

Nitride-Oxide Coated With an Uncoated Stent

For Coronary Revascularization

Stephan Windecker, Adnan Kastrati,

Bernhard Meier, Otto Hess

Swiss Cardiovascular Center Bern, Switzerland

Circulation 2005

Study DesignRandomized, single-blind, multicenter trial

Study

N=92

Uncoated

X stent

N=47

Coated

X stent

N=45

R

Primary endpoint: Late lumen loss at 6 months

Secondary endpoint: MACE at 30 days and 6 months

Net Luminal Gain

1.55

1.03

0

0.5

1

1.5

2

2.5

Coated

(n=42)

Uncoated

(n=43)

P=0.003

Late Loss

P=0.03

0.55

0.90

0

0,4

0,8

1,2

1,6

Coated

(n=42)

Uncoated

(n=43)

Study – QCA Results at 6 Monthsm

m

mm

0 0

7 7

2 2

2723

0

10

20

30

40

Death MI TLR MACE

Coated Uncoated

%

ns ns

RR 74%

P=0.02

RR 69%

P=0.07

Study – Clinical Results at 6 Months

0

.2

.4

.6

.8

1

0 1 2 3 4 5 6

TL

R

Years

p=0.05

TiNOX

ControlTLR

The TINOX 1-Trial5 year Follow-up

0

.2

.4

.6

.8

1

MA

CE

0 1 2 3 4

Years

p=0.03

TiNOX

Control

5 6

The TINOX 1-Trial5 year Follow-up

MACE

The Titan StentData from the Israeli National Registry

M. MosseriOn Behalf of the Israeli Working Group

on Interventional Cardiology

Real-World Multi-Center (9 hospitals) Registry

To assess the 30 day and 6 month

Outcome of the Titan Stent

Purpose

• High risk patients` clinical profile

• Complex lesion morphology

MACE follow up

180 days (%)30 days (%)Type

00Death

10TVR – PCI

20TVR – CABG

00QWMI

00NQWMI

30Total

Mosseri M et al. Cardiovasc Revasc Med 6(1); 2-6, 2005

Extended Registry of 296 patients

6 months - % (no)30 days - % (no)Type

0.7% (2)0.3% (1)Death

5.7% (17)

(TLR-5.4%)

0.6% (2)TVR *

5.1% (15)0.6% (2)PCI

0.6% (2)0CABG

0.3% (1)0.3% (1)QWMI

0.3% (1)0.3% (1)NQWMI

7.0% (21)1.2% (5)Total MACE

6.3% (19)1.0% (3)

Total Pts with MACE

(hierarchical analysis)

Mosseri et al, EuroIntervention 2: 192-196; 2006

Comparative Results of the TiNOX with BMS and DES

Comparison of TiNOX-1 with SIRTAX 2 Trial

TLR

0

5

10

Cu

mu

lativ

e I

ncid

en

ce

of

TL

R (

%)

0 6 12 18 24Follow-up (months)

Sirolimus eluting stent Paclitaxel eluting stent

Post-SIRTAX Patients

SES:

1.5%

PES:

5.5%

Titanium4.3%

HR=0.57

(0.32-1.01)

P=0.05

SES:

4.1%

PES:

6.9%

SIRTAX 2 TrialMACE

0

5

10

15

20

Cu

mu

lative

In

cid

en

ce

of

MA

CE

(%

)

0 6 12 18 24Follow-up (months)

Sirolimus eluting stent Paclitaxel eluting stent

Post-SIRTAX Patients

HR=0.71

(0.50-0.99)

P=0.04

SES:

12.9%

PES:

17.4%

SES:

7.1%

PES:

11.7%Titanium10.4%

Comparison of TiNOX-1 with SIRTAX 2 Trial

MACE

0.01.02.03.04.05.06.07.08.09.0

10.011.012.013.014.015.0

TVR MACE Death

Isr Bare stents

Isr E-Cypher 6 mts

Isr Titan 6 mts

%

Comparison of the Titan registry with the E-Cypher

and another 17 Israeli BMS registries at 6 months

PORI Registry (FINLAND)

Pasi Karjalainen, MD, PhD

EuroIntervention 2: 187-191; 2006

12 Months MACE Composition

0.5

2.5

4.55

0

10.9

2.5

3.9

10.3

4.9

3.4

13.7

3.34.3

9.2

7.1

1.6

17.9

0

4

8

12

16

20

Cardiac

Death

Overall

Death

AMI TLR ST MACE

TITANOX

PES

BMS

%

p = 0.03

36 Months MACE Composition

1

5.57.5

13.9

3.4

6.4

19.1

23.5

6

8.7

14.7

31.5

0

10

20

30

40

Cardiac Death Overall Death AMI MACE

TITANOX

PES

BMS

%

p < 0.001

p = 0.003

[0.002] [ <0.001 ]

Titan in High Risk Patients

9 HOSPITALS IN SPAIN; 156 PATIENTS; 197 STENTS; 6 MONTHS CLINICAL FOLLOW-UP

THE TIBET REGISTRYM. Valdés, J. Fernández, A. Bethencourt, E. Pérez,

I. Calvo, JR López, A. Martínez, R Valdesuso, J Moreu

DESIGNED TO DEFINETHE CLINICAL EFFICACY

OF TITAN IN DIABETIC PATIENTS

TCT 2004

1/155

155158

156158

4/155

2/155

11155

16155

2/155

DEATH

0.64

2.58

1.29 1.29

7.09

10.3

0

3

6

9

12

CARDIAC NON CARDIAC UNKNOWN QwMI TLR MACE

1/155

4/155

2/155

DEATH

11155

16155

2/155

6 MONTHS FOLLOW-UP

%

RVD mm 3,02

LESION LENGHT mm 18,34

MLD PRE mm 0,81

MLD POST STENT mm 2,55

MLD 9 M FOLLOW-UP mm 1,99

% STENOSIS PRE % 73,22

% STENOSIS POST % 15,5

% STENOSIS 9 MONTHS % 29,67

ACUTE GAIN mm 1,74

LATE LOSS mm 0,56

LATE LOSS INDEX 0,32

9 MONTHS ANGIOGRAPHIC FOLLOW-UP. PATIENTS: 38/45 (84,44). STENTS: 62/72 (83,78%)

7 patients refused repeat angiography. All asymptomatic

31.6

15.55 17.6

5.10

5

10

15

20

25

30

35

BMS TITAN SES TAXUS

BMS TITAN SES TAXUS

16

7.09 7.25.2

0

2

4

6

8

10

12

14

16

18

20

BMS TITAN SES TAXUS

BMS TITAN SES TAXUS% %

ANGIOGRAPHIC RESTENOSIS AND TLR IN DIABETICS

Restenosis TLR

TITAX AMI Trial

A Prospective, Randomized Multi-Center Trial(Findland) Comparing Titanium-Nitride-Oxide-

Coated Stent and Paclitaxel-Eluting Stent

in Acute MI

P Karjalainen,

J. Airaksinen, A. Ylitalo, M. Niemelä, K. Kervinen, M. Pietilä, J. Sia, K. Nyman, P. Tuomainen, T. Mäkikallio

PCR 2007

TITAX AMI trial: Study Design

425 Patients Presenting Acute

Myocardial Infarction Requiring PCI

Written Informed Consent

Randomization 1:1

TITAN® stent (Hexacath)

Titanium-Nitride-Oxide Coated Stent

(TITANOX)

214 Patients

TAXUS-Liberte® stent (Boston)

Paclitaxel-Eluting Stent

(PES)

211 Patients

TITAX AMI trial

• Primary Endpoint

- MACE at 12- months including

• MI

• TLR

• Cardiac death

• Secondary Endpoints

- Composite of cardiac death or recurrent MI

- All cause death

- Stent Thrombosis (ARC definition)

TITAX AMI trialPrimary Endpoint: 12 and 18 months

4.2

9.3

0.5

10.3

8.17.1

1.9

12.8

4.2

9.3

0.5

10.3

11.8

9.5

3.8

17.1

0

5

10

15

20

Myocardial

Infarction

TLR Cardiac

Death

MACE

TITAN 12

TAXUS 12

Column 6

TITAN 18

TAXUS 18

%

p = 0.04

p = 0.02

p = 0.004

12 12 12121818 18 18

TITAX AMI trialSecondary Endpoints: 12 and 18 months

4.2

2.3

0.9

8.5

2.8

4.34.23.3

0.9

13.7

4.7

7.6

0

5

10

15

20

MI or Cardiac

Death

All cause death Stent

Thrombosis*

Titan 12

Taxus 12

Column 6

Titan 18

Taxus 18

%

p = 0.03

p = 0.001

* ARC definition

p = 0.001

1818 1212 12 18

TITAX AMI trialStent Thrombosis: 12 and 18 months

0.50

0.50.9

3.3

0.5 0.5

4.3

0.50

0.50.9

5.2

0.5

1.9

7.6

0

5

10

Definite Probable Possible ARC

definition

Titan 12

Taxus 12

Column 6

Titan 18

Taxus 18

%

p = 0.003

p = 0.03

p = 0.03

p = 0.001

p = 0.04

Do Clinical Trial Results Suggest Lower Restenosis?

• Restenosis rate of the Titan stent is

significantly lower than of BMS (RCT)

• Restenosis rate of the Titan stent in

acute MI patients at 18 months is equal

to PES (RCT)

Conclusions

Do Clinical Trial Results Suggest Lower Restenosis?

• Safety of the Titan stent is better than

PES in terms of stent thrombosis and

long term incidence of MI and cardiac

death both in acute MI (RCT) and the

general population (PORI registry).

Conclusions