TITAX AMI Trial

Y. Giraud-Sauveur on behalf of

P.Karjalainen, MD, PhD : Principal Investigator

BCIS 2009 London, UK

A Prospective, Randomized Trial Comparing TITAN-2® Stent and TAXUS-Liberte® Stent in

Acute Myocardial Infarction

24-months Clinical Follow-Up

TITAX AMI trial

P Karjalainen, MD, PhDJuhani Airaksinen, Antti Ylitalo, Matti Niemelä,

Kari Kervinen, Mikko Pietilä, Jussi Sia,

Kai Nyman, Petri Tuomainen, Timo Mäkikallio

for the TITAX AMI Investigators

All investigators state that no relationships

exist related to this presentation

Titanium-NO Mechanisms of Action

Inhibits Platelet Aggregation

Minimizes Fibrin Growth

Reduces Inflammation

Promotes Healing

Multifunctional Anti-restenotic EffectMultifunctional Anti-restenotic Effect

- Stabilizes microtubules to inhibit smooth muscle cell migration and proliferation

- Stable and durable Translute Polymer * Vascular compatible, biocompatible * Controlled and consistent dose release of paclitaxel

Background: TITAX AMI at 1-YearEurointerv 2008;4:234-241

TCT 2007, Late Breaking Trial

Comparison of titanium-nitride-oxide-coated Comparison of titanium-nitride-oxide-coated TITAN-2TITAN-2®®

Stent to the paclitaxel-eluting Stent to the paclitaxel-eluting TAXUS-LiberteTAXUS-Liberte®® stent stent

resulted in:resulted in:

• Comparable clinical outcome at 1-Year

• Secondly, although the overall risk of stent thrombosis although the overall risk of stent thrombosis was low, it concentrated on the use of TAXUS-Libertewas low, it concentrated on the use of TAXUS-Liberte®® stentstent

• In addition, stent thrombosis occurred in 3 patients after premature discontinuation of clopidogrel.

Participating Centers in Finland

Purpose ofthe TITAX AMI trial

Initiated by the investigators

A Prospective, Multi-center, Randomized Trial that

Compares the Implantation of Titanium-Nitride-Oxide

Coated Stents to Paclitaxel-Eluting Stents for Acute

Myocardial Infarction

Finland

Sweden Russia

* Pori

* * Turku

* Oulu

* Kokkola * Kuopio

* Jyväskylä

Norway

Estonia

Inclusion Criteria:

•• Written informed consent

• Age > 18 years

• Patient with symptoms and

signs of myocardial

infarction requiring PCI

Exclusion Criteria:

•• Prior PCI on target vessel

(restenosis)

• Unprotected LM disease

• Ostial lesion

• Contraindication to aspirin,

heparins, clopidogrel,

(allergy / risk for bleeding)

• Life expectancy < 12 months

• Stent length needed > 28 mm

Inclusion / Exclusion

TITAX AMI trial: Study Design425 Patients Presenting Acute

Myocardial Infarction Requiring PCI

Written Informed Consent

Randomization 1:1

TITAN-2® stent (Hexacath)Titanium-Nitride-Oxide Coated StentTitanium-Nitride-Oxide Coated Stent

(TITANOX)(TITANOX) 214 Patients

TAXUS-Liberte® stent (Boston)Paclitaxel-Eluting Stent

(PES) 211 Patients

Primary Endpoint: MACE at 1 Year

Independent Endpoint CommitteeIndependent Endpoint Committee

TITAX AMI trial

•• Primary Endpoint

MACE at 12- months including• Myocardial infarction• TLR (PCI or CABG)• Cardiac death

•• Secondary Endpoints

- Composite of cardiac death or recurrent MI - All cause death - Stent Thrombosis

Definition of Stent Thrombosis The Academic Research Consortium (ARC)

Definite: - Acute coronary syndrome and angiographic (or autopsy) confirmation of stent thrombosis

Probable:- Any unexplained death within the first 30 days- Target vessel related AMI

Possible:- Any unexplained death from 30 days after PCI

Baseline Patient Characteristics TITAN-2®

(N=214)

TAXUS-L*®

(N=211)

P value

Age (mean ± SD) 64 ± 11 64 ± 11 0.72

Male sex, n (%) 162 (76) 157 (74) 0.82

Diabetes, n (%) 48 (22) 33 (16) 0.08

History of smoking, n (%) 113 (53) 97 (46) 0.18

Hyperlipidemia, n (%) 141 (66) 151 (72) 0.21

Previous PCI, n (%) 22 (10) 10 (5) 0.04

Previous CABG, n (%) 16 (7) 13 (6) 0.70

Acute STEMI, n (%) 83 (39) 97 (46) 0.14

Thrombolysis, n (%) 26 (12) 40 (19) 0.06

GP IIb/IIIa Inhibitors, n (%) 116 (54) 96 (45) 0.81

* L= Liberte* L= Liberte

Lesion Characteristics TITAN-2®

(N=214)

TAXUS-L*®

(N=211)

P value

Infarct-related Vessel, n (%)

LAD 98 (46) 91 (43) 0.63

LCX 44 (21) 50 (24) 0.48

RCA 62 (29) 60 (28) 0.92

Left Main 0 (0) 1 (0.5) 0.50

Bypass Graft (venous) 10 (5) 9 (4) 0.84

Complex Lesions, n (%)

B1 / B2 147 (69) 138 (65) 0.54

C 35 (16) 24 (11) 0.16

* L= Liberte* L= Liberte

Procedural and Lesion Characteristics TITAN-2®

(N=214)

TAXUS-L*®

(N=211)

P Value

RVD, (mm) 3.16 ± 0.45 3.11 ± 0.50 0.35

Lesion length, (mm) 13.6 ± 5.6 13.2 ± 6.4 0.47

Stent diameter, (mm) 3.16 ± 0.42 3.11 ± 0.45 0.19

Stent length, (mm) 17.4 ± 4.5 17.7 ± 5.3 0.48

Total stent length, (mm) 18.5 ± 6.4 19.2 ± 7.2 0.26

No of stents per lesion, n (%) 1.1 ± 0.3 1.1 ± 0.4 0.24

Acute Procedural Success, n (%) 213 (99.5) 207 (98.1) 0.21

Multivessel PCI, n (%) 30 (14) 19 (9) 0.13

* L= Liberte* L= Liberte

Antiplatelet Agent Utilization

TITAN-2®

(N=214)

TAXUS-L*®

(N=211)

P

value

Aspirin

- At 6 months 100% 98.6% ns

- At 12 months 100% 98.6% ns

Clopidogrel

- At 6 months 89.3% 98.1% < 0.05

- At 12 months 31.3% 65.4% < 0.001

Mean duration, (months) 7.6 10.1 < 0.001

* L= Liberte* L= Liberte

Extended clopidogrel treatmentsExtended clopidogrel treatmentsbeyond 12 months were discouragedbeyond 12 months were discouraged

Patient Flow - ClinicalRandomized

(N=425)

TITAN-2® stent(N=214/214)

TAXUS-Liberte® stent (N=211/211)

1-Year follow-up1-Year follow-up(N=425/425; 100%)(N=425/425; 100%)

TITAN-2® stent(N=214/214)

24 months follow-up24 months follow-up(N=424/425; 99.8%)(N=424/425; 99.8%)

TAXUS-Liberte® stent (N=210/211)

1 = Lost to f/u1 = Lost to f/uLost to f/u = 0Lost to f/u = 0

TITAX AMI trialMACE at 12, 18 and 24 months

10,3

12,8

000

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

p = 0.5

TITAX AMI trialMACE at 12, 18 and 24 months

10,3

12,8

17,1

10,3

0

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

p = 0.04

p = 0.5

TITAX AMI trialMACE at 12, 18 and 24 months

10,311,2

12,8

17,1

21,3

10,3

0

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

p = 0.04

p = 0.5

p = 0.006

TITAX AMI trialMI at 12, 18 and 24 months

4,25,1

8,1

11,8

15,6

4,2

0

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

p = 0.004

NS

p < 0.001

TITAX AMI trialCardiac Death at 12, 18 and 24 months

0,5 0,91,9

3,84,7

0,5

0

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

p = 0.02

NS

p = 0.02

TITAX AMI trialTLR at 12, 18 and 24 months

9,3 9,3

7,1

9,5 109,3

0

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

NSNSNS

TITAX AMI trialDefinite Stent Thrombosis at

12, 18 and 24 months

0,5 0,5

3,3

5,2 5,7

0,5

0

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

p = 0.003

p = 0.03

p = 0.001

TITAX AMI trialMI or Cardiac Death at 12, 18 and 24

months

4,25,1

8,5

13,7

18,5

4,2

0

5

10

15

20

25

12 18 24

TITAN-2

TAXUS-Liberte

%

p = 0.001

p = 0.08

p < 0.001

TITAX AMI trial:Conclusions (24 months follow-up)

• Late follow up (12 to 24 months) after the clopidogrel discontinuation showed higher rates of:- Myocardial Infarction- Cardiac Death- MACE

with the use of TAXUS-Liberte® stent

• Secondly, the incidence of Stent Thrombosis (ARC definition) was significantly higher in the TAXUS-Liberte® stent group

• TITAN-2® stent: non-inferior 24-months rate of TLR

TITAX AMI trial

Possible limitations:Possible limitations:

• Small sample size (425 patients)

• Thrombolysis therapy not excluded

Strengths of the study:

• Initiated by the investigators, no sponsors

• Prospective, randomized, multicenter study

• Primary clinical end point

• New ARC definition of stent thrombosis

TITAX AMI trial

P Karjalainen, MD, PhDJuhani Airaksinen, Antti Ylitalo, Matti Niemelä,

Kari Kervinen, Mikko Pietilä, Jussi Sia,

Kai Nyman, Petri Tuomainen, Timo Mäkikallio

for the TITAX AMI Investigators

Thank You!

Kiitos!