TITAN STENT titanium nitride oxide coated stent

1. TITAN STENTtitanium nitride oxide coated stent • F.FUNCK .M.D. • PONTOISE HOSPITAL /PARIS UNIVERSITY • FRANCE

2. WHICH STENT FOR WHICH PATIENT ? • REGARDING THE RATE OF RESTENOSIS WITH BMS, SOME CARDIOLOGISTS WERE LOOKING FORWARD TO USE DRUG ELUTING STENT (DES ) • IN EUROPE ,THE RATE OF USE OF DES IS DEPENDING ON THE COUNTRY (BETWEEN 40 AND 70 % ) • INTERNATIONAL DEBATE (ESC 2006 ) AROUND THE RISK OF DES ( ACUTE THROMBOSIS, LATE THROMBOSIS ,..) • EUROPEAN GUIDELINES TO CONTINUE ANTIPLATELET TREATMENT 1 YEAR; • BLEEDING RISK OF THIS KIND OF TREATMENT (ESP. IF GENERAL SURGERY IS SCHEDULED OR HIGH RIK PATIENT )

3. WHICH STENT FOR WHICH PATIENT ? • MORE THROMBOSIS WITH DES ? • META ANALYSIS OF INTERNATIONAL STUDIES GIVE DIFFERENT RESULTS BUT • MORE COMPLICATIONS IF DES ARE USED FOR « OFF LABEL » INDICATIONS • ON LABEL INDICATIONS ARE IN EUROPE ( PROXIMAL LAD, DIABETIS PATIENT ,SMALL VESSELS , RESTENOSIS INTRASTENT ,.. )

4. IS THERE AN ALTERNATIVE SOLUTION OF USE OF DRUG ELUTING STENT ? …….

5. -TINOX STUDY-TITAN REGISTRY-COMPARISON TITAN REGISTRY AND SIRTAX II-TITAX AMI TRIAL-PORI STUDY

6. Stent Coating With Titanium-Nitride-Oxide for Reduction of Neointimal Hyperplasiain PigsWindecker S et al. Circulation 2001;104:928-33

7. TiNOX Study DesignRandomized, single-blind, multicenter trialWindecker S et al. Circulation 2005;111:2617-22 Uncoated OMEGA™ stent N=47 TiNOX Study N=92 R TiNOX coated OMEGA™ stent N=45 Angiographic endpoint: In-stent late lumen loss at 6 months Clinical endpoint: MACE at 30 days and 6 months

8. RR 65% P=0.01 TiNOX Study – QCA Results at 6 Months Windecker S et al. Circulation 2005;111:2617-22 Late Loss Binary Restenosis P=0.004 % mm

9. RR 65% P=0.02 RR 70% P=0.006 TiNOX Study - MACE at 6 Months Windecker S et al. Circulation 2005;111:2617-22 ns ns %

10. Use of DES 2005 2007

11. Titan Registry – Patient Demographics Titanium N=507 Mean age (years) 67  12 Male gender 78% Cardiovascular risk factors Arterial hypertension 54% Diabetes mellitus 23% Hypercholesterolemia 47% Family history 24% Smoking 46% Previous MI 13% Previous PCI 12% Previous CABG 9%

12. Titan RegistryMACE (Composite of Death, MI, or TVR) 1 89.6 % .9 cum. event free survival .8 .7 .6 0 100 200 300 Time (days)

13. Titan RegistryTLR 1 95.7 % .95 .9 cum. event free survival .85 .8 0 100 200 300 Time (days)

14. Titan RegistryStent Thrombosis 99.2 % 1 .98 .96 cum. event free survival .94 .92 .9 0 100 200 300 Time (days)

15. One Year Clinical Outcome %

16. SIRTAX II and Titan Registry Patient Demographics Titan Sirolimus Paclitaxel Stent Eluting Stent Eluting Stent p N=507 N=467 N=437 Mean age (years) 67  12 63  12 65 11 <0.001 Male gender 78% 74% 76% NS Cardiovascular risk factors Arterial hypertension 54% 57% 61% NS Diabetes mellitus 23% 23% 23% NS Hypercholesterolemia 47% 52% 52% NS Family history 24% 29% 28% NS Smoking 46% 38% 32% <0.01 Previous MI 13% 13% 13% NS Previous PCI 12% 14% 15% NS Previous CABG 9% 8% 9% NS

17. Procedural Characteristics Titanium Sirolimus Paclitaxel P Eluting Stent Eluting Stent Lesions N= 760 N= 643 N= 603 Number of lesions per patient 1.50.5 1.40.6 1.40.6 NS Number of stents per lesion 1.20.4 1.20.5 1.20.5 NS Stent diameter (mm) 2.90.5 2.80.4 2.90.4 NS Stent length per lesion (mm) 2312 2312 2211 NS Antithrombotic Treatment Titanium Sirolimus Paclitaxel Eluting Stent Eluting Stent Clopidogrel 1 month 12 months 12 months Acetylsalicylic acid indefinitely indefinitely indefinitely

18. SIRTAX II and Titan RegistryMajor Adverse Cardiac Events PES: 17.4% PES: 11.7% SES: 12.9% Titanium: 10.4% HR=0.71 (0.50-0.99) P=0.04 SES: 7.1%

19. SIRTAX II and Titan RegistryTarget Lesion Revascularization PES: 6.9% PES: 5.5% SES: 4.1% Titanium: 4.3% HR=0.57 (0.32-1.01) P=0.05 SES: 1.5%

20. One Year Clinical Outcome %

21. Titan Registry - Conclusions • Titanium-Nitride-Oxide coated stents are safe and effective in complex patients enrolled in routine clinical practice • As opposed to drug-eluting stents, Titanium-Nitride-Oxide coated stents require only short-term dual antiplatelet therapy • Rates of TLR and MACE of Titanium-Nitride-Oxide coated stents are low and deserve further evaluation in direct head-to-head comparison with drug-eluting stents

22. 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 Purpose of the 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

23. TITAX AMI trial: Study Design 425Patients 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 Primary Endpoint: MACE at 1 Year Secondary Endpoints :- Composite of cardiac death or recurrent MI - Stent Thrombosis Independent Endpoint Committee

24. Baseline Patient Characteristics

25. 30-days Follow-up

26. 6-months Follow-up

27. 12-months FU: Secondary Endpoints % p = 0.08 p = 0.031 p = 0.8

28. TITAX AMI trial: Conclusions •Both TITANOX coated stent and PES resulted in comparable clinical outcome. • Secondly, although the overall risk of stent thrombosis was low, it concentrated on the use of PES. • Stent thrombosis occurred in 3 patients after premature discontinuation of clopidogrel.

29. Bio Active Stent in Finland First Treated Patient in PORI May 2003 TITAX AMI trial EuroPCR2007 Late Breaking Trials TCT2007 Helistent® Hexacath, Fra  2002 TITAX AMI Nov 2005- Nov 2006 Karjalainen P, et al. J Invasive Cardiol 2006;18:462-468 PORI stent registry May 2003 – Nov 2004 Titan® Stent in Finland August 2002 Pori Stent Registry Eurointerv. 2006 J Invasive Cardiol. 2006 TCT2005, TCT2006

30. Compare clinical outcome of a stainless steel Stent coated with titanium nitride oxide (TITANOX), paclitaxel eluting stent (PES) and bare metal stent (BMS) in routine clinical practice 3 Years Follow up of the PORI Stent Registries PURPOSE OF THE STUDY Between May 2003 and November 2004, all consecutive patients scheduled for stent implantation were considered for these registries

31. Baseline Clinical Characteristics * p < 0.05

32. Baseline Clinical Characteristics * p < 0.05

33. Procedural and Lesion Characteristics * TITANOX vs. PES / BMS, p < 0.05

34. 30 Days MACE Composition % p = 0.004 p = 0.02 p = 0.02 p = 0.04

35. Late Follow up: End points > 12 months

36. Cumulative Rate of EventsOctober 2007: FU 36 – 52 months

37. • The 519 patients (TITANOX 184, PES 183, BMS 152) who were MACE free at the time of the discontinuation of clopidogrel treatment were followed for an additional 12 months after discontinuation. • The goal was to evaluate late thrombotic events related to clopidogrel discontinuation. Late Follow up in the Year Following Clopidogrel Discontinuation

38. Late Follow up in the Year Following Clopidogrel Discontinuation % All Death / Cardiac death p = 0.007 Stent Thrombosis, p = 0.007 MACE, p = 0.10

39. PORI Stent RegistriesConclusions • Lower rates of recurrent MI and MACE with the use of TITANOX coated stent compared with PES or BMS • Secondly, very low TLR rate with the use of TITANOX coated stent (5.5 %) • PES higher rates of MI and Stent Thrombosis after the discontinuation of clopidogrel compared with TITANOX coated stent or BMS