This document summarizes the results of a multi-center registry assessing the short and long term outcomes of using the Titan stent in 296 patients. Some key findings include: - At 6 months follow-up, the rates of target vessel failure and major adverse cardiac events were 10.9% and 12.1% respectively. - The rates of target lesion revascularization at 30 days and 6 months were 0.6% and 5.7% respectively. - The Titan stent demonstrated a good safety profile with no deaths within 30 days and a cardiac death rate of 1% at 6 months. - The results compare favorably to other stent registries conducted in Israel.

1. Morris Mosseri, MD Director of Interventional Cardiology Hadassah-Hebrew University Medical Center The Israeli Working Group of Interventional Cardiology The Titan Stent in Real Life Results from a Multi-Center Registry

2. Stainless steel and Cobalt-Chromium stents contain considerable amounts of Nickel , Chromium and Molybdenum : Nickel Chromium Molybdenum 316L SS 12-15% 17-19% 2-3% Co-CR Vision 9-11% 19-21% ___ Co-Cr Driver 33-37% 19-21% 9-10% Background

3. Allergy 5-15 % of the population are allergic to Nickel. Nickel allergy Background

4. All patients with positive allergic patch-test reactions had a restenosis at 6 months post stenting. Koster R et al Lancet 2000:356; 1895-7. Nickel and Molybdenum contact allergies in patients with coronary in-stent restenosis. P=0.03 131 42 89 121 42 79 Negative patch test 10 0 10 Positive patch test Restenosis (-) Restenosis (+)

5. The Inflammatory Equilibrium Inflammatory factors Systemic (vulnerable patient) Local (vulnerable plaque) Procedural (trauma) Stent (“foreign” material) Anti-inflammatory therapy DES Systemic therapy

6. TiNOX The Titan stent (Hexacath, France) is a balloon expandable stent made of stainless steel and coated with Titanium-Nitride-Oxide (TiNOX) which completely prevents discharge of nickel, chromium and molybdenum . Background

7. Purpose To assess the short and long term characteristics of the Titan stent in a multi-center registry.

8. The Titan Israeli Registry (296 patients) List of centers and investigators: Hadassah - Mosseri M. Ichilov - Miller H. Barzilai - Jefferey J. Hillel-Jaffe - Friemerman A. Naharia - Brizines M, Poriah - Hasin Y. Shiba - Guetta V Wolfson - Tamari I. Ziv - Plich M, ISRAEL

9. Methods Inclusion criteria This real life registry included all patients candidate for stent implantation. Choosing of Titan stent was at the operator discretion. Exclusion criterion Cardiogenic shock

10. Methods Lesions : De novo and restenotic lesions of native coronary arteries and SVG’s.

11. 30 day and 6 months follow-up was performed by an independent research nurse. Methods

12. Outcome data included immediate technical and clinical success and complications, and MACE (sub-acute thrombosis, MI, TLR and death) at 30 days and 6 months. Methods

13. Demographics Patients - 296 Age 68.8±11.8 (33-87) Lesions - 333 Results %

14. Risk factors %

15. Cardiac history prior to PCI %

16. Indications for PCI %

17. Distribution of patients per number of narrowed coronary arteries

18. Blood vessels treated

19. Lesion location

20. Lesion type

21. Lesion characteristics Length <15 mm Length 15-20 mm Length >20 mm

22. Indications for stenting % Acute MI Prevention of restenosis >30% Residual stenosis In-stent restenosis Dissection

23. Stent diameter (mm)

24. Stent Length (mm) Number of stents

25. Delivery Data % %

26. Delivery data 0 0 No Flow 0 0 Distal dissection 0 0 Proximal dissection 0.6 2/296 Balloon rupture 0.3 1/296 Unsuccessful delivery % No Type

27. Early Complications 0 0 Death 0 0 CABG 0 0 Side branch acute occlusion 0.6 2/296 Sub-acute stent thrombosis 0 0 Acute occlusion / Q wave MI % No Type

28. Adverse Events at 12 months Another 39 patients who underwent coronary angiography during follow up had patent Titan stent. 10.9% (32) Total pts with TVF 10.9% (32) Total pts with MACE 12.1% (36) TVF - Target Vessel Failure (Cardiac death, MI, TVR) 12.5% (37) MACE (Death, MI, TLR) 0.3% (1) NQWMI 0.3% (1) QWMI 9.6% (28) / 1% (3) PCI / CABG 10.6% (31) TVR 9.6% (28) / 0.6% (2) PCI / CABG 10.1% (30) TLR 1.7% (5) 1% (3) 0.7% (2) Death Cardiac Non-cardiac 12 months - % (no) Type

29. MACE at 30 days and 6 months follow up * Another 24 patients who underwent coronary angiography during follow up had patent Titan stent. 6.3 (19) 1.0 (3) Total Patients with MACE 7.0 (21) 1.2 (5) Total MACE 0.3 (1) 0.3 (1) NQWMI 0.3 (1) 0.3 (1) QWMI 0.6 (2) 0 CABG 5.1 (15) 0.6 (2) PCI 5.7 (17) 0.6 (2) TVR (=TLR)* 0.7 (2) 0.3 (1) Death 6 months - % (no) 30 days - % (no) Type

30. MACE at 30 days and 6 months follow up See notes page for report on the 2 patients who died

31. Functional class at 6 months 1 Class IV 1 Class III 15 Class II 83 Class I 6 months (%) Type

32. Results of 17 stent registries in Israel 6 months follow-up %

33. Discussion TLR rate in randomized trials tends to be higher than registries because patients may undergo follow-up angiographic driven revascularization. Therefore, comparison of studies of the same kind (registries, randomized studies) is preferable.

34. Discussion Restenosis reaches plateau at different terms: 6 months after BMS, 9-12 months after DES implantation. Therefore, it is more appropriate to compare restenosis rate, MACE and TLR of various stents at their plateau of restenosis rather than after fixed period of time.

35. Discussion Since death is an ultimate and irreversible complication, its clinical importance exceeds that of other MACE such as TLR and hospital admissions.

36. Discussion In the Israeli registries Cypher’s MACE and TLR rates were slightly lower than Titan’s whereas death rate was somewhat higher, possibly due to sub-acute and late thrombosis

37. The Titan stent has a remarkable safety profile and can be used in complex coronary lesions Conclusions

38. After adjusting for the significance of different MACE, current studies suggest that Titan is clinically comparable to DES Conclusions

39. Thank you !