The document describes several clinical studies that evaluated the outcomes of using titanium-nitride-oxide coated stents in patients undergoing percutaneous coronary intervention (PCI). A randomized trial found that the coated stents significantly reduced late lumen loss and restenosis at 6 months compared to uncoated stents. A large registry of over 500 patients treated with the coated stents found low rates of major adverse cardiac events, target lesion revascularization, and stent thrombosis up to 1 year. The studies suggest the coated stents provide effective treatment with only short-term dual antiplatelet therapy, but direct comparison to drug-eluting stents is still needed.

2. Stent Coating With Titanium-Nitride-Oxide for Reduction of Neointimal Hyperplasia in Pigs Windecker S et al. Circulation 2001;104:928-33

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

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

6. Use of DES 2005 2007

8. 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%

9. Titan Registry – Clinical Presentation 33% 26% STEMI NSTEMI/UA 50% Left ventricular ejection fraction (%) 56% Multivessel disease 59% Acute coronary syndrome 41% Chronic stable angina Titanium N=507

10. Titan Registry – Procedural Characteristics Titanium N= 507 Number of lesions per patient 1.5  0.5 Number of stents per lesion 1.2  0.4 Stent diameter (mm) 2.9  0.5 Stent length per lesion (mm) 23  12

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

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

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

14. One Year Clinical Outcome %

15. MACE and TLR Diabetic vs Non-Diabetic Patients % P=0.06 P<0.001

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 Registry Major Adverse Cardiac Events HR=0.71 (0.50-0.99) P=0.04 SES: 12.9% PES: 17.4% SES: 7.1% PES: 11.7% Titanium: 10.4%

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

20. Titan Registry 0 1 2 3 4 Time since PCI in years 0 1 2 3 4 5 Cumulative incidence, % Incidence density 1.0 / 100 pt years 3.3% 3.5 0.6% / year 192 definite ST cases Bern-Rotterdam Cohort Study of Drug-Eluting Stents Daemen J et al. Lancet 2007;369:667-78

22. Symptomatic Coronary Artery Disease Exclusion: Acute STEMI Vessel Diameters: ≥ 2.25 – ≤ 4.0 mm Stent Diameters: 2.25 – 4.0 mm Stent Lengths: 8 - 28 mm Pre-Dilatation and Post-Dilatation @ Physicians Discretion 30 d 6 mo 8 mo 12 mo 2 -5 yrs Clinical Follow-Up Primary Endpoint: In-Stent Late Loss at 8 months Key Secondary Endpoints: MACE at 30 days, 6 months, 12 months Clinically driven TLR, TVR, & TVF at 6 and 12 months Device, Lesion and Procedure Success Anti-Platelet Therapy for a minimum of 3 months ENDEAVOR n= ~150 Sites: Switzerland (3) Randomized (1:1), Single-Blind, Multi-Center Study TiNOX n= ~150 Titanium-Nitride-Oxide Coated Stents vs. Endeavor Stent

23. One Year Clinical Outcome %