1. FMRP 2014 | 1 Marc Bosiers Koen Deloose Joren Callaert A.Z. Sint-Blasius, Dendermonde Imelda Hospital, Bonheiden Patrick Peeters Jürgen Verbist OLV Hospital, Aalst Lieven Maene R.Z. Heilig Hart, Tienen Koen Keirse Bart Joos BEC 2014, София Koen Deloose, MD Preliminary 6-months Results of the DESTINY 2 trial

2. FMRP 2014 | Level 1 evidence in the coronaries… 2 Stettler C. et al (2007). Lancet, 370(9591), 937-948.Roiroin C. et al (2006). Heart, 92, 941-949.

3. FMRP 2014 | Transfer the enthousiasm to the BTK…??? 3 Tibial vessels ?

4. FMRP 2014 | Randomized trials for DES-BTK 4 Achilles  Sirolimus eluting (Cypher) stent vs. POBA Yukon  Sirolimus eluting (Yukon/no polymer) stent vs. BMS Destiny  Everolimus eluting stent (Xience) vs. BMS (Multilink Vision)

5. FMRP 2014 | YUKON, DESTINY & ACHILLES trials (n=515) overview of 1-year Primary Patency 5 Rastan A. et al (2011). European Heart Journal, 32, 2274-2281 Bosiers M. et al (2012). Journal of Vascular Surgery, 55, 390-398 Scheinert D. et al (2012). Journal of the American College of Cardiology, 60, 2290-2295

6. FMRP 2014 | overview 6 Biondi-Zoccai G. et al (2009). Journal of Endovascular Therapy, 16(3), 251-260. Primary Patency 100 90 80 70 60 50 40 30 20 10 0 0 5 10 15 20 25 30 35 40 45 50 55 60 Time (months) DES-registry BMS-registry Linear (DES-Registry) Linear (BMS-Registry) DES-RCT BMS-RCT

7. FMRP 2014 | Excellent results… 7

8. FMRP 2014 | …but for very small lesion lengths 8 Average lesion length: 15.9mm

9. FMRP 2014 | …not according to daily reality… Real world = Longer lesions 9

10. FMRP 2014 | 10 Long term vessel patency is limited by patency rate of segment treated with PTA only PTA only DES Follow-up Procedure Drug eluting stents: treatment effect Real world = Longer lesions

11. FMRP 2014 | 11 Coronary DES trials showed –Inadequate lesion coverage may contribute to edge stenosis  Increased risk for restenosis if full index lesion is not completely covered by DES Sakurai et al. Am J Cardiol 2005;96:1251–1253. Real world = Longer lesions

12. FMRP 2014 | DESTINY 2 study Prospective, non-randomized, multi-center study To evaluate the immediate and long-term (up to 12 months) outcome of the XIENCE PRIME Everolimus-Eluting Coronary Stent System (Abbott Vascular) in 30 – 100 mm lesions

13. FMRP 2014 | DESTINY 2 study Device description XIENCE PRIME Everolimus-Eluting Coronary Stent System (Abbott Vascular) Balloon-expandable stent Everolimus-eluting

14. FMRP 2014 | DESTINY 2 study Participating centers BELGIUM –M. Bosiers, K. Deloose, J. Callaert - AZ Sint-Blasius, Dendermonde –P. Peeters, J. Verbist - Imelda Hospital, Bonheiden –L. Maene, R. Beelen - OLV, Aalst –K. Keirse - RZ Heilig Hart, Tienen GERMANY –D. Scheinert - Herzzentrum Leipzig –T. Zeller - Herz-zentrum Bad Krozingen –G. Torsello - St Franziskus Hospital, Münster AUSTRALIA –R. Varcoe - Prince of Wales Private Hospital, Sydney 60 patients

15. FMRP 2014 | DESTINY 2 study Study design Main inclusion criteria Rutherford classification 4 & 5 De novo lesion in the infrapopliteal arteries Total target lesion length : 30mm - 100mm Primary endpoint Primary patency at 12 months, defined as: absence of restenosis (≥50% stenosis) or occlusion within the originally treated lesion based on angiography, verified by Core Lab.

16. FMRP 2014 | DESTINY 2 study Timeline 1 M 6 M12 Mproc Medication Physical examination Rutherford ABI Core Lab Angiography Core Lab Ultrasound Core Lab X-ray disch To date: Preliminary 6 months results of 1st 30 patients available

17. FMRP 2014 | DESTINY 2 study: Patient demographics N=30 Male (%) 22 (73.3%) Age (min – max; ±SD) 74 (48 – 91; ±11.76) Nicotine abuse (%) 8 (26.7%) Hypertension (%) 20 (66.7%) Diabetes mellitus (%) 17 (56.7%) Renal insufficiency (%) 11 (36.7%) Hypercholesterolemia (%) 14 (46.7%) Obesity (%) 11 (36.7%) Rutherford 4 (%) 14 (46.7%) Rutherford 5 (%) 15 (50.0%)

18. FMRP 2014 | DESTINY 2 study: Lesion characteristics N=30 Left/Right limb (%) 14 (46.7%) / 16 (53.3%) Lesion length 48.6 mm Reference vessel diameter 3.1 mm Mean lumen diameter 0.3 mm Occlusion (%) 11 (36.7%) Calcified lesion (%) 12 (40.0%)

19. FMRP 2014 | DESTINY 2 study: 6 Month Survival – 1 st 30 patients timebaseline1MFU 6MFU at risk3028 21 %100 95.0 95.0 %

20. FMRP 2014 | DESTINY 2 study: 6 Month Primary Patency – 1 st 30 patients timebaseline1MFU 6MFU at risk3027 20 %10093.2 93.2 %

21. FMRP 2014 | DESTINY 2 study: 6 Month Freedom from TLR – 1 st 30 patients timebaseline1MFU 6MFU at risk3028 20 %10096.7 92.6 92.6 %

22. FMRP 2014 | DESTINY 2 study: 6 Month Limb salvage – 1 st 30 patients timebaseline1MFU 6MFU at risk3028 21 %10096.7 96.7 %

23. FMRP 2014 | Example case: screening 48 year old male Risk factors: –Previous coronary and cerebrovascular interventions Clinics: –Restpain right leg –Rutherford 4, ABI: 0.55 –Duplex US: Biphasic signals distally 23

24. FMRP 2014 | Example case: baseline procedure 24

25. FMRP 2014 | 25 Example case: baseline procedure Xience Prime 3.5 x 38 mm Xience Prime 3.5 x 33 mm Xience Prime 3.5 x 15 mm

26. FMRP 2014 | 26 Example case: 12M follow-up No complaints Rutherford 0, ABI: 0.89 Stenosis at 12M: 5%

27. FMRP 2014 | 27 Example case: 12M follow-up No stent fractures RAO 25 RAO 8 LAO 16

28. FMRP 2014 | Conclusion We already knew that drug eluting stents work in focal BTK lesions Destiny 2 shows in an preliminary way that also longer BTK lesions up to 10 cm can successfully be treated with everolimus DES