1. Infrapopliteal Sirolimus-Eluting Versus Bare Metal Stents for Critical Limb Ischemia: Long-Term Angiographic and Clinical Outcome in >100 Patients Dimitris Karnabatidis, MD Ass. Prof. of Interventional Radiology Department of Diagnostic and Interventional Radiology Patras University Hospital, Rion, Greece Head: Prof. Dimitris Siablis

2. Critical Limb Ischemia (CLI) CLI: “chronic ischemic rest pain requiring regular analgesia or non-healing ulcers, or gangrene attributable to objectively proven arterial occlusive disease” Estimated incidence = 400-1000/1,000,000 population per annum ≈ 45% cardiovascular disease mortality rate at 5 years Up to 25% amputation rate despite revascularization attempts Recommendation 73 (TASC SVS 2000) Dormandy JA et al, Saunders, 1998:11-26 Soder HK et al, J Vasc Interv Radiol 2000;11:1021-1031

3. CLI Epidemic  Costs $10-20 billion/year in the US  220000-240000 amputations/year in the US - EU  Someone, somewhere loses a leg due to DIABETES every 30 sec www.cxvascular.com

4. www.ILEGX.com Leg Amputations

5. Surgical Options To date, surgical bypass has been the mainstream therapy for infrapopliteal occlusive disease CLI patients are high-risk surgical candidates with multiple co-morbidities (diabetes mellitus, coronary disease, ischemic nephropathy e.t.c.) 30-50% of CLI patients are not suitable candidates for bypass surgery Peri-operative mortality rate between 1.8 to 6% Siablis D et al. J Endovasc Ther 2005Tsetis D et al, Br J Radiol 2004

6. Interventional Radiology  Low-profile interventional instruments  Expanding worldwide endovascular experience  Reduced peri-interventional morbidity and mortality rates  Shorter procedural time periods  Does not preclude surgical options  First-line therapy of critical leg ischemia Siablis D et al. J Endovasc Ther 2005Tsetis D et al, Br J Radiol 2004 Soder HK et al, J Vasc Interv Radiol 2000Kandarpa K et al, J Vasc Interv Radiol 2001

7.  Suboptimal angioplasty outcome is a well recognized adverse predictor of vessel patency  Balloon angioplasty & bare metal stents: almost equivalent results in the BTK arena  Re-obstruction rate of 41-66% at 1 year according to prospective angiographic studies  Vigorous clinical surveillance is required and frequent re-do procedures Endovascular points Siablis D et al. J Endovasc Ther 2007Feiring AJ et al. JACC 2004 Rand T et al. Cardiovasc Interv Radiol 2006

8. Sirolimus-eluting stents 2 controlled trials and 2 cohort studies Significant inhibition of in-stent restenosis Significant reduction of re-do angioplasty procedures Drug-eluting Stents: BTK Evidence Bosiers M, et al. J Cardiovasc Surg (Torino) 2006 Commeau P, et al. Catheter Cardiovasc Interv 2006 Siablis D, et al. J Endovasc Ther 2007 Siablis D, et al. J Endovasc Ther 2005 Scheinert D, et al. Eurointervention 2006

9. Interim published results

10. Siablis D, Karnabatidis D, Katsanos K, et al. Under peer review 2008

11. p=0.205, log rank testp=0.507, log rank test Siablis D, Karnabatidis D, Katsanos K, et al. Under peer review 2008 Patient survival & limb salvage

12. Angiographic results: Primary patency Cox proportional hazards regression analysis HR: 4.8, CI: 2.9-7.9, p<0.001 Siablis D, Karnabatidis D, Katsanos K, et al. Under peer review 2008 x5

13. Siablis D, Karnabatidis D, Katsanos K, et al. Under peer review 2008 HR: 0.38, CI: 0.25-0.58, p<0.001 Angiographic results In-stent restenosis Cox proportional hazards regression analysis x0.4

14. Siablis D, Karnabatidis D, Katsanos K, et al. Under peer review 2008 HR: 2.5, CI: 1.3-5.0, p=0.006 Re-do procedures Cox proportional hazards regression analysis x2.5

15. BaselineImmediate2-year

16. Conclusions Compared to bare metal stents, application of sirolimus-eluting stents in below-the-knee arteries significantly inhibits restenosis, improves long-term angiographic patency and reduces the need for repeat procedures due to clinical relapse

17. The Amputation, Thomas Rowlandson (1756-1827)