1. Drug Coated Balloons From Bench to Bedside Service de Radiodiagnostic et Radiologie Interventionnelle Université de Lausanne Salah D. Qanadli, MD, PhD, FCIRSE Cardio-Thoracic and Vascular Unit, QMI Lab Department of Radiology CHUV-University of Lausanne

2. Potential Conflict of Interest Educational grants – Cordis, Boston Scientific, Medtronic, Invatec, Bard Research grants – Abbott Vascular, Biotronik, Cordis, St Jude Medical Consultancy –Mediar Ltd. –University of Kingston London –Cook, Optimed, Cordis, Bard, Abbott, Terumo –Bioclinica

3. Dotter’s Predictions in World’s First PTA* – Balloon angioplasty – Recanalization devices – Outpatient PTA – Cost saving relative to surgery – Endovascular “splints” (stents) that “reintimalize” (endothelialize) Dotter et al., Circulation, 1964

4. PTA in 2013 for PAD Critical issues –Immediate technical results - Immediate out-come -Flow limiting dissection -Elastic Recoil -Immediate technical success -CTO recanalization –Re-stenosis (mid and long-term patency) DCB Technology

5. DCB Mechanism of Action 1.30-second minimum inflation transfers drug to endoluminal surface 2.PTX diffuses into the arterial wall from an endoluminal reservoir 3.Over time, therapeutic drug levels are sustained in deep cell layers after endothelial drug levels become sub-therapeutic 4.Drug continues to inhibit restenosis in arterial wall while allowing the lumen to restore and re-endothelialize

6. LUTONIX Pre-clinical data

7. Coating uniformity European Product, Data on file. 6x60 mm Lutonix Drug Coated Balloon – N=5 6x60 mm In.Pact Admiral-Paclitaxel-eluting PTA balloon catheter – N=5

8. Defining Indications for DCB Clinical needs Device availability Proof of concept Clinical evaluation Strategy for use/Cost-effectiveness

9. Defining Indications for DCB Clinical needs –Clinically driven concept -High risk of re-stenosis -Femoro-popliteal lesions -up to 60 % at 12 mo* -Small vessels BTK -up to 69%** -AV Dialysis access -Re-stenosis/occlusion up 62 % at 12 mo*** *Muradin GS et al., Radiology, 2001. **Krokidis M et al., Cardiovasc Intervent Radiol, 2012. ***Bittl JA, JACC Cardiovascular Interv, 2010.

10. Defining Indications for DCB Clinical needs -Clinically driven concept -Limitations of existing alternatives (Stents, including DES) -BTK ? -BTA -AV shunts -FP -ISR -Complex anatomy (bifurcations, trans-collateral approaches,…) -Over dependence of double anti-agregants

11. Defining Indications for DCB Technology safety/efficacy –Proof of concept -Paclitaxel coated balloon (PCB) -DCB in routine practice in 2013 is PCB ! Clinical evaluation –Level of Evidence Cost-effectiveness –Strategy for use

12. De-Novo Femoro-popliteal Lesions N=433 ptsUncoated BPaclitaxel CBp TLR (n=350)27.7 %12.2 %<0.00001 RR (n=233)45.5 %18.7 %<0.0001 LLL (n=307)0.61-1.7 mm-.05-.05 mm<0.00001 Mortality (n=358)4.8 %2.1 %0.95 Adjunctive Stents (cross over) 14 to 34 %4 to 21 % THUNDER FemPac LEVANT I PACIFIER Control arm: UB ! Median FU: 10.3 mo Exclusion: Severely impaired arterial out flow

13. BTK Lesions BTK RCTTarget segmentArmsPE/FUNb PtsEstimated completion PICCOLOBTKPCB vs UB6 mo-18 mo114April 2011 IN.PACT DEEP NCT00941733 BTKPCB vs (UB+pStent) 12 mo357December 2015 DEBATE BTKBTKPCB vs UB12 mo150 DEBELLUMSFA/BTKPCB vs UB6 mo50 EURO CANAL NCT01260870 BTKPCB vs UB6 mo120December 2017

14. AV Dialysis Access 6 moUncoated BPaclitaxel CBp Primary patency rate25 %70 %<0.001

15. In-Stent Re-Stenosis Ongoing ISR RCTTarget segment ArmsFUNb PtsEstimated completion FAIR NCT01305070 SFA ISRPCB vs UB6 mo (DUS)118June 2013 ISAR PEBIS NCT01083394 SFA ISRPCB vs UB6 mo70July 2013 PACUBA I NCT01247402 SFA/PPA ISRPCB vs UB12 mo (DUS, CTA)60December 2012

16. Who is the best candidate for PCB ? AV Dialysis Access ISR BTK/BTA

17. What doses the future hold ? AV Dialysis Access ISR BTK/BTA

18. “Good judgment is based on experience Martin J. Lipton and experience is based on bad judgment”