1. The new consensus document on peripheral DCB PTA Bernardo Cortese Intv’ Cardiology, A.O. Fatebenefratelli bcortese@gmail.com bernardocortese.com B. Cortese, J Granada, B Scheller, PA Schneider, G Tepe, D Scheinert, L Garcia, E Stabile, F Alfonso, G Ansel, T Zeller

2. Disclosure Statement of Financial Interest Grant/Research Support Consulting Fees/Honoraria Movi, AB Medica, Medtronic Cardionovum, Abbott Vascular, Concept Medicals, Acilia, The Medicines Company Within the past 12 months, I or my spouse have had a financial interest/arrangement or affiliation with the organizations listed below. Affiliation/Financial RelationshipCompany

3. German Drug-eluting Balloon Consensus Group (Kleber FX, Mathey DG, Rittger H, Scheller B) Euroint 2011 DCB consensus documents (coronary field) German Drug-eluting Balloon Consensus Group, II edition 2013 Drug-Coated Balloon Treatment of Coronary Artery Disease: A Position Paper of the Italian Society of Interv. Cardiology (B Cortese, S Berti, G Biondi et al.) Cath Cardiovasc Int 2013

4. Steering Committee: B Scheller, J Granada, T Zeller, B Cortese

5. -DCB have robust bench and preclinical data (peripheral and coronary) -Clinical data for peripheral intv’s is not robust and regards only a few available devices -Currently, scientific societies’ guidelines on DCB use in the peripheral field are not available Background

6. To provide a comprehensive framework to guide clinical practice and to discuss challenges and future perspectives in territories where a gold standard treatment is currently not available and current treatments are of limited efficacy. Reasons for a Consensus Document

7. G Biamino, LINC 2013

11. LEVANT 2 blinded follow up K Rosenfield, NEJM 2015

12. (p=0.001) LLL 20% 56% 10% 56% perc diam stenosis 2-Y TLR DCB may heal dissections... Tepe G., J Endovasc Ther 2013...without loosing their antirestenotic effect.

13. B Cortese ‘14

14. -Balloon insertion/navigation -Predilatation -Coverage of the entire lesion with DCB (healthy- to-healty) -Geographical mismatch. Fem-pop technical considerations ballooned

15. Predominance of BTK lesions (74% of all lower limb lesions) Prevalence of diffuse disease with long stenosis and occlusions (66% occlusions, 50% occlusions >10 cm) Graziani et al. Vascular Involvement in Diabetic Subjects with Ischemic Foot Ulcer: a New Morphologic Categorization of Disease Severity Eur J Vasc Endovasc Surg 33, 453 460 (2007) 1%8%14%36%11%27%1% BTK: 74% of 2893 lesions from 417 consecutive CLI diabetic subjects with ischemic foot ulcer CLI and Diabetes: disease extension and distribution

16. Author/trial/journalyeardevicelesion length (mm)number of devices used lesion numberCLI (%)Ruth 5 (%) Peeters2005AMS1120 10055 Boisiers AMS Insight Cardiov Interv Radiol 2008AMS/POBA10.6/12?74/7510073 Boisiers DESTINY J Vasc Surg2012EES/BMS15.9 +/-10.2 vs 18.9+/-10 86/9278/7610050 Karnabatidis J Endov Th2011EES/POBA+/-BMS77+/-70 vs 77+/+67332/86102/7210042 Commeau CCI2006SES27.6 (stent)621068733 Balzer J Cardiov Surg2010SES46+/-2234132010046 Rastan EHJ2011SES/BMS31+/-9120/1161614741 Scheinert Euroint2006SES/BMS<33 mm30/30606337 Siablis J Endov Th2007SES/BMS14/13?66/6510028 Werner J Endov Th2012SES33.6+/-14.6201?4332 Scheinert ACHILLES JACC2012SES/POBA26.9+/20.9 vs 26.8+/- 21.3 410113/115mandata email a Scheinert Feiring PARADISE JACC2010DES26.9+/-5.8 (stent)22811810061 (31 Class 6) Grant CCI2008DES24.8+/-10.9171250 Rosales CCI2008DES23412810050 Cioppa ?2008BMS72.2+/-11.723209550 Feiring JACC2004BMS?1978668? Deloose Euroint2009BMS52.2505610016 Donas Eur J CV Surg2009BMS65+/-9383410056 Rocha-Singh XCELL trial Viva 1 2010BMS47+/-42?14010082 Krankenberg CCI2000-(05)POBA?N/A18100 Schmidt JACC2011DEB173/183113 (?)1138264 Liistro DEBATE BTK TCT2012DEB/POBA128+/-83 vs 130+/-79?80/78100? Rutherford 5,6 Cortese CRT ‘13, unpublished data AMS av. LL 11 mm DES av. LL 38 mm DEB av. LL 238 mm!!!

17. Residual stenosis Balloon-angioplasty Focal stenting with DES Limitation of DES placement in long BTK-Lesions Follow-up courtesy of T. Zeller, 2015

18. BTK BTK First study (FreePAC tech) Schmidt et al, JACC 11 104 consecutive pts with CLI or IC (17.4%) binary rest after 3 months: 27% clinical improvement 1- y: 91% complete wound healing 1-y: 74% Restenosis typically focal

19. CLI + Diabetes 150 (Tibial) Lesions DEB (75 lesions) Std PTA (75 lesions) 12-month Angiographic and Clinical follow-up Aspirin + Clopidogrel (1 month) 24-month Duplex and Clinical follow-up random (1:1) Liistro et al., JACC 2014 BTK vs. POBA DEBATE BTK (FreePAC tech.)

20. IN.PACT DEEP (FreePAC tech.)

22. In.Pact Deep: lack of a surveillance program LEIPZIG Registry DEBATE BTK DCB (12-month) PTA (15 month) Deaths16.3%10.5% Limb Salvage95.6%100% Wound healing74.2%78.6% 12-month OutcomesDCBPTAp Deaths7.7%4.5%0.4 Major Amputation0%1.5%0.9 Wound healing86%67%0.01 Liistro F et al. Circulation. 2013 Aug 6;128(6):615-21 Schmidt A et al. J Am Coll Cardiol. 2011 Sep 6;58(11):1105-9 Schmidt A et al. Catheter Cardiovasc Interv. 2010 Dec 1;76(7):1047-54 “…once discharged, patients were followed in a multidisciplinary, dedicated foot clinic to facilitate healing process and recovery of the ambulatory function. Office visits were scheduled 2 days/week for the first 2 months, once a week for the third month and then every two weeks…” “…multiple factors contribute to wound healing and limb salvage, including local wound care and surveillance regimen, which may be equally as important as revascularization. It therefore may be difficult to prove the superiority of the DEBs over uncoated balloons for these clinical endpoints…”

23. -Really DIFFUSE disease (drug uptake) -Balloon insertion/navigation-consider a high drug loss -Predilatation -Geographical mismatch -Lower success ankle/foot lesions -BTK angioplasty: multidisciplinary team BTK-DCB: technical considerations

24. Peripheral DCB: health/economic evaluation Every 4 lesions treated (POBA/DCB) 1 TLR/24-mo AVOIDED with DCB US: $ 2870 saved Germany: E 662 saved US: $ 250.000.000 SAVED/y. Germany: E 30.500.000 SAVED/y.

25. Document key messages -Not all DCBs are created equal, even for the peripheral district. -Same tech considerations: predilatation, dissections. -Avoid stents if not strictly necessary. -BTK: RCT with newer gen. balloons, surveillance.

26. The new consensus document on peripheral DCB PTA Bernardo Cortese Intv’ Cardiology, A.O. Fatebenefratelli bcortese@gmail.com bernardocortese.com B. Cortese, J Granada, B Scheller, PA Schneider, G Tepe, D Scheinert, L Garcia, E Stabile, F Alfonso, G Ansel, T Zeller