Future Directions and Development of DCB Systems Bruno Scheller Klinische und Experimentelle Interventionelle Kardiologie, Universität des Saarlandes, Campus Homburg Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes Homburg / Saar, Germany

Speaker’s name: Bruno Scheller X I have the following potential conflicts of interest to report: X Research contracts (B.Braun, MDT Invatec, AngioScore)  Consulting  Employment in industry X Stockholder of a healthcare company (InnoRa GmbH)  Owner of a healthcare company X Other(s): coinventor in several patent applications  I do not have any potential conflict of interest

J Am Coll Cardiol Intv 2012;5:1001–12

Drug Coated Balloons – Future Innovation Coating and balloon technology Crystalline vs. amorphous coating Balloon surface Dedicated balloon platforms for different vascular territories and indications Nanotechnology DCB and dissections Scoring balloon DCA + DCB DCB + bioabsorbable stents Alternative drugs Clinical evidence RCT in different indications and for different types of DCB No class effect ‘DEBonly’ concept

DCB - Mode of action Scheller, Heart 2007; 93: 539-41. Scheller, Circulation 2004; 110: 810-4. Speck, Circ Cardiovasc Interv 2012; 5: 392-400

Crystalline vs. amorphous paclitaxel on DCB Additive is an independent determinant of efficacy in animal models, despite the same dose of drug on balloon surface Restenosis quantified by late lumen loss at 1 month, normalized by restenosis of plain balloon angioplasty control; i.e., calculated by 1 - [(Late Loss of Control) – (Late Loss of Drug Coated Balloon Formulation)]/(Late Loss of Control). Slide adapted from Juan Granada 2013 6

Cosmetic improvements at the expense of efficacy? Alexander Rübben, from the Internet

Not all DCB are created equal “When presenting our first preclinical data on DCB about 10 years ago, people said it would never work in humans. Today, the greatest threat to this technology is bad clinical science. As mentioned in the ESC/EACTS guidelines for coronary revascularization, one cannot assume a class effect for DCB. Therefore, clinical evidence includes adequately powered RCTs in different indications for each type of DCB.” Cremers, Clin Res Cardiol 2009; 98: 325–330. SCAAR, Bondesson, EuroIntervention 2012; 8: 444-9. Scheller, Cardiovasc Revasc Med. 2012; 13: 257-9

Submitted

Drug Coated AngioSculpt May be able to deliver drug more effectively with a scoring element Better acute luminal results with AngioSculpt compared to POBA Lower rate of dissection with AngioSculpt compared to POBA No slippage or “geographic miss” with AngioSculpt May be able to avoid adjunctive stenting All of the above may allow a drug-coated AngioSculpt to provide “stand alone” therapy for a wide range of coronary and peripheral arterial lesions with a significantly lower restenosis rate than POBA or allow the use of BMS rather than DES AngioSculpt (coated) AngioSculpt (bare) In-Stent Restenosis (ISR) Non-slip (avoid “geographic miss”) Less tissue “recoil” More optimal re-expansion of original stent, improved initial lumen gain

Cardiovascular Revascularization Medicine 13 (2012) 219–223

Werner, LINC 2012

EuroIntervention 2011; 7: K17-22

Clin Res Cardiol. 2012. Circ Cardiovasc Interv. 2011; 4: 447-55

DCB + BMS ! geographical mismatch ! partikels between stent struts and vessel wall => (spot-)stent, DCB postdilatation Clin Res Cardiol 2010; 99: 165–174. EuroIntervention 2011; 7: K57-60. Hamm AHA 2009. Heart 2011; 97: 1338-42

DCB only DCB are not a replacement for DES. New platform for local drug delivery without the need for stent implantation. Predilatation Preparation of the lesion, identification of risk for dissections Final size (de-novo) or 0.5 mm smaller (ISR) Acceptable result, not stent-like Provisional BMS Spot-stenting for dissections type C-F DCB Balloon-Artery ratio 0.8-1.0 Nominal pressure, 30 seconds EuroIntervention 2011; 7: K125-8

Coronary de-novo - DCBonly J Am Coll Cardiol 2012; 60: 2473-80. J Am Coll Cardiol. 2012; 60: 1733-8.

DCBonly BIF - 54 year old male, unstable angina initial Predilatation, Carina shift SQP 3.0/15 SQP 3.0/20 Final result 6 months

New age of vascular therapy: Leaving nothing behind New technologies to avoid permanent implants in vascular therapies DCB Bioabsorbable Stents published Coronary > 4,300 (paclitaxel iopromide) > 440* (Absorb + AMS) Peripheral > 800 > 70 ongoing > 3,500 (paclitaxel iopromide) > 1,000 > 4,500 (paclitaxel urea) ? Clinical Evidence: # of pts in RCT and large registries. *no RCT, simple lesions TCT 2012. EuroIntervention 2011; 7: K7. Submitted for publication.