DCB for In-Stent Restenosis: Is It Superior to DES? Robert A. Byrne MB BCh PhD FESC CRT, Washington, D.C. | 20th February 2017

Disclosures Lecture fees: B. Braun Melsungen, Biotronik, Boston Scientific Institutional research grants: Boston Scientific, Heartflow

Is DCB Superior to DES for In-Stent Restenosis? Agenda Is DCB Superior to DES for In-Stent Restenosis? Device selection overview BMS in-stent restenosis DES in-stent restenosis Take home message Byrne, R.A. | CRT Washington, D.C. | 20th February 2017

Vascular Brachytherapy Cutting/Scoring Balloon ISR: Device Selection Plain Balloon PTCA Vascular Brachytherapy Cutting/Scoring Balloon Atherectomy Drug-Coated Balloon Drug-Eluting Stent

ISR Network Meta-analysis Rankogram of PCI strategies for any type of ISR for %DS, binary restenosis, and TLR Siontis et al. | Lancet 2015

Is DCB Superior to DES for In-Stent Restenosis? Agenda Is DCB Superior to DES for In-Stent Restenosis? Device selection overview BMS in-stent restenosis DES in-stent restenosis Take home message Byrne, R.A. | CRT Washington, D.C. | 20th February 2017

The more you gain, the more you lose! Endpoints: DCB vs DES Achtung! When comparing balloons against stents late loss is not a valid angiographic endpoint The more you gain, the more you lose! Siontis et al. | Lancet 2015

PEPCAD II ISR Study: Results BMS-ISR: DCB vs DES PEPCAD II ISR Study: Results Late Loss Minimal Lumen Diameter Unvedorben et al. Circulation 2009

BMS-ISR: DCB vs G2 DES - RIBS V Primary Endpoint: MLD at FU MLD-FU DCB EES p < 0.0001 2.36 2.01 (mm) In-Segment Seg Lesion MLD-FU (mm) p < 0.0001 2.44 2.03 In-Lesion Alfonso et al. JACC 2014

TIS Trial: BMS In-stent Restenosis DCB is Superior to DES…or is it? The starting position was not the same! Pleva et al. | Circ Cardiovasc Interv. 2016

Is DCB Superior to DES for In-Stent Restenosis? Agenda Is DCB Superior to DES for In-Stent Restenosis? Device selection overview BMS in-stent restenosis DES in-stent restenosis Take home message Byrne, R.A. | CRT Washington, D.C. | 20th February 2017

DES-ISR: DCB v DES v Angioplasty Diameter Stenosis at Follow-up Angiography 100 Paclitaxel-Eluting Balloon (PEB) Paclitaxel-Eluting Stent (PES) 80 Balloon Angioplasty (BA) 60 PEB versus BA PES versus BA Psuperiority <0.001 PEB 38.0% Cumulative Frequency (%) 40 PES 37.4% BA 54.1% 20 PEB versus PES Pnon-inferiority =0.007 20 40 60 80 100 Diameter Stenosis at Follow-up Angiography (%) ISAR-DESIRE 3: Intracoronary Stenting and Angiographic Results: Drug Eluting Stents for In-Stent Restenosis: 3 Treatment Approaches; Byrne et al. Lancet 2013

DCB for in-stent restenosis the comparable performance of DCB and repeat stenting with DES is important: by obviating the need for additional stent implantation, DCB therapy may be the preferred treatment option for this indication

DES-ISR: DCB Angioplasty Open question after ISAR-DESIRE 3 Comparative efficacy data versus newer generation DES Incremental value of scoring balloon pre-dilation Long-term outcome data from patients treated for DES-restenosis

DES-ISR: DCB Angioplasty Open question after ISAR-DESIRE 3 Comparative efficacy data versus newer generation DES Incremental value of scoring balloon pre-dilation Long-term outcome data from patients treated for DES-restenosis

RIBS-IV: DES-ISR: DCB v G2 DES QCA: MLD at FU Alfonso et al. JACC 2015 MLD-FU EES DEB p = 0.004 (mm) 2,5 2 2.03 1,5 1.80 1 In-Segment (Primary Endpoint) 0,5 Seg Lesion MLD-FU (mm) p < 0.001 2,5 2 2.20 1.89 1,5 1 In-Lesion 0,5

DES-ISR: DCB Angioplasty Open question after ISAR-DESIRE 3 Comparative efficacy data versus newer generation DES Incremental value of scoring balloon pre-dilation Long-term outcome data from patients treated for DES-restenosis

ISAR-DESIE 4: Primary Endpoint Diameter Stenosis at Follow-up Angiography 100 Scoring-balloon 80 Control P= 0.047 60 Cumulative Frequency (%) 40 40.4% ± 21.4 20 35.0% ± 16.8 20 40 60 80 100 Diameter Stenosis at Follow-up Angiography (%) ISAR-DESIRE 4: Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-Stent Restenosis 4

DES-ISR: DCB Angioplasty Open question after ISAR-DESIRE 3 Comparative efficacy data versus newer generation DES Incremental value of scoring balloon pre-dilation Long-term outcome data from patients treated for DES-restenosis

ISAR-DESIRE 3: Results at 3 years TLR TLR Death/MI Death/MI ISAR-DESIRE 3 | Kufner et al. | JACC Interv 2015

Key question Is this degree of decrement in antirestenotic efficacy allowable in order that additional stent implantation might be avoided?

Upcoming data

Prospective, multicenter, single arm ISAR-DESIRE 3A (Intracoronary Stenting and Angiographic Results: Drug Eluting Stent In-Stent Restenosis: 3A) 01.2015 09.2016 09.2017 ISAR-DESIRE 3A Prospective, multicenter, single arm n = 125 pts Enrollment & Follow-Up 1 Y Population: N= 125 patients with symptoms and/or objective signs of ischemia present and Restenosis at the site of previous limus-analogue DES implantation. Historical-control trial comparing to conventional paclitaxel-coated balloon with iopromide excipient (SeQuent Please PCB, B. Braun; data from ISAR-DESIRE 3) Primary Outcome: In-segment percent diameter stenosis (%DS) at 6-8 month follow-up angiography Principal investigators: Deutsches Herzzentrum München: Dr. Robert Byrne, Prof. Adnan Kastrati Klinikum Landshut: Prof. Bernard Zrenner

Is DCB Superior to DES for In-Stent Restenosis? Take Home Message Is DCB Superior to DES for In-Stent Restenosis? Two strategies should be considered: PCI with EES because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer At DHZ if the mechanical integrity of the stent is preserved, DCB is the default strategy Siontis et al. | Lancet 2015

Thank you for your attention!

Thank you for your attention! Robert A. Byrne MB BCh PhD FESC

SCAAR data shows promising outcomes for Pantera Lux vs key competitors Lagerqvist, oral presentation, TCT 2013

Target Lesion Revascularization Secondary Endpoint Binary Restenosis Target Lesion Revascularization P =0.03 P = 0.25 % % Scoring balloon Control Scoring balloon Control ISAR-DESIRE 4: Intracoronary Stenting and Angiographic Results: Optimizing Treatment of Drug Eluting Stent In-Stent Restenosis 4 36