RIBS VI: A Prospective, Multicenter, Registry of Bioresorbable Vascular Scaffolds in Patients With Coronary Artery Bare-Metal or Drug-Eluting In-Stent Restenosis Fernando Alfonso MD, PhD, FESC Hospital Universitario “La Princesa” Madrid. Spain. On Behalf of the RIBS VI Investigators Javier Cuesta MD, Fernando Rivero MD, María J. Pérez-Vizcayno MD, Bruno García MD, José R. Rumoroso MD, Francisco Bosa MD, Armando Pérez de Prado MD, Mónica Masotti MD, Raúl Moreno MD, Angel Cequier MD, Hipólito Gutiérrez MD, Arturo García-Touchard MD, José R López-Mínguez MD, Javier Zueco MD.

Disclosure Statement of Financial Interest I, [Fernando Alfonso, MD, and the coauthors], DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation

RIBS VI Background: Management of patients with in-stent restenosis (ISR) still remains a challenge. The role of bioresorbable vascular scaffolds (BVS) in these patients is unknown. However, the potencial benefits of their strong antiproliferative effects without the need of an additional permanent metal layer, make these devices an attractive strategy in this scenario.

RIBS VI Objective: To assess the efficacy of BVS in the treatment of patients with ISR. To compare BVS results with those obtained with drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in the RIBS IV and RIBS V RCT - Primary Endpoint: MLD at Follow-up - Clinical Endpoint: Combined (Cardiac D, MI,TVR/TLR) ClinicalTrials.gov ID: NCT02672878

RIBS VI Multicenter, Prospective, Angiographic FU 19 2 16 1 6 5 4 3 8 9 14 12 15 11 13 17 7 10 18 1.- Asturias, HU Central Asturias. 2.- Badajoz, HU Infanta Cristina.   3.- Barcelona, HU Bellvitge. 4.- Barcelona, HU Clinic. 5.- Barcelona, HU Sant Pau. 6.- Barcelona, HU Vall D’Hebrón. 7.- Canarias, HU de Canarias 8.- Cantabria, HU Marques de Valdecilla. 9.- Santiago Compostela, HU Santiago 10.- León, HU CA de León 11.- Madrid, HU 12 de Octubre. 12.- Madrid, HU La Paz. 13.- Madrid, HU La Princesa 14.- Madrid, HU Puerta de Hierro.  15.- Madrid, HU Ramón y Cajal. 16.- Málaga, HU Virgen de la Victoria. 17.- Toledo, H U Virgen de la Salud Toledo 18.- Valladolid, HU Clínico de Valladolid 19.- Vizcaya HU Galdakao Research Promotor: Spanish Society of Cardiology (SSC) Auspices: Working Group on Interventional Cardiology of the SSC Coordinator Center: H. Universitario La Princesa Madrid. Investigators´ driven initiative Unrestricted research grants: Abbott Vascular (StJude y Terumo)

RIBS VI Study Organization Coordinating Center: Hospital Universitario La Princesa. Madrid. Steering Committee: F. Alfonso (Chairman and Principal Investigator), J. Zueco, A. Cequier, C. Morís. Clinical Events Committee: R. Hernández, M. Sabaté. Coronary Angiography Core Laboratory: (Hospital Universitario La Princesa, Madrid) J. Cuesta, M.J. Pérez-Vizcayno. Data Coordination, Safety Monitoring and Statistical Committee: J. Cuesta, M.J. Pérez-Vizcayno, Cristina Fernández. Intravascular Ultrasound and Optical Coherence Tomography Committee: F. Alfonso J. Cuesta. Sites and Investigators: In order of enrollment: 1Hospital Universitario La Princesa, Madrid, (F. Alfonso, J. Cuesta, F. Rivero, T. Bastante, A. Benedicto, M. García-Guimaraes); 2Hospital Universitario Vall d’Hebron, Barcelona, (B. García del Blanco); 3Hospital Universitario de Canarias (F. Bosa); 4Hospital Galdakao, Vizcaya (J.R. Rumoroso); 5Complejo Asistencial Universitario de León, León, (A. Pérez del Prado); 6Hospital Universitario Clinic de Barcelona, Barcelona, (M. Masotti); 7Hospital Universitario Infanta Cristina, Badajoz, (J.R. López-Mínguez); 8Hospital Universitario de Valladolid, Valladolid (H. Gutierrez); 9Hospital Universitario de Bellvitge, Barcelona, (A. Cequier); 10Hospital Universitario Marqués de Valdecilla, Santander, (J. Zueco); 11Hospital Universitario Puerta de Hierro, Majadahonda, (A. García-Touchard); 12Hospital Universitario La Paz, Madrid, (R. Moreno); 13Hospital Universitario 12 de Octubre, Madrid, (T. Velazquez); 14Hospital Universitario Sant Pau, Barcelona, (V. Martí); 15Hospitalario Universitario Central de Asturias, Oviedo, (C. Morís); 16Hospital Ramón y Cajal, Madrid (R. Hernández); 17Hospital Universitario Virgen de la Salud Toledo, Toledo, (J. Moreu); 18Hospital Universitario Virgen de la Victoria, Málaga, (J.M. Hernández); 19Complejo Hospitalario Universitario de Santiago, Santiago de Compostela (R. Trillo)

Inclusion / Exclusion Criteria RIBS VI Inclusion / Exclusion Criteria Inclusion: Exclusion: Stent Related: Stent location undefined ISR <1 Month Thrombus Vessel diameter < 2.25 mm ISR outside the Stent General: Life expectancy < 1 y Female in childbearing age Problems FU angiography Intolerance DAT LVEF < 25% Informed consent Age 20 - 85 y ISR (> 50% stenosis) Angina or silent ischemia ISR amenable for BVS

Flow Diagram RIBS VI EES DEB BVS RIBS VI 249 Pts 219 Pts 223 Pts Same RIBS Centers Incl/Excl / Criteria Informed Consent RIBS VI Prospective, Angio FU (BMS-ISR and DES-ISR) 498 Pts ISR 309 Pts RIBS IV; 189 Pts RIBS V Randomization 249 Pts EES DEB 219 Pts Angio FU 223 Pts Mean: 257 days Mean: 270 days 100% Angio Success SeQuent Please (B. Braun) Xience Prime (Abbott Vascular) 498 1Y Clinical FU (100%) 442 Pts: 91% of Eligible QCA Primary End-point January 2010 August 2013 141 Pts BVS Absorb (Abbott Vascular) 100% Angio Success April 2014 December 2015 QCA (95% of Eligible) Primary End-point 134 Pts Angio FU 141 9Mo (100%); 124 (88%) 1Y (17 Pending) ClinicalTrials.gov Identifier: NCT01239953 & NCT01239940

Clinical Characteristics RIBS VI Clinical Characteristics BVS (141) DEB (249) EES (249) Age (years) 65+10 67+10 Female 16 (11) 40 (16) 37 (15) - Diabetes 72 (51)* 105 (42) 85 (34) - Hyperlipidemia 113 (80) 179 (72) 183 (74) - Hypertension 106 (75) 178 (72) 189 (76) Unstable Angina 69 (49) 118 (47) 121 (49) Stable Angina / Isch 72 (51) 131 (53) 128 (51) Time to ISR (median days) 1770* 496 535

Angiographic Data RIBS VI DEB (249) EES (249) BVS (141) - LAD 66 (47) 112 (45) 108 (43) - RCA 44 (31) 80 (32) 77 (31) - LCX 27 (19) 48 (19) 56 (23) DES-ISR 70 (51) 154 (62) 155 (62) Length ST (mm) 20±7 >1 Treatment of ISR 21 (15) 23 (9) 20 (8) LVEF (%) 56±13 58±12 59±11

Procedural Data RIBS VI DEB (249) EES (249) BVS (141) Device Length 19+8 20+6 21+9 Max Pressure (atm) 20+4 18+4 Inflation Time (sec) 60+50 108+48 62+46 B/A Ratio 1.20+0.2 1.23+0.2 1.19+0.2 Cross-over 0 (0) 13 (5) 1 (0.4) Success 141 (100) 249 (100)

QCA: In-Segment Analysis RIBS VI QCA: In-Segment Analysis Reference Diameter Lesion Length (mm) (mm) 2.7±0.5 2.6±0.5 2.7±0.5 12±6 12±7 12±6 p = 0. 29 p = 0.89 CAAS II System DEB BVS EES

QCA: MLD at FU In-Segment In-Lesion RIBS VI MLD-FU (Primary Endpoint) (mm) p < 0.001 In-Segment (Primary Endpoint) 1.87±0.5 1.88±0.6 2.16±0.7 Seg Lesion p < 0.001 1.94±0.5 1.94±0.6 2.30±0.7 In-Lesion DEB BVS EES

QCA: In-Segment RIBS VI Acute Gain Late Loss 1.47 1.24 1.16 0.24 0.23 p < 0.001 p < 0.05 (mm) (mm) 1.47 1.24 1.16 0.23 0.24 0.12 DEB BVS EES

__ RIBS VI MLD (mm) (%) DEB EES BVS PRE FU POST p = 0.03 p <0.001

__ RIBS VI (%) Stenosis (%) DEB EES BVS POST PRE FU p < 0.001 35 (16%) 19 (9%) 15 (11%) p = 0.07 PRE p = 0.008 p < 0.001 FU p < 0.001 __ BVS DEB EES (%) Stenosis

RIBS VI On multivariate analysis, after adjusting for all potential confounders: - MLD at FU was significantly smaller - % DS at FU was significantly larger after BVS compared with EES treatment

Events at Final FU (1 Year) RIBS VI Events at Final FU (1 Year) 141 Pts (100%) 10 Mo FU; 1Y FU 124 Pts (88%) (17 Pts pending 1Y) 20 (%) 19 (13.5) 15 16 (11.3) 10 5 4 (2.8) 1 (0.7) 0 (0) Death Def/Pr ST AMI TLR TVR AMI: 1 periprocedural; 1 definitive BVS thrombosis 1 late SB closure; 1 definitive ST of a stent in another vessel segment

91% 86% 85% __ RIBS VI Freedom from Cardiac Death, MI, TVR 100 86% 80 Breslow, p = 0.12 Log Rank, p = 0.14 85% 60 __ BVS DEB EES 40 20 Freedom from Cardiac Death, MI, TVR 1 2 3 4 5 6 7 8 9 10 11 12 Time (months)

94% 87% 87% __ RIBS VI Freedom from Cardiac Death, MI, TLR 100 87% 80 Breslow, p = 0.02 Log Rank, p = 0.03 87% 60 __ BVS DEB EES 40 20 Freedom from Cardiac Death, MI, TLR 1 2 3 4 5 6 7 8 9 10 11 12 Time (months)

97% 89% 89% __ RIBS VI Freedom from TLR Time (months) % DEB EES BVS 100 89% 80 89% Breslow, p = 0.002 Log Rank, p = 0.002 60 __ BVS DEB EES 40 20 Freedom from TLR 1 2 3 4 5 6 7 8 9 10 11 12 Time (months)

RIBS VI Conclusions: BVS are safe and effective in the treatment of selected patients with ISR BVS provide favorable late angiographic (restenosis rate 11%) and clinical results (TLR 11%) in these patients The acute and late angiographic findings of BVS appear to be similar to those obtained with DEB (“leave nothing behind strategy”) but poorer than those seen after EES implantation (caution required as historical controls from RCT were used) Further studies with long-term follow-up will be required to elucidate the relative value of BVS vs other well-established therapeutic strategies in this challenging setting