Real world usage of BVS in Europe Corrado Tamburino, MD, PhD Chief of Cardiovascular Department, Ferrarotto Hospital, University of Catania, Catania, Italy

Corrado Tamburino, MD I have the following financial relationships:   I have the following financial relationships: Speaker honoraria Abbott Vascular, Medtronic, Advisory Board: Abbott Vascular, Medtronic Stockholder: Edwards

Coronary stent approval pathways in Europe and in the US Byrne RA et al. Eur Heart J 2015;36:2608–2620.

Bioresorbable scaffolds Commercially Available Reva ReZolve Biotronik DREAMS-2 Abbott Vascular Absorb ART Amaranth Fortitude Elixir DESolve Template Thickness Tyrosine-derived Polycarbonate PLLA PLA-based PDLA PLLA Magnesium Template Thickness ~150 m ~150 m ~122 m X 2 ~160 m ~150 m ~125 m Support Time 6 months 3 – < 6 months ~6 months  3 months 3 – 6 months  3 months I2DAT, I2DT, PCL, Tyrosine Degradation Products Soft Hydroxyapatite H2O & CO2 H2O & CO2 H2O & CO2 H2O & CO2 Resorption Time < 36 months 18 – 24 months ~ 36 months ~18 months > 48 months 9 – 12 months (slow) (fast) (slow) (very fast) (very slow) (very fast)

Absorb Studies Real World and complex patient populations Randomized Controlled Clinical Trial Absorb Studies Real World and complex patient populations ALL-COMERS COMPLEX POPULATIONS GABI-R Design: All-comers registry N=5000 1˚: Safety & efficacy AIDA Design: RCT vs XIENCE N=2690 1˚: 2-year TVF POLAR-ACS Design: ACS registry N=100 1˚: Safety, clinical device, procedure, success & in-hospital MACE ABSORB CTO Feasibility: CTO N=35 1˚: Safety & performance FEAST Russia Registry Design: All-comers registry N=2500 1˚: 1-year MACE, TVF, Revascularization, ST, Peri-procedural MI, Angina FRANCE ABSORB Feasibility: De novo lesions N=2000 1˚: 1-year MACE PABLOS Feasibility: Bifurcations N=30 1˚: Device, procedural, main & side branches ISAR ABSORB MI Design: Non-inferiority vs EES N=260 1˚: % diameter stenosis at 6-8 months ABSORB FIRST Design: Prospective, multi-center, global registry N= ~1800 1˚: ST, CD, MI, revascularization, MACE, TLF, & TVF REPARA Design: All-comers registry N=1500 1˚: 1-year MACE IT-DISAPPEARS Design: MVD and Long Lesion Registry N=1000 1˚: Safety & efficacy PRAGUE 19 Design: STEMI (STEMI Killip I/II) N=100 1˚: Clinical outcomes BVS EXPAND* Design: All-comers registry N=300 1˚: 1-year MACE GHOST EU Design: All-comers registry N=continuous enrollment 1˚: TVF COMPARE ABSORB Design: High risk for ISR N=2100 1˚:TLF TROFI II Design: STEMI vs XIENCE N=190 1˚: 6-month, neo-intimal healing score Kuwait Registry Design: All-comers registry N=200 1˚: Safety & efficacy EVERBIO II Design: Non-inferiority RCT EES vs BES vs BVS N=240 1˚: Late lumen loss at 9 months PROSPECT Design: RCT BVS vs OMT in unstable asymptomatic pts N=900 1˚: 2-Yr IVUS MLA ASSURE Design: All-comers registry N=180 1˚: Safety & efficacy UK REGISTRY Design: Prospective, single-arm, multi center, observational registry N= 1000 1˚: RDS < 50% at procedure conclusion, MACE SIMPLE TO MODERATELY COMPLEX POPULATIONS ABSORB II Design: Randomized 2:1 Absorb BVS:XIENCE N=501 1˚: Vasomotion & lumen diameter after the index procedure & at 3 years ABSORB EXTEND Design: Prospective, single-arm, open-label clinical study N=800 1˚: ID-MACE ABSORB COHORT B Design: Allocated (non-randomized) N=101 1˚: Safety & performance ADDITIONAL LARGE RCTs ABSORB III Design: RCT N= ~2250 1˚: TLF at 1 year ABSORB JAPAN Design: RCT N= ~400 1˚: TLF at 1 year ABSORB CHINA Design: RCT N= ~440 1˚: In-segment late loss at 1 year ABSORB IV Design: RCT N= ~3000 1˚: Angina within 1 year *Excludes STEMI patients. ACS, acute coronary syndrome; MVD, multi-vessel disease; CTO, chronic total occlusion; MI, myocardial infarction RCT, randomized controlled trial; OMT, optimal medical therapy; EES, everolimus-eluting stents; BVS, bioresorbable vascular scaffold; STEMI, ST-segment–elevation myocardial infarction; MACE, major adverse cardiac events; ID-MACE, ischemia-driven major adverse cardiac events; TLF, target lesion failure; IVUS MLA, intravascular ultrasound minimal lumen area; TVF, target vessel failure; LAD, left anterior descending; FIM, first-in-man. Information contained herein for presentation outside the US only. Not for distribution. Absorb BVS is currently CE marked. Please check the regulatory status of the device prior to use in countries where CE mark is not the regulation in force. ©2015 Abbott. All rights reserved. AP2941513-OUS Rev. A

Participating centers (n=11) Elisabeth Krankenhaus, Essen C. Naber S. Pyxaras University of Giessen, Giessen H. Nef Medizinische Klinik, Mainz T. Gori Royal Brompton Hospital, London C. Di Mario A. Mattesini Uniwersytet Medyczny, Poznan M. Lesiak A. Araszkiewicz San Raffaele Hospital and Emocolumbus Clinic, Milan A. Colombo A. Latib Klinikum Großhadern, Munich J. Mehilli Biomedical Investigation Institute, IDIBAPS, University of Barcelona M. Sabatè S. Brugaletta Ferrarotto Hospital, Catania C. Tamburino D. Capodanno P. Capranzano S. G. Di Dio Hospital, Agrigento G. Caramanno S. Geraci Tamburino C, et al. on behalf of GHOST-EU investigators

Patient Population (n=1,477) Age, years±SD 62±11 (1,477) Male 1180/1,477 (80%) Diabetes mellitus 381/1,477 (26%) On insulin 134/1,450 (9%) Hyperlipidemia 778/1,477 (53%) Hypertension 1070/ 1,477 (72%) Smoker 448/1,477 (30%) Previous PCI 497/1,477 (34%) Prior CABG 71/1,477 (5%) Stroke/TIA 53/1,477 (4%) ACS 697/1,477 (47%) NSTEMI 259/1,477 (18%) STEMI 248/1,477 (17%) LV ejection fraction <30% 38/1219 (3.1%) eGFR<60 mL/min 135/934 (14%) Overall Patients N=1,477; 1,736 lesions 30-day FU* N= 1,444/1,477 (97.8%) 6-month FU* N=1397/1,477 (94.6%) 12-month FU* N=1276/1,477 (86.4%) Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

Lesion characteristics (n=1,736) Vessel treated LMCA 20/1,715 (1.2%) LAD 821/1,704 (48%) LCX 415/1,703 (24%) RCA 447/1,705 (26%) Vessel diameter (n=1,224) RVD (mm) 3.0±0.53 RVD ≤ 2.5 mm 275 (22.5%) RVD ≥ 3.5 mm 278 (22.7%) Mean lesion length (n=1,215) 19.5±14.0 Length > 34 mm 139 (11.4%) Lesion ACC/AHA B2/C 857/1614 (53.1%) Bifurcation 366 (21.1%) CTO 113/1736 (6.5%) ISR 54/1736 (3.1%) Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

CV death, target-vessel MI, clinically-driven TLR Target Lesion Failure CV death, target-vessel MI, clinically-driven TLR 5.2% 1.8% 3.4% Days 0 90 180 365 Pts at risk 1,477 1,376 1,323 999 Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

Clinically-driven target vessel revascularization 2.3% 4.1% 1.1% 3.8% 6.2% 1.5% Days 90 180 365 Pts at risk 1,381 1,329 996 Pts at risk 1,331 1,274 963 Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

Cardiovascular mortality and target-vessel MI 0.8% 0.9% 0.6% 2.0% 2.4% 1.2% Days 90 180 365 Pts at risk 1,398 1,350 1031 Days 90 180 365 Pts at risk 1,377 1,328 1009 Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

Scaffold Thrombosis Definite/probable 1.9% 2.0% 1.4% Days 0 90 180 365 Pts at risk 1,477 1,376 1,332 1,012 Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

Procedural characteristics Pre-Dilatation 1670/1736 (96.2%) Cutting balloon 21/1723 (1.2%) Scoring balloon 47/1722 (2.7%) Residual DS ≥ 40% after pre-dilatation 254/911 (28%) Post-Dilatation 908/1736 (52.3%) Mean Scaffold Diameter/Les 3.1±0.80 Mean scaffold Length/Les (n=1722) 27.6±16.7 N. of scaffold/Les 1.28±0.64 Overlapping/Les 364/1736 (21%) OCT* 206/1498 (14%) IVUS* 240/1498 (16%) *per patient; DS: diameter stenosis * Residual in-scaffold diameter stenosis < 30% Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

The Four ‘Ps’ For Optimal BVS Implantation Prepare the Lesion Possibly with a NC balloon (balloon/RVD 1:1) 2. Properly Size the Vessel Use IC nitro, imaging if necessary, balloon sizing, plan to upsize the scaffold for any RVD by visual estimation. 3. Pay Attention to Expansion Limits Stay within the nominal size (+0.5mm), 2 atm increments every 5 seconds. Mantain target pressure for 30 seconds. 4. Post-Dilate with a Non-Compliant Balloon at high pressure Aim at <10% residual stenosis after scaffold implantation.

Predictors of TLF Diabetes mellitus 2.09 (1.28-3.41) 0.003 Hyperlipidemia 0.65 (0.40-1.05) 0.08 ACS at presentation 1.84 (1.11-3.04) 0.02 Bifurcation 1.50 (0.89-2.52) 0.13 In-stent restenosis 2.13 (0.77-5.93) 0.15 Ostial lesion 2.61 (1.31-5.23) 0.007 Total Scaffold length per patient 1.01 (1.00-1.02) Prasugrel or Ticagrelor use* 1.27 (0.78-2.07) 0.34 Tamburino C, et al. on behalf of GHOST-EU investigators; PCR 2015

1:1 case-control propensity score matching Study Design GHOST-EU1 N=1,189 from 10 EU sites XIENCE V USA2 N=5,034 from 162 US sites 1:1 case-control propensity score matching Non-parsimonious logistic regression model encompassing 26 variables GHOST-EU N=905 XIENCE V USA Matching ratio 0.76 Matching ratio 0.18 1 Capodanno D, et al. EuroIntervention. 2015;10:1144-53 2 Krucoff MW, et al. J Am Coll Cardiol Intv 2011;4:1298–309

Patients Characteristics (matched) ABSORB (n=905) XIENCE V (n=905) P value Demographics Age - mean ± SD, yrs 63 ± 11 0.57 Male sex - % 78 1.00 Risk factors Diabetes - % 28 27 0.82 Renal disease - % 16 19 0.10 Clinical presentation Acute coronary syndrome - % 42 43 0.92 Multivessel disease - % 58 60 0.41 Lesion characteristics ACC/AHA B2/C lesions - % 55 0.96 De novo - % 95 Chronic total occlusion - % 8 0.86 Ostial - % 11 0.06 Bifurcation - % 22 23 0.79 Lesion length – mean ± SD, mm 20 ± 15 20 ± 13 0.65 RVD – mean ± SD, mm 3.0 ± 0.5 0.49 Diam. stenosis– mean ± SD, % 85 ± 13 85 ± 11 Procedure details Post-dilatation - % 52 51 0.64 Tamburino C, et al. JACC Cardiovasc Interv 2016

12-Month Clinical Outcomes P=0.12 P=0.025 P=0.07 P=0.22 P=0.23 Tamburino C, et al. JACC Cardiovasc Interv 2016

GHOST-EU and the ABSORB trials GHOST-EU (n=905) ABSORB III (n=1,322) ABSORB II (N=335) A-JAPAN (N=266) A-CHINA (N=241) Age - mean ± SD, yrs 62 ± 11 64 ± 11 62 ± 10 67 ± 9 57 ± 11 Male sex - % 79 71 76 72 Diabetes - % 25 32 24 36 Acute coronary syndrome - % 47 27 (UA) 20 (UA) 10 (UA) 65 (UA) ACC/AHA B2/C lesions - % 54 69 46 NA In-stent restenosis - % 4 Excluded Chronic total occlusion - % 8 Ostial - % 9 Bifurcation - % 27 Lesion length – mean ± SD, mm 20 ± 15 13 ± 5 14 ± 7 14 ± 5 14 ± 0 RVD - mean ± SD, mm 3.0 ± 0.5 2.7 ± 0.5 2.6 ± 0.4 2.7 ± 0.4 2.8 ± 0.4 Post-dilatation - % 51 66 61 82 63 Target lesion failure - % 5.8 7.8 4.8 4.2 3.4 Definite or probable ST - % 1.8 1.5 0.6 0.4

Lipinski MJ et al. J Am Coll Cardiol Intv 2016;9:12–24.

Outcome rates of patients with BVS Meta-Analysis of ABSORB studies 10,510 patients (8,351 with a BVS and 2,159 with DES) Follow-up: 6.4±5.1 months Outcome rates of patients with BVS Lipinski MJ et al. J Am Coll Cardiol Intv 2016;9:12–24.

Characteristics of main real-world BVS registries GHOST EU GABI-R REPARA ABSORB FIRST Diabetics 27% 21% 24.4% 24% Ostial Lesions 5.2% 1.2% - 5.7% ACS 47% 50% 78% 41% AMI 34% 38% 59% 26% Bifurcations 3.8% 13% CTO 6.5% 10% Mean Lesion Length (mm) 19.5±14.0 18.5 ± 9.3 Lesion Length >34 mm 11.4% 5.9% Mean Scaffold length (mm) 27.6±16.7 27.6±17.0 23.0±13.3 Post-dilatation 52.3% 66.8% 40% 46.5% OCT use 14% 4% 9.1% IVUS use 16% 5% 2.8%

Outcomes of main real-world BVS registries GHOST EU GABI-R REPARA ABSORB FIRST Patients 1,477 1536 1479 958 Follow-up 1 year 30 days Cardiac Mortality 0.9% 0.1% 0.34% 0.5% Myocardial infarction 2.4% 1.4% 1.56% 1.7% Target lesion failure 5.2% - 2.2% MACE 1.8% 2.6% Definite/Probable scaffold thrombosis 2.0 1.0% 0.88% 0.8%

Conclusions The all-comers usage of BVS in Europe has been associated with overall favorable outcomes at mid-term. European registries results have suggested the procedure optimization and accurate lesion selection are key for improving outcomes with BVS. Further research focusing on this is needed. Long-term follow-up data on BVS in complex settings are needed