Clinical outcomes after implantation of Absorb BVS in small vessels Clinical outcomes after implantation of Absorb BVS in small vessels. Results from the Italian RAI multicenter registry Giulia Masiero, MD1 Giuseppe Tarantini MD; Attilio Varricchio MD; Alfonso Ielasi MD; Bernardo Cortese MD; Paola Tellaroli PhD and Giuseppe Steffenino MD on behalf of the RAI Investigators 1Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School

Disclosure Statement of Financial Interest I, Giulia Masiero 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.

MPS EVIDENCE RISK OF MACE AFTER PCI Study/Sub category Treatment n/N Control OR 95% CI PES vs BMS TAXUS V 20/106 25/93 0.63(0.32,1.23) SES vs BMS SES-SMART 11/129 39/128 0.21(0.10,0.44) EES vs PES SPIRIT 2-3 19/366 17/159 0.46(0.23,0.91) SES vs PES SIRTAX 28/241 55/264 0.50(0.30,0.82) Total Events 78/842 136/644 0.43(0.32,0.59) A small vessel diameter is a well recognised indipendent predictor of a higher rate of in-stent restenosis and poorer clinical outcomes with MPS. RISK OF ANGIOGRAPHIC RESTENOSIS AFTER PCI LARGE (>3.25 mm) SMALL (<2.75 mm) POBA 20-35% 15-20% 35-55% BMS 15-20% 10-30% 25-50% DES 5-12.5% 2.5-7.5% 0-5% 20-30% 10-20% 5-10% 30-35% 20-25% 10-15% Small vessel coronary artery disease is a recognized challenging subset within the field of coronary artery intervention, even though the use of DES in this setting has led to more acceptable long-term results compared with balloon angioplasty and BMS. But a a high degree of vessel stretch and injury, (2) a smaller postprocedural lumen area, and (3) a higher metal density have all been proposed as a contributing factors to explain the poorer outcomes associated with SVs. Current consensus is however that the bigger is better paradigm is likely to be the most plausible mechanism to explain poorer aoutcomes associated with SV disease (smaller vessel size would be less able to accomodate the same absolute volume of neointimal hyperplasia as a larger vessel with the resultant increase in the rate of binary restenosis) relatively high late loss (eg EndeavorTM) medium late loss (eg TaxusTM) low late loss (eg CypherTM or XienceTM) “BIGGER IS BETTER” PARADIGM Biondi-Zoccai G. et al. Cardiovasc Revasc Med 2010;11:189–98

BVS PERSPECTIVE Post-Procedure 6-Months 2-years 5-years Despite the current thick strut BVS, the progressive loss in scaffold structural integrity leads to proven return of the vasomotion properties, positive remodelling and late lumen enlargement that may play a role in the prevention of EVENTS in the small lesion subset 5-years Cohort B OCT images – courtesy of RJ Van Geuns; Erasmus Medical Center Karanasos A et al. JACC 2014 Dec;64 (22):2343-56

BVS EVIDENCE Cohort B2, 1-year follow-up Cohort B1, 2-year follow-up Small Vessels (<2.5 mm) (N=21)(L=21) Large Vessels (≥2.5 mm) (N=35)(L=36) P Value (≥2.5 mm) (N=35) (L=36) The NET GAIN index 0.41±0.18 (20) 0.34±0.12 (34) 0.0564 0.43±0.14 (18) 0.35±0.16 (19) 0.1040 The LOSS index 0.23±0.32 (19) 0.20±0.22 (34) 0.8311 0.21±0.15 (18) 0.23±0.22 (20) 0.7041 Neointimal Hyperplasia area (mm2) 0.16±0.24 (21) 0.05±0.09 (35) 0.0556 0.25±0.26 (19) 0.23±0.28 (19) 0.4813 ((((Absorb cohort B vessel size 2.5 vs 3.0 with BVS 3.0: larger relative gain correlates with an higher degree of vessel injury during the index procedure (disruption internal elastic membrane) small vess are less amenable to accomodate the same absolute amount of neointimal tissue compared with large vessel)))) Encouraging long term clinical and angiographic results in small vessel as been shown in this post-hoc analys of the Absorb cohhort B trial, maybe explained by a favourable balanced between vessel injury and luminal expansion and late lumen enlargement. More results are needed in bigger and more complex population. Diletti R et al. Heart 2013 Jan;99(2):98-105

“Registro ABSORB Italiano” DESIGN: ongoing, spontaneous, multicenter, prospective data collection on consecutive patients undergoing Absorb BVS implantation in Italy OBJECTIVE: To evaluate the long-term safety and efficacy of Absorb BVS within an unrestricted cohort of patients undergoing PCI PRINCIPAL INVESTIGATOR: Giuseppe Steffenino, MD (Cuneo, Italy) Cortese B et al. Cardiovasc Revasc Med. 2015 Sep; 16(6):340-3

“Registro ABSORB Italiano” Flow algorithm Succesful BVS implantation Patient signs informed consent Enrolment in the RAI Registry 6-month follow up through 5 years. Records of health status, clinical events and biochemistry The RAI Registry Number of patients 1089 pts (on June 10th, 2015) Enrollement period March 2012 - ongoing Study centers 22 Italian sites Inclusion criteria successful implantation of 1 or more coronary BVS age <75 years patient’s informed consent After first patient is enrolled, centres are asked to enroll all BVS-treated patients consecutively for the duration of the study, with a minimun of 50. Random source verification of all data within the CRF is performed by the PI, requiring submission of the original documents covering 5% of patients in each centre. Cortese B et al. Cardiovasc Revasc Med. 2015 Sep; 16(6):340-3

Small vessel analysis - RAI-BVS All enrolled pts treated by BVS implantation in at least one small vessel, defined as pre-procedure reference vessel diameter (RVD) ≤2.5 mm at quantitative coronary analysis (QCA). 1089 consecutive patients undergoing PCI with second-generation Absorb BVS between March 2012 and June 2015 123 patients who received Absorb BVS implantation in at least one small vessel in 6 clinical sites in Italy 111 patients with treated de novo lesions 12 patients with treated restenotic lesions 2 Deaths 121 patients at median F-U of 21 months PROCEDURE: following the manufacturer and the expert consensus paper indications FOLLOW-UP: CLINICAL (visit/telephone call) ANGIOGRAPHIC (clinically driven) END-POINTS: Death, miocardial infarction, TLR, TVR TLF (cardiac death, TV-MI, TLR) Scaffold thrombosis (acute, subacute, late and very late)

PATIENTS n=123 Age (years) 61.8 ± 10.3 Male sex 95 (72.4%) Hypertension 90 (73.2%) Diabetes 30 (24.4%) Smokers Former Current 21 (17.1%) 32 (26.0%) Glomerular filtration rate 89.7 ± 31.7 Prior MI 40 (32.5%) Prior PCI 49 (39.8%) Prior CABG 7 (5.7%)

LESIONS n=123 SYNTAX score 16.8 ± 14.5 Multivessel CAD 77 (62.6%) Overall lesions/pts 1.6 ± 0.9 SVs lesions/pts 1.2 ± 0.5 Treated Vessel LMCA LAD LCX RCA 1 (0.5%) 112 (53.1%) 43 (20.4%) 56 (26.5%) (6.8%) (6.3%) (4.2%) (5.7%)

PROCEDURE Baseline TIMI flow Total scaffold lenght (9.4%) (8.3%) (7.3%) (5.7%) (3.6%) (58.9%) (76.0%) (13.0%) (39.1%) (27.6%) (37.5%) (31.8%) (10.4%) (7.8%) Baseline TIMI flow Total scaffold lenght

PROCEDURE DIiameter (mm) Lenght (mm) PATIENTS n=123 N° BVS per patient 2.0 ± 1.2 Multivessel treatment 21 (17.1%) MPS implantation 28 (22.8%) Overlap Scaffold-to-scaffold Marker-to-marker Marker-over-marker 58 12 24 Post-dilatation 115 (93.5%) Angiographic success 121 (98.4%) Procedural success 119 (96.7%) DIiameter (mm) Lenght (mm)

MEDIAN FOLLOW UP OF 21 MONTHS (IQR, 11 – 32 MONTHS) FOLLOW-UP EVENTS MEDIAN FOLLOW UP OF 21 MONTHS (IQR, 11 – 32 MONTHS) %

MEDIAN FOLLOW UP OF 21 MONTHS (INTERQUARTILE RANGE, 11 – 32 MONTHS) FOLLOW-UP EVENTS MEDIAN FOLLOW UP OF 21 MONTHS (INTERQUARTILE RANGE, 11 – 32 MONTHS) 6 months 1,6% 12 months 3,3% 21 months 5,7% CUMULATIVE INCIDENCE OF TLF TIME (DAYS) DEFINITE ST Clinical presentation Event ST type DAPT PRE-RVD BVS Pts 1 STEMI TLR + TV-MI ACUTE Yes 2.24 mm 2.5 X 18 mm Pts 2 NSTEMI LATE 2.5 mm 2.5 x 18 mm Pts 3 Stable angina TLR VERY-LATE No 2.35 mm 2.5 x 28 mm Cumulative incidence of Target Lesion Faiulure Cumulative incidence of Target Lesion Faiulure Cumulative incidence of Target Lesion Faiulure Cumulative incidence of Target Lesion Faiulure

CONCLUSIONS Patients treated by BVS for small vessel disease showed early and mid term TLF result similar to those previously reported for unselected lesions type (GHOST-EU, Absorb FIRST, Absorb EXPAND ). More analysis are needed to assess the potential role of BVS in this subset compared to large vessels or MPS.   We are waiting for the end of the enrollemnt to have more substantial results.