Why I Don’t Believe in BRS as the Future Scaffold Technology Keith Dawkins MD FRCP FACC FSCAI Global Chief Medical Officer Executive Vice President Boston Scientific Corporation

Conflict of Interest Boston Scientific Corporation Employee Stockholder

The BRS Story Now that you have that new very expensive disappearing stent that you can’t see, I assume that you have no more chest pain Mr. Jones…?

Is BRS a stairway to Heaven… …or will it remain a niche product?

The BRS Story…. …nothing left behind, a laudable goal

BRS Share Determines Investment Thesis Niche  Pass Workhorse  Invest $1.5B OR 10% 40% Source: Eucomed (FY 2014 – Estimate) FRS Share (%)

The BRS Story so far… Thrombosis Rigid Fracture Malapposition Recoil Low Radial Strength Poor Visualization Thrombosis Malapposition Infarction Fracture Displacement Death Restenosis Recoil Thick GHOST Migration Cost Rigid Pain? Chest Lesion Preparation Limited Matrix Particulates Where there's hope, there's life… Anne Frank: The Diary of a Young Girl

BVS: Novel Concept, First Generation Technology CYPHER® CE-Mark April 15, 2002 BVS CE-Mark January 1, 2011 Strut Thickness 152.6µm2 (inc. polymer) Strut Thickness 157µm x 200µm PLLA SYNERGY

Malapposition, dislodgement, fracture, thrombosis Are First generation Fully Bioerodable Stents Fit For Purpose…? Malapposition, dislodgement, fracture, thrombosis

BVS: Stent Thrombosis (GHOST Registry) 1189 patient single arm, ‘Real World’ registry of the ABSORB BVS at 10 European Centers Low Complexity (SYNTAX Score = 11.3 ±7.9; A/B1 = 48.8%) Annualized TLF = 10.1% Annualized Definite/Probable ST = 3.4% Capoddano D: EuroInterv 2014:10-online publish-ahead-of-print

Real-World BVS ST Rates STUDY PATIENTS ST RATE Jaguszewski*** 106 2.1% Mainz 150 2.7% RAI Registry* 74 AMC Registry*** 135 3.0% GHOST Registry 1189 3.4%** *STEMI Population, **Annualized Rate, ***Def ST Only GHOST: Capodanno, et al. EuroIntervention 2014; Mainz: Gori, et al. EuroIntervention 2013; RAI: lelasi, A. EuroPCR 2014; AMC Registry: Kraak, et al. Eurointervention2014; Jaguszewski, et al. Clin Res Cardiol 2014. Results from different studies are not directly comparable. Information provided for educational purposes only.

All-Comers Populations ST Rates: EES & BVS BVS All-Comers Populations XIENCE CoCr EES PROMUS PtCr EES ABSORB BVS ABSORB BVS (6-months) 3.4 BVS Selected Populations Ghost AMC RAI Mainz Expand Jaguszewski EXTEND ABSORB II Cohort B HOST ASSURE PE-PROVE DUTCH PEERS PLATINUM + TWENTE COMPARE EXAMINATION 2.1 All-Comers Populations N= 751 897 694 987 1862 905 1101 2503 101 335 660 106 171 150 74 135 1189

Proposed Algorithm for the Treatment of Early Scaffold Thrombosis Tamburino C: EuroIntervention 2015;10-online publish-ahead-of-print January 2015

Possible Causes of High ST Rates with BVS Poor lesion Preparation Thick Struts Non-laminar Flow Geographic Miss Edge Dissection Inadequate Post-Dilatation Malapposition Delayed Healing Fracture

Not All Fractures are Visible on OCT BVS Fracture is Common Not All Fractures are Visible on OCT

Premature low-pressure BVS Fracture compared with Elixir DESolve & Xience Xpedition Ormiston JA: EuroIntervention 2015;10-online publish-ahead-of-print February 2015

Post-dilatation balloon diameter & percentage of 3 Post-dilatation balloon diameter & percentage of 3.0 mm diameter devices with strut fracture Ormiston JA: EuroIntervention 2015;10-online publish-ahead-of-print February 2015

Bioresorbable Drug-Eluting Stents An Immature Technology in Need of Mature Application 1.5 - 1.0 - 0.5 - 0.0 - Stent Thrombosis (%)* *Rates refer to pooled data analysis on adjudicated definite stent thrombosis from published registries with more than 100 treated patients, the ABSORB-II randomized trial, the BVS EXAMINATION study, and EVOLVE II Byrne RA: JACC Interv 2015;8:198-200 Kereiakes DJ: Circ Cardiovasc Interv 2015 (submitted)

ABSORB-II: Interim 1-year Analysis Co-Primary End-points: Vasomotion (change in mean lumen diameter before and after nitrate administration at 3 years) Difference between minimum lumen diameter (after nitrate administration) after the index procedure and at 3 years Serruys PW: Lancet 2015;385:43-54

ABSORB-II: Interim 1-year Analysis Seattle Angina Questionnaire (SAQ) No significant difference in angina between ABSORB BVS and XIENCE Unvalidated post hoc analysis. Time to first occurrence and duration. 8.7% difference in favor of BVS, p=0.04 Serruys PW: Lancet 2015;385:43-54

BSC is Interested in the Space FAST Program Expanded (3.0x16 mm) FRS Distribution Agreement Equity Position

Conclusions ‘Nothing left behind’ is conceptually appealing both to patients and their physicians BVS acute performance is suboptimal BVS has been advocated to a broad patient population, with a paucity of robust clinical supportive data Complications associated with BVS preclude its use as a workhorse product The ultimate role of Bioresorbable Scaffolds in everyday clinical practice remains uncertain