Keith Dawkins MD FRCP FACC FSCAI Chief Medical Officer Senior Vice President Boston Scientific Corporation Why Boston Scientific Persists with the Two-Drug Strategy London - January 2010

Conflicts of Interest Employee Boston Scientific Corporation Stockholder Boston Scientific Corporation

Boston Scientific Two-Drug Strategy TAXUS Liberté PROMUS

Why do Interventional Cardiologists use a particular Stent? Sales Marketing Performance Data Cost Safety Hospitality Competition Competition Hospitality HospitalAdministrator

6 Platforms 18 Pre-Market and 11 Post-Market studies 9,138 IDE Patients with 90,560 Patient-Years of F/U 37,498 PMS Patients with 52,680 Patient-Years of F/U 46,636 TAXUS patients with 143,240 Patient-Years of F/U The TAXUS Program

SPIRIT I SPIRIT II SPIRIT III SPIRIT IV SPIRIT V PROMUS/XIENCE V Everolimus

TAXUS & SPIRIT: Follow-up (years) Years

Prevalence of Diabetes Mellitus

Which DES for the Diabetic Patient?

Target Lesion Failure (%) TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLR 1 year = 365 ± 28 days 101/ /1195 P Sup =0.001 SPIRIT IV: Primary Endpoint (TLF 1-yr)

Target Lesion Failure (%) 52/ /761 P<0.001 SPIRIT IV: Impact of Diabetes (TLF 1-yr) P= /815 26/379XIENCE/PROMUS TAXUS Express TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLR 1 year = 365 ± 28 days

Target Lesion Failure (%) 33/562 16/199 SPIRIT IV: Impact of Diabetes Type (TLF 1-yr) 18/264 8/115XIENCE/PROMUS TAXUS Express P=0.64P=0.83 TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLR 1 year = 365 ± 28 days

Diabetic Restenosis: the MAPK Pathway Paclitaxel cell membrane insulin receptor insulin Advanced type II diabetes IRS1/2 mTOR P70 S6K cell migration cell proliferation PI3K Pathway MEK ERK1/2 Insulin Resistance MAPK Pathway Promotes Restenosis MEK- MAPK/ERK kinase ERK – extracellular signal-related kinase Arterioscler Thromb Vasc Biol 2006;26:

TAXUS Trials & Registries (TLR) Diabetic * vs. non-Diabetic, TAXUS-treated patients * Medically Treated Diabetes Published Data up to

-Olimus Trials & Registries (TLR) Diabetic vs. Non-Diabetic, -Olimus-treated patients

TAXUS IV: 5-yr Clinical Results Patients (%) Diabetes n=163 Diabetes n=152 No Diabetes n=480 No Diabetes n=499 BMS TAXUS Express J Am Coll Cardiol Intv 2009;2:

Late Loss drift… …is it clinically important? 6 Months 2-5 Years

SPIRIT II : In-Stent Late Loss 6 months vs. 2 Years

SIRTAX: 8 months vs. 5 years QCA follow-up In-Stent Late Loss (mm) Δ 0.18mm Δ 0.12mm P 8months <0.001 P 5years =0.21

SIRTAX: Clinical MACE 5 Years follow-up

TAXUS II : Late Loss Stability over Time In-Stent Late Loss (mm) Am J Cardiol 2007;99: P=0.1669

Is the BSC Two-Drug Strategy Working? Source: MRG, BSJ, BSC Internal Data (December 2009) DES Market Share (%) 48% 46% 45%

Element Stent Platform Geometry designed for drug delivery Four stent models Consistent surface-to-artery ratios Apex ™ balloon Bi-component balloon Multilayer Platinum Chromium Alloy Thin struts Radio-opaque Low recoil High radial strength Express ” Liberté ” Driver ” Element ” Vision ” Cypher ”

BSC Two Drug Strategy Paclitaxel Element Stent Trial Complete N=1488 Everolimus Element Stent Trial Complete N=1828

PaclitaxelEverolimus Element Stent Direct Drug comparison on the same ELEMENT Platform BSC Two Drug Strategy

Next Generation DES Attributes Safety No Stent Thrombosis (‘BMS’ like) Shortened/No DAPT Requirement Efficacy Low Late Loss, Binary Restenosis Low TLR, Low Clinical Symptom Recurrence

Lowering the Requirement for DAPT? Reduced Polymer Load Ablumenal Polymer Bioerodable Polymer No Polymer Reduced Drug Load Stent Delivery System Stent Material Thinner Struts Modified Stent Geometry Surface Coating

JACTAX HD Results vs. ATLAS Matched (9 months) TaxusLiberté(n=215) TaxusLiberté(n=215) LabcoatLiberté(n=97) LabcoatLiberté(n=97) Late Loss (mm) In-StentIn-Segment p=0.23 p=0.17 J Am Coll Cardiol Intv In Press

Labcoat Relative Polymer Thickness LABCOAT Polymer (Thickness) E. Coli (Length) Red Cell (Diameter) T. Liberté Polymer (Thickness) Neutrophil (Diameter) Micron (µ) LABCOAT = Minimal Drug + Ultrathin Bioerodable Abluminal Polymer

Relative Drug Coating Weights l l l l l l l l l l l Bare Metal Jactax LD Jactax HD BioMatrix Promus T. Liberté Coating Weight (µg, 16mm Stent) // 10µg20µg Nevo

Paclitaxel Labcoat Liberté Trial Complete N=103 BSC Two Drug Strategy Labcoat Element Everolimus Next Generation DES Low Drug Dose, Ablumenal Delivery, Bioerodable Polymer Short DAPT ? EVOLUTION Trial to commence Q2 2010

Conclusions: Nine years of clinical data attest to the safety and efficacy of TAXUS stents. Differences in outcome between Diabetic and Non-Diabetic patients based on the MOA is real, favouring Paclitaxel as the drug of choice. Late Loss drift associated with –olimus eluting stents remains an unresolved issue of possible clinical significance. The Two-Drug strategy affords dominant market share. BSC continues to assess the roles of a Two-Drug strategy in the DES pipeline.