Keith Dawkins MD FRCP FACC FSCAIKeith Dawkins MD FRCP FACC FSCAIChief Medical OfficerChief Medical OfficerSenior Vice PresidentSenior Vice PresidentBoston Scientific CorporationBoston Scientific Corporation

Why Boston Scientific Persists with the Two-Drug Strategy

London - January 2010London - January 2010

Conflicts of InterestConflicts of Interest

EmployeeBoston Scientific Corporation

StockholderBoston Scientific Corporation

Boston Scientific Two-Drug StrategyBoston Scientific Two-Drug StrategyTAXUS LibertTAXUS Libertéé PROMUSPROMUS

Why do Interventional Cardiologists Why do Interventional Cardiologists use a particular Stent?use a particular Stent?

SalesSales

MarketingMarketing

PerformancePerformanceDataData

CostCost

SafetySafety

HospitalityHospitality

CompetitionCompetitionCompetitionCompetition

HospitalityHospitality

HospitalHospitalAdministratorAdministrator

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 ProgramThe TAXUS Program

SPIRIT ISPIRIT I

SPIRIT IISPIRIT II

SPIRIT IIISPIRIT III

SPIRIT IVSPIRIT IV

SPIRIT VSPIRIT VPROMUS/XIENCE VPROMUS/XIENCE V

EverolimusEverolimus

TAXUS & SPIRIT: TAXUS & SPIRIT: Follow-up (years)Follow-up (years)

YearsYears

Prevalence of Diabetes MellitusPrevalence of Diabetes Mellitus

Which DES for the Diabetic Patient?

Targ

et L

esio

n Fa

ilure

(%)

TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLRTLR1 year = 365 ± 28 days 1 year = 365 ± 28 days

101/2416 81/1195

PSup=0.001

SPIRIT IV: SPIRIT IV: Primary Endpoint (TLF 1-yr)Primary Endpoint (TLF 1-yr)

Targ

et L

esio

n Fa

ilure

(%)

52/1652 49/761

P<0.001

SPIRIT IV: SPIRIT IV: Impact of Diabetes (TLF 1-yr)Impact of Diabetes (TLF 1-yr)

P=0.80

55/815 26/379

XIENCE/PROMUSXIENCE/PROMUS TAXUS ExpressTAXUS Express

TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLRTLR1 year = 365 ± 28 days 1 year = 365 ± 28 days

Targ

et L

esio

n Fa

ilure

(%)

33/562 16/199

SPIRIT IV: SPIRIT IV: Impact of Diabetes Type (TLF 1-yr)Impact of Diabetes Type (TLF 1-yr)

18/264 8/115

XIENCE/PROMUSXIENCE/PROMUS TAXUS ExpressTAXUS ExpressP=0.64 P=0.83

TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLF=Cardiac Death, Target Vessel MI, or ischemia driven TLRTLR1 year = 365 ± 28 days 1 year = 365 ± 28 days

Diabetic Restenosis: Diabetic Restenosis: the MAPK Pathwaythe MAPK Pathway

Paclitaxel

cell membrane

insulinreceptor insulin

Advanced type II diabetes

IRS1/2

mTOR

P70 S6K

cell migrationcell proliferation

PI3K Pathway

MEK

ERK1/2

InsulinResistanceMAPK Pathway

Promotes RestenosisMEK - MAPK/ERK kinaseERK – extracellular signal-related kinase

Arterioscler Thromb Vasc Biol 2006;26:1473-1480Arterioscler Thromb Vasc Biol 2006;26:1473-1480

TAXUS Trials & Registries (TLR)TAXUS Trials & Registries (TLR)DiabeticDiabetic** vs.vs. non-Diabetic, TAXUS-treated patientsnon-Diabetic, TAXUS-treated patients

**Medically Treated DiabetesMedically Treated Diabetes Published Data up to 01.2010Published Data up to 01.201011% Relative Increase in TLR for Patients with Diabetes11% Relative Increase in TLR for Patients with Diabetes

StudyStudy DMDMOddsOddsRatioRatio

UpperUpperLimitLimit

LowerLowerLimitLimit

RelativeRelativeWeightWeight Odds Ratio and 95% CIOdds Ratio and 95% CI

10214 26325 1.117 1.006 1.241CombinedEstimate:

NoNo DMDMSample SizeSample Size

TAXUS II TAXUS II 2222 238238 0.2750.275 0.0160.016 4.7224.722 0.570.57SPIRIT III 92 238 0.430 0.152 1.218 4.22TAXUS V 183 394 0.843 0.520 1.367 19.56SPIRIT IV 399 829 1.047 0.593 1.847 14.18TAXUS VI MR 39 180 1.105 0.427 2.859 5.07ATLAS SV 56 191 1.152 0.231 5.761 1.77ATLAS DS 95 165 1.172 0.495 2.773 6.17SIRTAX 93 416 1.523 0.824 2.816 12.12TAXUS IV 155 507 1.725 0.982 3.033 14.39ATLAS WH 220 650 1.918 1.166 3.155 18.48ATLAS LL 42 108 3.467 1.102 10.907 3.48

1396 3916 1.272 1.027 1.576Ontario 835 1219 1.033 0.772 1.383 16.98ARRIVE 2 1437 3568 1.043 0.830 1.310 27.65ARRIVE 1 675 1812 1.082 0.787 1.487 14.22OLYMPIA III 3160 9287 1.103 0.878 1.387 27.52OLYMPIA II 2711 6523 1.113 0.804 1.541 13.63

8818 22409 1.073 0.951 1.209

Favours DiabetesFavours Diabetes Favours No DiabetesFavours No Diabetes

TRIALS:

REGISTRIES:

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

*TLR not reported; TVR rates were used. Published Data up to 01.2010Published Data up to 01.2010

StudyStudy DMDMOddsOddsRatioRatio

UpperUpperLimitLimit

LowerLowerLimitLimit

RelativeRelativeWeightWeight Odds Ratio and 95% CIOdds Ratio and 95% CI

Favours Diabetes Favours Non-Diabetes

49% Relative Increase in TLR for Patients with Diabetes

NoNo DMDMSample SizeSample Size

**

6464 13857 1.329 1.676CombinedEstimate: 1.492

***

SIRTAX 108 395 0.932 0.415 2.090SPIRIT III 198 471 0.942 0.449 1.979ENDEAVOR I-III 293 1004 1.308 0.779 2.196SIRIUS 131 402 1.826 0.987 3.376SPIRIT IV 786 1669 2.392 1.448 3.950ARTS II 159 448 2.668 1.496 4.758PORTO I & II 114 150 6.519 0.308 138.015

1789 4539 1.707 1.337 2.179ELISIR 582 1605 1.244 0.862 1.797German CYPHER 1948 4707 1.252 1.042 1.505Ontario Registry 835 1219 1.607 1.205 2.144Berenguer, 2006 98 133 1.645 0.488 5.539EVASTENT 844 887 1.804 1.130 2.881Kumar, 2007 297 541 2.894 1.587 5.277Hoffman, 2007 71 226 8.288 1.585 43.343

4675 9318 1.435 1.258 1.637

9.1310.8222.1815.7723.6717.790.64

12.8751.5720.981.187.944.820.64

TRIALS:

REGISTRIES:

TAXUS IV: 5-yr Clinical ResultsTAXUS IV: 5-yr Clinical ResultsPa

tient

s (%

)

Diabetesn=163

Diabetesn=152

No Diabetesn=480

No Diabetesn=499

BMSBMS TAXUS ExpressTAXUS Express

J Am Coll Cardiol Intv 2009;2:1248-1259J Am Coll Cardiol Intv 2009;2:1248-1259

Late Loss drift…Late Loss drift…

……is it clinically important?is it clinically important?

6 Months6 Months 2-5 Years2-5 Years

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

6 Months6 Months 2 Years2 Years

Xience/PromusXience/PromusTAXUS*

Xience/Promus TAXUS+

Xience/Promus: 0.17 ± 0.32 (n=97)Xience/Promus: 0.17 ± 0.32 (n=97)TAXUS: 0.33 ± 0.32 (n=35)TAXUS: 0.33 ± 0.32 (n=35)

P=0.0037P=0.0037

Xience/Promus: 0.33 ± 0.37 (n=97)Xience/Promus: 0.33 ± 0.37 (n=97)TAXUS: 0.34 ± 0.34 (n=35)TAXUS: 0.34 ± 0.34 (n=35)

P=0.6026P=0.6026

0

20

40

60

80

100

-0.75 -0.5 -0.25 0 0.25 0.5 0.75 1 1.25 1.5 1.75 2In-stent Late Loss (mm)In-stent Late Loss (mm)

% o

f Les

ions

0

20

40

60

80

100

-0.75 -0.5 -0.25 0 0.25 0.5 0.75 1 1.25 1.5 1.75 2

In-stent Late Loss (mm)In-stent Late Loss (mm)

SIRTAX: SIRTAX: 8 months 8 months vs.vs. 5 years QCA follow-up 5 years QCA follow-upIn

-Ste

nt L

ate

Loss

(mm

)In

-Ste

nt L

ate

Loss

(mm

)

ΔΔ 0.18mm 0.18mm ΔΔ 0.12mm 0.12mm

P8months<0.001

P5years=0.21

SIRTAX: SIRTAX: Clinical MACE 5 Years follow-upClinical MACE 5 Years follow-up

TAXUS IITAXUS II: Late Loss Stability over Time: Late Loss Stability over TimeIn

-Ste

nt L

ate

Loss

(mm

) In

-Ste

nt L

ate

Loss

(mm

)

Am J Cardiol 2007;99:607-615Am J Cardiol 2007;99:607-615

P=0.1669

Is the BSC Two-Drug Strategy Working?Is the BSC Two-Drug Strategy Working?

Source: MRG, BSJ, BSC Internal Data (December 2009)Source: MRG, BSJ, BSC Internal Data (December 2009)

DES

Mar

ket S

hare

(%)

DES

Mar

ket S

hare

(%)

48%48% 46%46% 45%45%

Element Stent PlatformElement Stent PlatformGeometry designed for drug delivery

Four stent modelsConsistent surface-to-artery ratios

Apex™ balloonBi-component balloonMultilayer

Platinum Chromium AlloyThin strutsRadio-opaqueLow recoilHigh radial strength

Express 0.0052” Liberté 0.0038” Driver 0.0036” Element 0.0032”Vision 0.0032”Cypher 0.0055”

BSC Two Drug StrategyBSC Two Drug Strategy

PaclitaxelPaclitaxel

TrialCompleteN=1488

EverolimusEverolimus

TrialCompleteN=1828

PaclitaxelPaclitaxel EverolimusEverolimus

Direct Drug comparison on the same Direct Drug comparison on the same ELEMENT PlatformELEMENT Platform

BSC Two Drug StrategyBSC Two Drug Strategy

Next Generation DES AttributesNext Generation DES Attributes

SafetyNo Stent Thrombosis (‘BMS’ like)Shortened/No DAPT Requirement

EfficacyLow Late Loss, Binary RestenosisLow TLR, Low Clinical Symptom Recurrence

Lowering the Requirement for Lowering the Requirement for DAPT?DAPT?

Reduced Polymer LoadAblumenal PolymerBioerodable PolymerNo Polymer

Reduced Drug LoadStent Delivery System

Stent MaterialThinner StrutsModified Stent GeometrySurface Coating

JACTAX HD Results JACTAX HD Results vs.vs. ATLAS Matched (9 months)ATLAS Matched (9 months)

TaxusTaxusLibertéLiberté(n=215)(n=215)

TaxusTaxusLibertéLiberté(n=215)(n=215)

LabcoatLabcoatLibertéLiberté(n=97)(n=97)

LabcoatLabcoatLibertéLiberté(n=97)(n=97)

Late

Los

s (m

m)

In-Stent In-Segment

p=0.23 p=0.17

J Am Coll Cardiol Intv 2010. In PressJ Am Coll Cardiol Intv 2010. In Press

Labcoat Relative Polymer Labcoat Relative Polymer ThicknessThickness

LABCOATPolymer(Thickness)

E. Coli(Length)

Red Cell(Diameter)

T. LibertéPolymer(Thickness)

Neutrophil(Diameter)

Micr

on (µ

)

LABCOAT = Minimal Drug + Ultrathin Bioerodable Abluminal PolymerLABCOAT = Minimal Drug + Ultrathin Bioerodable Abluminal Polymer

Relative Drug Coating WeightsRelative Drug Coating Weights

0 50 100 150 200 250 300 350 500 685 1267l l l l l l l l l l l

Bare

Met

alBa

re M

etal

Coating Weight (µg, 16mm Stent)Coating Weight (µg, 16mm Stent)

//// //

10µg10µg 20µg20µg

PaclitaxelPaclitaxel

TrialComplete

N=103

BSC Two Drug StrategyBSC Two Drug Strategy

EverolimusEverolimus

Next Generation DESNext Generation DESLow Drug Dose, Ablumenal Delivery, Bioerodable Low Drug Dose, Ablumenal Delivery, Bioerodable

Polymer Short DAPTPolymer Short DAPT??

Trial to commenceQ2 2010

Conclusions: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.