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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
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Conflicts of InterestConflicts of Interest
EmployeeBoston Scientific Corporation
StockholderBoston Scientific Corporation
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Boston Scientific Two-Drug StrategyBoston Scientific Two-Drug StrategyTAXUS LibertTAXUS Libertéé PROMUSPROMUS
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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
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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
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SPIRIT ISPIRIT I
SPIRIT IISPIRIT II
SPIRIT IIISPIRIT III
SPIRIT IVSPIRIT IV
SPIRIT VSPIRIT VPROMUS/XIENCE VPROMUS/XIENCE V
EverolimusEverolimus
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TAXUS & SPIRIT: TAXUS & SPIRIT: Follow-up (years)Follow-up (years)
YearsYears
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Prevalence of Diabetes MellitusPrevalence of Diabetes Mellitus
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Which DES for the Diabetic Patient?
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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)
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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
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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
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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
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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:
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-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:
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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
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Late Loss drift…Late Loss drift…
……is it clinically important?is it clinically important?
6 Months6 Months 2-5 Years2-5 Years
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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)
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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
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SIRTAX: SIRTAX: Clinical MACE 5 Years follow-upClinical MACE 5 Years follow-up
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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
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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%
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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”
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BSC Two Drug StrategyBSC Two Drug Strategy
PaclitaxelPaclitaxel
TrialCompleteN=1488
EverolimusEverolimus
TrialCompleteN=1828
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PaclitaxelPaclitaxel EverolimusEverolimus
Direct Drug comparison on the same Direct Drug comparison on the same ELEMENT PlatformELEMENT Platform
BSC Two Drug StrategyBSC Two Drug Strategy
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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
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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
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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
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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
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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
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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
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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.