taxus atlas sv and ll 9mtct october 22, 2007, 1pm late breaking trial the taxus liberté 2.25 and...

TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking TrialThe TAXUS Liberté 2.25 and 38mm stents are limited by US federal law to investigational use

TAXUS ATLAS SMALL VESSEL and LONG LESION

First Report of Nine-Month Clinical and Angiographic Results

Mark A. Turco, MD, FACC

and

John A. Ormiston, MBChBOn behalf of the TAXUS ATLAS Investigators

TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial

Conflict of Interest Disclosures

TAXUS ATLAS SV and LL and production of this presentation were supported by Boston Scientific Corporation (BSC)

The following relationships exist related to BSC and this presentation:

Mark A. Turco: • Research grants and other research support• Consultant• Member of speaker’s bureau

John A. Ormiston: • Research grants and other research support• Consultant• Member of advisory board


TAXUS ATLAS Small Vessel and Long Lesion Study Enrollers

Investigator Institution SV PatientsEnrolled

LL PatientsEnrolled

J. Hall St. Vincent’s Hospital, Indianapolis, IN 25 15T. Mann WakeMed, Raleigh, NC 24 12L. Cannon Northern Michigan Hospital, Petoskey, MI 18 17G. Mishkel St. John’s Hospital, Springfield, IL 25 5M. Webster Auckland City Hospital, Auckland, New Zealand 8 22C. O’Shaughnessy Elyria Memorial Hospital, Elyria, OH 12 14T. McGarry Oklahoma Heart Hospital, Oklahoma City, OK 18 4G. Stone Columbia University Medical Center, NY, NY 16 4S. Yakubov Riverside Methodist Hospital, Columbus, OH 11 5I. Gilchrist Milton S. Hershey Medical Ctr., Hershey, PA 12 3M. Lucca St. Mary’s Duluth Clinic Reg Heart Ctr., Duluth, MN 6 9B. Armstrong Wellmont Holston Valley Medical Ctr., Kingsport, TN 9 5A. Raizner Methodist DeBakey Hospital, Houston, TX 11 2M. Kellett Maine Medical Center, Portland, ME 10 2A. Taussig Florida Hospital, Orlando, FL 9 3M. Turco Washington Adventist Hospital, Takoma Park, MD 9 3J. Kozina Mercy General Hospital, Sacramento, CA 8 3B. Bertolet North Mississippi Medical Center, Tupelo, MS 5 6C. Chan National Heart Centre, Singapore, Singapore 8 2J. Hopkins Christiana Hospital, Newark, DE 7 2G. Wilkins Dunedin Hospital, Dunedin, New Zealand 5 4D. McClean Christchurch Hospital, Christchurch, New Zealand 4 4H. Cheem Tan National University Hospital, Singapore, Singapore 1 3D. S. Gantt Scott & White Hospital, Temple, TX 0 1


Study OrganizationTAXUS ATLAS Small Vessel and Long Lesion

Principal Investigators Mark A. Turco, MDJohn A. Ormiston, MBChB

Executive Committee Mark A. Turco, MDJohn A. Ormiston, MBChBLaura BrentonLazar Mandinov, MD, PhDJoerg Koglin, MD, PhD

Data Management & Analysis Boston Scientific, Natick, MA

Site Monitoring Boston Scientific, Natick, MAAPEX International, Taipei, Taiwan

Core Angiographic Laboratory Jeffrey Popma, MD Brigham & Women’s Hospital Boston, MA

Core IVUS Laboratory(ATLAS Long Lesion Only)

Neil Weissman, MDMedStar, Washington, DC

Clinical Events Committee Don Cutlip, MD (Chair); Julian Aroesty, MD; Manish Chauhan, MD; Germano DiSciascio, MD; Kalon K. L. Ho, MD; Joseph P. Kannam, MD; Michel Vandormael, MD

Data Monitoring Committee W. Douglas Weaver, MD (Chair); David P. Faxon, MD; Kirk Garrett, MD; David Moliterno, MD; Jan Tijssen, MD; Adam Greenbaum, MD


TAXUS Express to TAXUS Liberté Evolution of the TAXUS Technology

Design Improvements in TAXUS Liberté Improved performance

27% reduced stent strut thickness

Reduced stent to artery ratio

More homogeneous drug distribution

15% more conformable and 15% more flexible

5 wing fold balloon: improved re-wrap and less withdrawal resistance

TAXUS ATLAS program: Transfer of proven drug/polymerTAXUS technology to the improved Liberté platform

TAXUS LibertéTAXUS Express


Liberté Patients

TAXUS ATLAS Workhorse

N=871

TAXUS ATLAS Direct Stent

N=247

TAXUS ATLASSmall Vessel

N=261

TAXUS ATLASLong Lesion

N=150

9m 1o

Endpoint TVR % DS % Diameter Stenosis (Analysis Segment)

Control TAXUS Express

TAXUS Liberté Workhorse;

QCA subgroup

TAXUS Express and

BMS(TAXUS V)

TAXUS Express

(TAXUS IV & V)

RVD 2.5 – 4.0 mm ≥2.2-<2.5 mm ≥2.7-≤4.0 mm

Lesion Length 10 – 28 mm 10 – 28 mm 26 – 34 mm

Multiple Stenting No No No

TAXUS ATLAS ProgramEvaluating the TAXUS Liberté Stent

Global, Multi-center, Historically Controlled Trials on De Novo Lesions


TAXUS LibertéTAXUS ATLAS Expansion Program

Non-Inferiority

TAXUSExpress

BMSExpress

Superiority Non-Inferiority

TAXUSExpress

TAXUS LibertéLong (38 mm)



TAXUSLiberté 2.25 mm

Small Vessel


TAXUS ATLAS Small VesselStudy Flow

Intent-to-Treat

TAXUS Express N=75

TAXUS Liberté 2.25N=261

Express (BMS)N=155

DES ControlBMS Control

TAXUS V pts with:• RVD≤2.5mm, lesions≤28mm• Single planned 2.5 or

2.25mm study stent9-Month Follow-Up

TAXUS ExpressN=72 (96%)

TAXUS Liberté 2.25N=257 (98%)

Express (BMS)N=148 (95%)

9-Month QCA Follow-Up

TAXUS ExpressN=55 (73%)

TAXUS Liberté 2.25N=212 (81%)

Express (BMS)N=105 (68%)

TAXUS V pts with:• RVD≤2.5mm, lesions≤28mm• Single planned 2.25mm

study stent

Small Vessel


Baseline Characteristics for Small VesselTAXUS Liberté 2.25 versus BMS Control

*QCA Data

BMSControlN=155

T. Liberté2.25 mmN=261

P-value

Age (years) 64.2±10.9 63.4±11.1 0.45

Male (%) 60.0 56.3 0.46

Diabetes (%) 36.8 36.4 0.94

Hyperlipidemia (%) 79.4 82.0 0.51

Hypertension (%) 78.7 76.6 0.62

RVD (mm)* 2.20±0.34 2.02±0.30 <0.0001

%DS* 72.1±10.7 67.3±10.9 <0.0001

Lesion length (mm)* 14.3±6.3 14.5±6.9 0.71

B2 / C lesions (%) 79.4 69.0 0.0213

Small Vessel


Primary Endpoint Met for Small VesselTAXUS Liberté 2.25 Superior to BMS Control

0

10

20

30

40

50

60

70

% D

iam

ete

r S

teno

sis P<0.0001

45.6±23.5

32.1±18.4

% DS (Analysis Segment)Primary Endpoint

BMS Control (N=155) TAXUS Liberté 2.25 (N=261)

0

1

2

In-Stent In-Segment

P<0.0001 P<0.0001

0.84±0.57

0.28±0.45

0.55±0.55

0.16±0.40

Late Loss

Small Vessel


9-Month Clinical Events in Small VesselSignificant TAXUS Liberté Clinical Benefit vs. BMS

0.72.6

17.6

5.9

19.621.6

0.82.7

5.8 6.6

10.1

12.8

CardiacDeath

OverallMACE

OverallMI

Pa

tient

s (%

)

TVR Remote

TLR

P=1.00 P=1.00 P=0.0065 P=0.0191P=0.0001 P=0.78

41%48%

67%

OverallTVR

0

5

10

15

20

25

30

AllDeath

P=1.00

0.7 1.2

BMS Control (N=155) TAXUS Liberté 2.25 (N=261)



Non-Inferiority

TAXUSExpress

BMSExpress


TAXUSExpress





SuperiorityMet

Small Vessel


Baseline Characteristics in Small VesselTAXUS Liberté 2.25 versus DES Control

*QCA Data

T. ExpressDES Control

N=75

T. Liberté2.25

N=261P-value

Age (years) 64.7±9.4 63.4±11.1 0.36

Male (%) 66.7 56.3 0.11

Diabetes (%) 44.0 36.4 0.23

Smoker (%) 70.7 58.2 0.05


Hypertension (%) 81.3 76.6 0.39

RVD (mm) 2.03±0.31 2.02±0.30 0.77

%DS 70.0±10.6 67.3±10.9 0.0581

Lesion length (mm) 11.8±5.7 14.5±6.9 0.0025

MLD (mm) 0.60±0.23 0.66±0.24 0.08

B2 / C lesions (%) 58.1 69.0 0.08

Small Vessel


Primary Endpoint Met for Small Vessel T. Liberté 2.25 non-inferior (superior) to T. Express

Non-inferiority met in ITT population (P<0.0001)

% Diameter Stenosis (Analysis Segment): ITT Population

0 5% 10%-10% -5%

Pre-specifiedMargin

10.0%

Non-inferiority also demonstrated in per protocol population (P<0.0001)

95% CI is less than prespecified margin

Difference-6.3%

95%Confidence

Interval -1.4%

P<0.0001 for Non-inferiority

Difference (T. Liberté – T. Express)T. Express

ControlT. Liberté

2.25

% D

iam

ete

r S

teno

sis

T. Liberté 2.25 is Superior to T. Express Control (ITT population)

P=0.0351 for Superiority

38.4±23.6 32.1

±18.4

Small Vessel


9-Month QCA Outcomes in Small VesselSignificant benefit for TAXUS Liberté 2.25

0

1

2.2

25.9

32.7

3.94.5

13.018.5

3.4

0

10

20

30

40

50

60

ProximalEdge

In-Stent

P=0.02

Paired lesion analysis

Binary Restenosis (% pts) Late Loss (mm)

In-Stent Analysis Segment

P=0.03 P=0.0085

0.44±0.61

0.28±0.45

0.33±0.52

0.16±0.40

P=0.69 P=1.00

DistalEdge

P=0.02

T. Express Control (N=75) T. Liberté 2.25 (N=261)

Small Vessel


9-Month Clinical Events in Small VesselSignificant Clinical Benefit for TAXUS Liberté

2.74.1

13.7

6.8

17.8

20.5

0.82.7

5.8 6.6

10.112.8

CardiacDeath

OverallMACE

OverallMI

Pa

tient

s (%

)

TVR Remote

TLR

P=0.21 P=0.46 P=0.07 P=0.10P=0.024 P=1.00

38%43%

58%

OverallTVR

0

5

10

15

20

25

30

AllDeath

P=0.30

2.71.2

T. Express Control (N=75) T. Liberté 2.25 (N=261)

Small Vessel


Stent Thrombosis (Per Protocol) in SVSimilar Rates for all 3 Arms

1.4

0.00.00.4

1.3

0.00

1

2

3

4

5

(n=2)

% S

T (

per

pro

toco

l)

0.22 1.00

(n=1)

Rates were identical using ARC Definite/Probable Definition

0 – 30 days 31 – 284 days

Acute &Subacute Late

1.4

0.4

1.3

0

1

2

3

4

5

Total ST

0.39

(n=2) (n=1)

0 – 284 days

0.14 1.00 0.56

T. Express Control (N=75) T. Liberté 2.25 (N=261) BMS Control (N=155)

(n=2) (n=2)

P= P=

Small Vessel


TAXUS ATLAS Small Vessel Summary

Efficacy Outcomes:

Primary endpoint of 9-month % DS (analysis segment) was met:

• TAXUS Liberté 2.25 is superior to Express BMS Control

• TAXUS Liberté 2.25 is non-inferior (and actually superior) to

TAXUS Express Control

Significant reductions in Late Loss and Restenosis with TAXUS

Liberté vs. both TAXUS Express and BMS

Significantly reduced TLR in TAXUS Liberté vs. both Controls

Safety Outcomes:

Rates for death, cardiac death, MI, and stent thrombosis for the

TAXUS Liberté 2.25 group low and comparable to TAXUS

Express and BMS



Non-Inferiority

TAXUSExpress

BMSExpress


TAXUSExpress





SuperiorityMet

Non-InferiorityMet

Long Lesion


TAXUS ATLAS Long LesionStudy Flow

Intent-to-Treat

9-Month Follow-Up

9-Month QCA Follow-Up

TAXUS Express N=145

T. Express Control T. Liberté 38mm

TAXUS Liberté N=150

TAXUS Express N=138 (95.2%)

TAXUS Express N=91 (62.8%)

TAXUS Liberté N=145 (96.7%)

TAXUS Liberté N=126 (84.0%)

TAXUS IV and V pts with:• RVD≥2.5 - ≤4.0mm• Lesions ≥26 - ≤34 mm

Long Lesion


Baseline Characteristics in Long LesionTAXUS Liberté used in Complex Populations

* QCA Data

T. ExpressControlN=145

T. Liberté38 mmN=150

P-value

Age (years) 62.3±12.0 63.3±10.2 0.45

Male (%) 68.3 73.3 0.34

Diabetes (%) 29.0 28.0 0.85

Smoker (%) 62.8 71.3 0.12


Hypertension (%) 71.7 76.0 0.40

RVD (mm) 2.76±0.49 2.80±0.42 0.49

%DS 66.5±10.9 67.0±11.0 0.65

Lesion length (mm) 21.6±7.3 28.1±8.3 <0.0001

MLD (mm) 0.93±0.36 0.92±0.34 0.88

B2 / C lesions (%) 89.4 98.7 0.0008

Long Lesion


Procedural Characteristics

* QCA Data

T. ExpressControlN=145

T. Liberté38 mmN=150

P-value

Clinical Procedural Success 96.3 100.0 0.0431

Procedure time (min) 52.4±24.0 52.6±32.4 0.96

No Non-Target Lesion Tx 49.4±23.3 43.0±19.5 0.0313

Total Stented Length (mm) 32.3±5.5 37.8±4.8 <0.0001

Stent:Lesion Length Ratio* 1.68±0.71 1.47±0.57 0.0068

Multiple Stents (%) 53.8 16.0 <0.0001

Max. Pressure (atm) 15.5±2.6 16.7±3.7 0.0007

Post-Dilation (%) 58.6 53.3 0.36

Unplanned stenting (%) 9.0 16.7 0.048

Long Lesion


Primary Endpoint Met for Long Lesion TAXUS Liberté Non-inferior to TAXUS Express

T. Express Control

T. Liberté 38 mm

An

alys

is S

egm

ent

% D

S

Non-inferiority (P=0.001)T. Liberté 38 mm is similar to T. Express Control

Difference-0.93

95% CI3.19

Pre-specifiedMargin

6.89%

32.6±19.3

31.7±17.2

-1% 0 1% 2% 3% 4% 5% 6% 7%

Difference (T. Liberté – T. Express)

% Diameter Stenosis (Analysis Segment): ITT Population

Non-inferiority also met in per protocol population (P=0.001) and after propensity adjustment (P<0.0001)

P=0.71

95% CI is less than prespecified margin

Non-inferiority met

Long Lesion


9-Month Clinical Events for Long LesionSignificantly Reduced MI Compared to T. Express

T. Express Control (N=145) T. Liberté 38 mm (N=150)

2.8

6.3 7.0

1.4

8.5

14.8

0.01.3

6.0

3.4

8.7 9.4

CardiacDeath

OverallMACE

OverallMI

Pa

tient

s (%

)

TVR Remote

TLR

P=0.06 P=0.026 P=0.93 P=0.16P=0.73 P=0.45

OverallTVR

0

2

4

6

8

10

12

14

16

18

20

AllDeath

P=0.21

2.8

0.7

79%

Long Lesion


NQMI(n=7)

NQMI(n=2)

QMI(n=2)

Breakdown of MI EventsReduced In-Hospital Non-Q MI in TAXUS Liberté

Non-Q-Wave MI

CK-MB≥5x(n=1)

CK-MB≥5x(n=2)

0

2

4

6

8

0.0%

4.1%

CK-MB≤3(n=3)

P=0.013

CK-MB≥5x(n=3)

P=1.00

In-Hospital Discharge – 9m

TAXUSExpress

TAXUSLiberté

TAXUSExpress

TAXUSLiberté

Pa

tient

s (%

)

Long Lesion


3.90.0

0

5

10

15

20

25

Breakdown of MI EventsSingle vs. Multiple Stents

9.1

1.60

5

10

15

20

25

P=0.0213

SINGLE STENT

(n=6 ) (n=2)

Pa

tient

s (%

)

MULTIPLE STENTS

P=1.00

(n=3) (n=0)

TAXUSExpress(N=67)

TAXUSLiberté

(N=126)

TAXUSExpress(N=78)

TAXUSLiberté(N=24)

Long Lesion


Stent Thrombosis to 9 MonthsNo ST Events with TAXUS Liberté

*Academic Research Consortium

0.00.7

0.0 0.00

1

2

3

4

5

P=0.49

(n=1)

Acute, Subacute(0-30 Days)

Late(31-284 Days)

0.70.0

0

1

2

3

4

5

Total ST(0-284 days)

P=0.49

T. Express Control (N=75) T. Liberté 38mm (N=150)

(n=1)Patients (%)

ProtocolDefinition

Patients (%)

ARC*Def/Prob

0.0

1.4

0.0 0.00

1

2

3

4

5

P=0.24

(n=2)

1.4

0.00

1

2

3

4

5

P=0.24

(n=2)

Long Lesion


TAXUS ATLAS Long Lesion Summary

Efficacy Outcomes:

Primary endpoint of 9-month % DS (analysis segment) was met:

• T. Liberté 38 mm non-inferior to T. Express Control

Safety Outcomes:

No cardiac death or stent thrombosis in TAXUS Liberté

Significantly reduced myocardial infarction rate in TAXUS Liberté

compared to TAXUS Express, even in single stents

Procedural Observations:

Reduced procedural time and increased procedural success rate

compared to TAXUS Express


TAXUS ATLAS SV and LLOverall Summary

Clinical Benefits:SAFETY: Maintained or improved

Similarly low death, MI and ST rates for TAXUS Liberté 2.25mm compared to TAXUS ExpressSignificantly reduced MI for TAXUS Liberté Long (38mm) compared to TAXUS Express, with comparable death and ST

RESTENOSIS: ReducedLate Loss, Binary Restenosis Reduced:

• In TAXUS Liberté 2.25 mm compared to both BMS and TAXUS Express

TLR Reduced: In T. Liberté 2.25 compared to BMS and T. Express

DELIVERABILITY: EnhancedDesign improvements in TAXUS Liberté platform vs. TAXUS ExpressReduced procedure time

Primary endpoint met in both studies


Conclusions

The TAXUS ATLAS Small Vessel and Long

Lesion studies demonstrate successful transfer

of the paclitaxel technology to the next

generation TAXUS Liberté stent.

The new TAXUS Liberté stent design leads to

improved clinical outcomes in small vessels and

long lesions compared to TAXUS Express.

taxus atlas sv and ll 9mtct october 22, 2007, 1pm late breaking trial the taxus liberté 2.25 and...

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