Post on 17-Jan-2016
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 SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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 ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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 ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
TAXUS LibertéTAXUS ATLAS Expansion Program
Non-Inferiority
TAXUSExpress
BMSExpress
Superiority Non-Inferiority
TAXUSExpress
TAXUS LibertéLong (38 mm)
TAXUS ATLASSmall Vessel
TAXUS ATLASLong Lesion
TAXUSLiberté 2.25 mm
Small Vessel
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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)
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
TAXUS LibertéTAXUS ATLAS Expansion Program
Non-Inferiority
TAXUSExpress
BMSExpress
Superiority Non-Inferiority
TAXUSExpress
TAXUSLiberté 2.25 mm
TAXUS LibertéLong (38 mm)
TAXUS ATLASSmall Vessel
TAXUS ATLASLong Lesion
SuperiorityMet
Small Vessel
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
Hyperlipidemia (%) 77.3 82.0 0.37
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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 SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
TAXUS LibertéTAXUS ATLAS Expansion Program
Non-Inferiority
TAXUSExpress
BMSExpress
Superiority Non-Inferiority
TAXUSExpress
TAXUSLiberté 2.25 mm
TAXUS LibertéLong (38 mm)
TAXUS ATLASSmall Vessel
TAXUS ATLASLong Lesion
SuperiorityMet
Non-InferiorityMet
Long Lesion
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
Hyperlipidemia (%) 71.7 85.3 0.0044
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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 SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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 LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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
TAXUS ATLAS SV and LL 9m TCT • October 22, 2007, 1pm • Late Breaking Trial
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.