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Slide 1PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am
TAXUS PERSEUS
A Novel Platinum Chromium, Thin-Strut TAXUS Element Stent for the Treatment of
de novo Coronary Stenoses
Dean J. Kereiakes, MD; Louis A. Cannon, MD
Robert L. Feldman, MD; Gregory J. Mishkel, MD; Abram C. Rabinowitz, MD; Robert Whitbourn, MBBS; Raymond
Magorien, MD; Paul Underwood, MD; Keith D. Dawkins, MD
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 2
Conflict of Interest Disclosures
• Dr. Kereiakes received research grants from Boston
Scientific, Cordis, Medtronic, and Abbott Vascular, and
serves on the Advisory Boards for Boston Scientific and
Abbott Vascular.
The PERSEUS trials and this presentation were sponsored and funded by Boston Scientific Corporation, Natick, MA
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 3
Metal Stainless Steel Stainless Steel Pt Cr
Radial Strength 0.23N/mm 0.24N/mm 0.26N/mm
Density 8.0g/cc 8.0g/cc 9.9g/cc
Strut Thickness 132µm 97µm 81µm
Nickel Content 14% 14% 9%
Challenge Focal Bend Fatigue
1x 12x Relative to Express
306x Relative to Express
Stent Models 2 3 4
Surface-to-Artery Ratio
(acrossdiameters)
11.1-16.7% 11.8-15.8% 12.4-15.1%
Stent Technology Evolution:3 Generations of TAXUS StentPlatinum Chromium (PtCr) Element Stent
TAXUSExpress
TAXUSLiberté
TAXUSElement
Fu
nctio
nD
esi
gn
& D
eliv
ery
Impactof Change
Strength
Enhanced/more uniform
drug distribution
Radiopacity
Fractureresistance
Flexibility
Hypersensitivity
Recoil
Computer simulation Computer simulation Computer simulation
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 4
• PERSEUS Workhorse (WH), ≥2.75mm - ≤4.0mm, ≤28mm
• PERSEUS Small Vessel (SV), ≥2.25mm - <2.75mm, ≤20mm
TAXUS ElementPES (N=942)
TAXUS ElementPES (N=224)
TAXUS ExpressPES (N=320)
Historic BMS Express(TAXUS V) (N=125)
PERSEUS Clinical Trial Program2 parallel Trials in single, de novo lesions
NON-INFERIORITY Design, Randomized 3:1
Primary Endpoint: TLF* (12 mos) • Secondary Endpoint: in-segment %DS (9 mos)**
SUPERIORITY Design, Single Arm, Open Label
Primary Endpoint: in-stent late loss (9 mos) • Secondary Endpoint: TLF (12 mos) vs. Prespecified Performance Goal (PG)
*TLF=ischemia-driven TLR or MI/cardiac death related to target vessel **QCA cohort randomly assigned
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 5
• Bayesian analysis used to power the 1o and 2o endpoints
• Success criteria: ≥95% Bayesian probability that TAXUS Element is non-inferior to TAXUS Express
• Predefined delta: 4.1% (TLF); 0.20 ln(%DS)*
• Standard (frequentist) method used for all other endpoints
Statistical Methods
Allocco et al. Trials 2010;11:1.
PE
RS
EU
S W
HP
ER
SE
US
SV • Frequentist approach used for all endpoints
• 1o Endpoint: 2-sided t-test vs. historical BMS control (TAXUS V)
• 2o Endpoint: 1-sided binomial test vs. a prespecified performance goal*
*Based on TAXUS IV/V results
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 6
Principal Investigators Dean J. Kereiakes, MDLouis A. Cannon, MD
Core Angiographic Laboratory
Jeffrey J. Popma (Director), CardioVascular Institute at Beth Israel Deaconess Medical Center, Boston, MA, USA
Clinical Events Committee Don Cutlip, MD (Chair)Julian Aroesty, MDManish Chauhan, MDGermano DiSciascio, MDKalon K. L. Ho, MD, MScJoseph P. Kannam, MDMichel Vandormael, MD
Data Monitoring Committee W. Douglas Weaver, MD (Chair)David P. Faxon, MDKirk N. Garrett, MD, until August 2008Steven R. Bailey, MD, December 2008 – presentDavid J. Moliterno, MDJan G. P. Tijssen, PhDAdam Greenbaum, MD
PERSEUS Study Organization
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 7
Site Name Principal Investigator #
Munroe Medical Center, Ocala, FL Feldman, Robert L. 91
St. Johns Hospital, Springfield, IL Mishkel, Greg 56
Wake Medical Center, Raleigh, NCMann, Tift
55
TexSan Heart Hospital, San Antonio, TX Rabinowitz, Abram C. 54
The Christ Hospital, Cincinnati, OH Kereiakes, Dean J. 52
St. Vincents Hospital, Melbourne, Australia Whitbourn, Robert 50
Ohio State University Medical Ctr., Columbus, OH Magorien, Raymond 50
Abbott Northwestern Hospital, Minneapolis, MS Mooney, Michael 44
South Denver Cardiology Assoc., Littleton, CO Dauber, Ira M. 42
St. Vincents Hospital, Indianapolis, IN Ball, Michael 39
North Mississippi Medical Center, Tupelo, MS Bertolet, Barry 37
Northern Michigan Hospital, Petoskey, MI Cannon, Louis A. 36
PERSEUS “Top 12” Combined WH & SV
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 8
Clinical & Angiographic CharacteristicsPERSEUS WH RCT
Values are % (n/N) or mean±SD (N)TAXUS Express
(N=320)TAXUS Element
(N=942) P Value
Age, years 63.5±9.5 (320) 62.2±9.6 (942) 0.03
Male 68.8 (220/320) 70.8 (667/942) 0.49
Diabetes 25.0 (80/320) 24.6 (232/942) 0.89
Insulin 7.5 (24/320) 7.3 (69/942) 0.92
Current Smoker 23.5 (73/311) 24.3 (223/916) 0.76
Unstable Angina 21.3 (68/320) 20.7 (195/942) 0.84
Prior CHF 7.5 (24/318) 6.0 (56/937) 0.32
Ejection Fraction 57.8±9.8 (317) 58.0±9.3 (939) 0.73
RVD, mm 2.8±0.5 (320) 2.8±0.5 (942) 0.37
Lesion Length, mm 14.1±5.8 (320) 14.2±6.1 (942) 0.68
Diameter Stenosis 71.7±10.9 (320) 72.1±10.9 (942) 0.58
B2/C Lesions 64.7 (207/320) 66.9 (630/942) 0.47
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 9
Procedural OutcomesPERSEUS WH
Values are % (n/N) or mean±SD (N)TAXUS Express
(N=320)
TAXUS Element
(N=942)
P
Value
Technical Success* 98.8 (338/342 stents) 99.2 (1005/1013 stents) 0.51
Stent Length:Lesion Length 1.60±0.73 (319) 1.55±0.64 (940) 0.25
Multiple Stents† 8.4 (27/320) 7.6 (72/942) 0.65
Max Stent Deploy Pressure 14.0±2.8 (316) 13.7±2.4 (932) 0.15
Post-Dilation Used 53.8 (172/320) 53.6 (505/942) 0.97
Max Post-Dilation Pressure 16.6±3.3 (172) 16.6±3.6 (506) 0.95
†Use of multiple stents for bailout indication only
*Successful stent delivery and deployment to target vessel, without balloon rupture or stent embolization; per stent.
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 10
0.0
1.0
2.0
3.0
4.0
Post-Procedure QCAPERSEUS WH
0.0
1.0
2.0
3.0
4.0MLD (mm) Acute Gain (mm)
2.54±0.36
2.68±0.39
P=0.01 P=0.17
2.16±0.37
2.25±0.49 1.83
±0.40
1.93±0.41
1.45±0.40
1.51±0.48
In-Stent In-Segment In-Stent In-Segment
P=0.09 P=0.41
TAXUS Express PES TAXUS Element PES
(61) (228) (61) (228) (61) (228) (61) (228)
QCA Subset, Paired Lesion Analysis
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 11
-0.1 0 0.1 0.2
Primary/Secondary Endpoints PERSEUS WH (Bayesian Analysis)
1o Clinical Endpoint: TLF(97.7% complete F/U 12 mos)
Posterior Probability ofNon-Inferiority = 0.9996
2o QCA Endpoint: ln(%DS)(87.6% complete F/U 9 mos)
95%CredibleInterval
Posterior Probability ofNon-Inferiority = 0.9970
0.11
P(θ1- θ2 < 4.1% | data) ≥0.95 (μ1 – μ2 < 0.20 | data) ≥0.95
-1 0 1 2 3 4
Δ4.1%
95%CredibleInterval
1.85%
Δ0.20
Difference:-0.57%
Difference:-0.03
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 12
9-M
onth
Lat
e Lo
ss (
mm
)
9-Month QCA OutcomesPERSEUS WH
0.0
0.2
0.4
0.6
0.8
1.0Late Loss (mm)
9-M
onth
% D
iam
eter
Ste
nosi
s
0
20
40
60Diameter Stenosis (%)
0.26±0.52
0.34±0.55
P=0.33 P=0.86
0.16±0.45
0.17±0.48
16.02±20.61
16.37±20.86
26.37±17.47
26.10±17.71
P=0.91 P=0.92
QCA Subset, Paired Lesion Analysis
In-Stent In-Segment In-Stent In-Segment (61) (228) (61) (228) (61) (228) (61) (228)
TAXUS Express PES TAXUS Element PES
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 13
12-Month Clinical OutcomesPERSEUS WH
6.1
7.7
0.3 0.6
2.9
0.3
5.6
7.4
0.5 0.7
2.2
0.4
0
5
10
15
TLF MACE CardiacDeath
All-CauseDeath
MI ST*(ARC Def/Prob)
P=0.78 P=0.86 P>0.99 P>0.99 P=0.48 P>0.99
Eve
nt R
ates
(pe
r P
atie
nt,
%)
*TLF: ischemia-driven TLR, or MI/cardiac death related to the target vessel.†MACE: MI, TVR, cardiac death
TAXUS Express PES (N=320) TAXUS Element PES (N=942)
(1/313) (4/918)(19/313) (52/922) (24/313) (68/922) (1/313) (5/922) (2/314) (6/922) (9/313) (20/922)
*12m DAPT compliance 89%, both groups
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 14
Cum
ulat
ive
Eve
nt R
ate
(%)
Cumulative TLF* to 12 MonthsPERSEUS WH
0
5
10
15
20
0
Days Since Index Procedure
30 60 90 120 150 180 210 240 270 300 330 360 390
TAXUS Element (N=942)
TAXUS Express (N=320)
6.0%5.6%
P=0.78
*TLF: ischemia-driven TLR, or MI/cardiac death related to the target vessel.
23% AngiographicFollow-Up
Event Rate±SE; Log-Rank P ValueTAXUS Element TAXUS Express
Estimated Event Rate
0%
5%
10%
15%
20%
Days Since Index Procedure0 30 60 90 120 150 180 210 240 270 300 330 360 390
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 15
0
1
2
3
4
5
6
TAXUS Element - Non-QCA
Estimated Event Rate
0%
1%
2%
3%
4%
5%
6%
Days Since Index Procedure0 30 60 90 120 150 180 210 240 270 300 330 360 390
TAXUS Express - Non-QCA
Estimated Event Rate
0%
1%
2%
3%
4%
5%
6%
Days Since Index Procedure0 30 60 90 120 150 180 210 240 270 300 330 360 390
Cum
ulat
ive
Eve
nt R
ate
(%)
Comparison of Ischemia-Driven TLRBetween Non-QCA Stent Cohorts
0
Days Since Index Procedure
30 60 90 120 150 180 210 240 270 300 330 360 390
3.4%2.8%
4.5%
2.3%
SPIRIT IV Presented by G. Stone, TCT 2009
PERSEUS, TAXUS Express, Non-QCA subset (N=246)
PERSEUS, TAXUS Element, Non-QCA subset (N=686)
SPIRIT IV, TAXUS Express (N=1229)
Baseline RVDPERSEUS: 2.8mm SPIRIT IV: 2.75mmBaseline Lesion LengthPERSEUS, Element: 14.2mm SPIRIT IV, Xience: 14.8mm
SPIRIT IV, XIENCE V/PROMUS (N=2458)
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 16
Clinical & Angiographic CharacteristicsPERSEUS SV
Values are % (n/N) or mean±SD (N)Historic BMS*
(N=125)TAXUS Element
(N=224)P Value
Age, years 64.2±10.9 (125) 64.7±10.3 (224) 0.64
Male 60.8 (76/125) 63.8 (143/224) 0.57
Diabetes 32.0 (40/125) 36.6 (82/224) 0.39
Current Smoker 22.2 (26/117) 13.6 (30/220) 0.04
Unstable Angina 29.6 (37/125) 20.1 (45/224) 0.04
RVD, mm 2.2±0.4 (125) 2.1±0.3 (224) <0.001
Lesion Length, mm 12.9±5.1 (125) 11.7±5.1 (224) 0.04
Diameter Stenosis 71.5±10.4 (125) 73.5±10.2 (224) 0.08
B2/C Lesions 77.6 (97/125) 58.0 (130/224) <0.001
*TAXUS V
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 17
Post-Procedure QCAPERSEUS SV
0.0
1.0
2.0
3.0
4.0
0.0
1.0
2.0
3.0
4.0MLD (mm) Acute Gain (mm)
2.09±0.30
2.11±0.21
P=0.50 P=0.18
1.76±0.38
1.70±0.29 1.47
±0.33
1.57±0.27
1.14±0.39
1.16±0.30
In-Stent In-Segment In-Stent In-Segment
P=0.007 P=0.55
(108) (197) (108) (197) (108) (197) (108) (197)
Paired Lesion Analysis
Historic BMS Express TAXUS Element PES
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 18
5 10 15
Primary & Secondary EndpointsPERSEUS SV
2o Endpoint: TLF(97.4% complete F/U 12 mos)
7.3% (16/218)
TAXUS ElementMean 12m TLF:
Upper 1-Sided 95% CI
P<0.001
10.8%
PG*19.5%
In
-Ste
nt
Lat
e L
oss
(m
m)
0.0
0.5
1.0
1.5
0.80±0.53 0.38
±0.51
1o Endpoint: Late Loss(87.4% complete F/U 9 mos )
Difference [95% CI]: -0.42 [-0.54,-0.30]
Superiority Met: P<0.001
BMSExpress
TAXUSElement
N=108 N=197
*Prespecified Performance Goal(lesion-matched TAXUS IV/V PES cohort)
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 19
Pro
pens
ity-A
djus
ted
9m I
n-S
tent
Lat
e Lo
ss (
mm
)Propensity Adjustment of Primary Endpoint, PERSEUS SV
0.81
0.37
0.0
0.5
1.0
1.5
In-Stent Late Loss (9m)
Difference [95% CI]: -0.45 [-0.59,-0.31]
Superiority Met: P<0.001
BMSExpress
TAXUSElement
28 Variables Included:
Clinical Angiographic• Age, gender, race• Prior PCI, CABG,
MI, TIA/CVA• PVD• CHF• LVEF• Angina CCS class
3/4• Current smoker• Arrhythmia• Treated diabetes• Hyperlipidemia• Hypertension• Procedural GP
IIb/IIIa
• LAD lesion• RVD• Lesion length• %DS• MLD• Calcification• Bend• Tortuosity• B2/C lesion• Thrombus• Aneurysm
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 20
Clinical Outcomes (12 Month)PERSEUS SV, Propensity Score Adjusted
20.5
30.4
0.4 1.02.5
0.6
6.6
10.5
1.8 1.80.6 0.3
0
10
20
30
40
TLF* MACE† CardiacDeath
All-CauseDeath
MI ST(ARC Def/Prob)
P=0.01 P=0.002 P=0.26 P=0.56 P=0.26 P=0.65
Eve
nt R
ates
(pe
r P
atie
nt,
%)
*TLF: ischemia-driven TLR, or MI/cardiac death related to the target vessel.†MACE: MI, TVR, cardiac death
Historic BMS Express (N=125) TAXUS Element PES (N=224)
PERSEUS Primary Endpoint • Dean Kereiakes • ACC/i2 Late Breaking Trial • Monday, March 15, 2010, 11:06 am Slide 21
ConclusionsPERSEUS WH & SV Studies
• The TAXUS Element stent, which incorporates a novel
platinum chromium metal alloy and thin strut design is:
– Comparable in efficacy to the TAXUS Express stent in
workhorse lesions
– Superior in efficacy to the bare metal Express stent in small
caliber vessels
• No clinical safety concerns regarding the novel platinum
chromium alloy or Element stent design are evident