Slide 1 PERSEUS Primary Endpoint Dean Kereiakes ACC/i2 Late Breaking Trial Monday, March 15, 2010,...

PERSEUS 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


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 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


• 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


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


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


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


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.


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


-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


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


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


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


0

1

2

3

4

5

6

TAXUS Element - Non-QCA


0%

1%

2%

3%

4%

5%

6%


TAXUS Express - Non-QCA


0%

1%

2%

3%

4%

5%

6%


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)


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


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


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)


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


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)


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

Slide 1 PERSEUS Primary Endpoint Dean Kereiakes ACC/i2 Late Breaking Trial Monday, March 15, 2010,...

Documents

Transcript of Slide 1 PERSEUS Primary Endpoint Dean Kereiakes ACC/i2 Late Breaking Trial Monday, March 15, 2010,...