Martin B. Leon, MD for the Endeavor IV investigators Columbia University Medical Center Cardiovascular Research Foundation New York City Monday, September.

Martin B. Leon, MD Martin B. Leon, MD

for the Endeavor IV investigatorsfor the Endeavor IV investigators

Columbia University Medical CenterColumbia University Medical CenterCardiovascular Research FoundationCardiovascular Research Foundation

New York CityNew York City

Monday, September 22, 2009Monday, September 22, 2009

Three-Year Follow-up from a Three-Year Follow-up from a Prospective Randomized Trial Prospective Randomized Trial

Comparing a Zotarolimus-Eluting Stent Comparing a Zotarolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients and a Paclitaxel-Eluting Stent in Patients

with Coronary Artery Diseasewith Coronary Artery Disease

ENDEAVOR IVENDEAVOR IV

Primary Endpoint: TVF at 9 monthsPrimary Endpoint: TVF at 9 monthsSecondary Endpoints: In-segment % DS at 8 months; TLR and TVR at 9 monthsSecondary Endpoints: In-segment % DS at 8 months; TLR and TVR at 9 months

Drug Therapy: ASA and Clopidogrel/Ticlid Drug Therapy: ASA and Clopidogrel/Ticlid ≥≥6 months6 monthsZotarolimus Dose: 10 Zotarolimus Dose: 10 g per mm stent lengthg per mm stent length

Primary Endpoint: TVF at 9 monthsPrimary Endpoint: TVF at 9 monthsSecondary Endpoints: In-segment % DS at 8 months; TLR and TVR at 9 monthsSecondary Endpoints: In-segment % DS at 8 months; TLR and TVR at 9 months

Drug Therapy: ASA and Clopidogrel/Ticlid Drug Therapy: ASA and Clopidogrel/Ticlid ≥≥6 months6 monthsZotarolimus Dose: 10 Zotarolimus Dose: 10 g per mm stent lengthg per mm stent length

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FU

Single Single De NovoDe Novo Native Coronary Lesion Native Coronary LesionVessel Diameter: 2.5–3.5 mmVessel Diameter: 2.5–3.5 mm

Lesion Length: ≤ 27 mmLesion Length: ≤ 27 mmPre-dilatation requiredPre-dilatation required

30d30d 6mo6mo 4yr4yr3yr3yr2yr2yr9mo9mo 12mo12mo8mo8mo 5yr5yrClinical/MACEClinical/MACE

Angiography/IVUSAngiography/IVUS

QCA and IVUS QCA and IVUS SubsetSubset

(328 total = 21.2%)(328 total = 21.2%)

Clinical Trial Design Clinical Trial Design PIs: Martin B. Leon and David E KandzariPIs: Martin B. Leon and David E Kandzari

1:1 randomizationN = 1,548 patients

80 sitesUS

Endeavor Stent n = 774

Taxus Stentn = 774

Endeavor IV - Endeavor IV - Top EnrollersTop Enrollers PatientsPatients PatientsPatients

C. O’ShaughnessyC. O’ShaughnessyElyria Memorial Hospital, Elyria, OHElyria Memorial Hospital, Elyria, OH 119119 J. PattersonJ. Patterson

Forsyth Medical Center, Winston-Salem, NCForsyth Medical Center, Winston-Salem, NC 2929

P. OverlieP. OverlieLubbock heart Hospital, Lubbock, TXLubbock heart Hospital, Lubbock, TX

9595M. SketchM. SketchDuke University Medical Center, Durham, Duke University Medical Center, Durham, NCNC

2828

B. McLaurinB. McLaurinAnderson Medical Center, Anderson, SCAnderson Medical Center, Anderson, SC 6363 M. LeonM. Leon

Columbia Presbyterian Center NY, NY, NYColumbia Presbyterian Center NY, NY, NY 2828

S. SolomonS. SolomonMethodist Hospital Houston, Houston, TXMethodist Hospital Houston, Houston, TX 5959 P. ColemanP. Coleman

Sutter Medical Center, Santa Rosa, CASutter Medical Center, Santa Rosa, CA 2727

J. DouglasJ. DouglasEmory Clinic, Atlanta, GAEmory Clinic, Atlanta, GA 5151 R. StolerR. Stoler

Baylor Heart & Vascular, Dallas, TXBaylor Heart & Vascular, Dallas, TX 2626

M. BallM. BallHeart Center of Indiana, Indianapolis, INHeart Center of Indiana, Indianapolis, IN 5151 S. PapadakosS. Papadakos

New York Hospital of Queens, Flushing, NYNew York Hospital of Queens, Flushing, NY 2626

R. CaputoR. CaputoSt. Joseph Hospital health Center, St. Joseph Hospital health Center, Syracuse, NYSyracuse, NY

5050 J. SinghJ. SinghBarnes Jewish, St. Louis, MOBarnes Jewish, St. Louis, MO

2323

A. JainA. JainWashington Hospital Healthcare, Washington Hospital Healthcare, Fremont, CAFremont, CA

4747 D. PintoD. PintoBeth Israel Hospital, Boston, MABeth Israel Hospital, Boston, MA

2323

T. TollesonT. TollesonMother Francis health System, Tyler, TXMother Francis health System, Tyler, TX 4545 B. RutherfordB. Rutherford

St. Luke’s Hospital, Kansas City, MOSt. Luke’s Hospital, Kansas City, MO 2323

B. ReenB. ReenPrsbyterian hospital, Charlotte, NCPrsbyterian hospital, Charlotte, NC 4444 V. ChilakamarriV. Chilakamarri

Lutheran Hospital of IN, Fort Wayne, INLutheran Hospital of IN, Fort Wayne, IN 2222

H. LibermanH. LibermanEmory Crawford Long, Atlanta, GAEmory Crawford Long, Atlanta, GA 3636 R. PrashadR. Prashad

Ocala Regional Medical Center, Ocala, FLOcala Regional Medical Center, Ocala, FL 2222

H. WilsonH. WilsonCarolinas Medical Center, Charlotte, NCCarolinas Medical Center, Charlotte, NC 3030 T. BassT. Bass

University of Florida, Jacksonville, FLUniversity of Florida, Jacksonville, FL 2222

P. BajwaP. BajwaNebraska Heart Institute, Lincoln, NENebraska Heart Institute, Lincoln, NE

2929T. SacchiT. SacchiNY Methodist/Cornell Heart Center, NY Methodist/Cornell Heart Center, Brooklyn, NYBrooklyn, NY

2020

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUPatient DemographicsPatient Demographics

EndeavorEndeavor(773 pts)(773 pts)

TaxusTaxus(775 pts)(775 pts) P P valuevalue

Age (in years)Age (in years) 63.5 ± 11.163.5 ± 11.1 63.6 ± 11.063.6 ± 11.0 0.9300.930

Men (%)Men (%) 66.966.9 68.568.5 0.5140.514

Diabetes (%)Diabetes (%) 31.231.2 30.530.5 0.7830.783

IDDM (%)IDDM (%) 10.310.3 8.38.3 0.1620.162

Prior MI (%)Prior MI (%) 21.121.1 23.223.2 0.3240.324

Angina – Stable (%)Angina – Stable (%) Unstable (%) Unstable (%) MI (%) MI (%)

45.645.651.651.62.82.8

47.947.949.949.92.12.1

0.3670.367

EndeavorEndeavor(773 lesions)(773 lesions)

TaxusTaxus(775 lesions)(775 lesions) P P valuevalue

CAD – Single Vessel (%)CAD – Single Vessel (%) 54.954.9 57.257.2 0.3840.384

Vessel Location (%)Vessel Location (%) 0.7910.791

LADLAD 42.242.2 41.541.5

ACC/AHA Lesion ClassACC/AHA Lesion Class 0.3580.358

BB22/C/C 69.669.6 70.970.9

QCAQCA

RVD (mm)RVD (mm) 2.73 ± 0.472.73 ± 0.47 2.70 ± 0.462.70 ± 0.46 0.1970.197

MLD (mm)MLD (mm) 0.96 ± 0.400.96 ± 0.40 0.93 ± 0.400.93 ± 0.40 0.1490.149

% DS% DS 64.83 ± 13.2964.83 ± 13.29 65.68 ± 13.1065.68 ± 13.10 0.2040.204

Lesion Length (mm)Lesion Length (mm) 13.41 ± 5.6713.41 ± 5.67 13.80 ± 6.0913.80 ± 6.09 0.1990.199

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FULesion Characteristics (QCA)Lesion Characteristics (QCA)

Patients EnrolledPatients EnrolledN = 1548N = 1548

RandomizedRandomizedEndeavorn = 773

Clinical F/U(12 mo)756/77397.8%

Taxusn = 775

Clinical F/U(12 mo)757/77597.7%

Clinical F/U(36 mo) 734/77395.0%

Clinical F/U(36 mo)734/775 94.7%

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUPatient Flow ChartPatient Flow Chart

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUTVF to 36 monthsTVF to 36 months

EndeavorEndeavor 773773 769769 749749 736736 700700 680680 662662 655655 645645 633633 620620 615615 610610

TaxusTaxus 775775 755755 739739 719719 694694 668668 656656 647647 639639 621621 607607 596596 589589

20%

15%

10%

5%

0%Cu

mu

lati

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cid

ence

fo

r T

VF

0 90 180 270 360 450 540 630 720 810 900 990 1080

Time after Initial Procedure (days)

Values are the KM estimatesValues are the KM estimatesPP values were calculated by Log Rank Test values were calculated by Log Rank Test

1-year HR0.79 [0.56, 1.11]

P=0.166

9.6%

7.7%

∆∆1.9%1.9%

3-year HR0.77 [0.58, 0.99]

P = 0.049 15.9%

12.3%

∆∆3.6%3.6%

EndeavorTaxus

12.4%

9.9%

16.1%

7.1%

10.9%

3.7%

Cardiac Death/MICardiac Death/MI

Rat

eR

ate

==

Endeavor (n=734)

Taxus (n=734)

TVFTVF TVRTVR

P =0.608P =0.608P =0.608P =0.608

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUPrimary EP TVF to 36 months Primary EP TVF to 36 months

RRR 23%RRR 23%NNT: 27NNT: 27P=0.052P=0.052

RRR 23%RRR 23%NNT: 27NNT: 27P=0.052P=0.052

RRR 48%RRR 48%NNT: 29NNT: 29P=0.005P=0.005

RRR 48%RRR 48%NNT: 29NNT: 29P=0.005P=0.005

++

91/734 118/734 73/73427/734 52/734 80/734

Values are the event ratesValues are the event ratesP values were calculated by Fisher Exact TestP values were calculated by Fisher Exact Test

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUCD/MI to 36 monthsCD/MI to 36 months

10%

8%

6%

4%

0%

Cu

mu

lati

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cid

ence

of

Car

dia

c D

eath

/MI

0 90 180 270 360 450 540 630 720 810 900 990 1080


2%


TaxusTaxus 775775 758758 747747 738738 727727 715715 702702 698698 693693 678678 667667 658658 650650


1-year HR0.66 [0.35, 1.25]

P=0.201∆∆1.0%1.0%

3.1%

2.1%3.6%

7.1%

∆∆3.5%3.5%

3-year HR0.52 [0.32, 0.82]

P = 0.004

EndeavorTaxus

CD

/MI (

%)


ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUCD/MI Landmark to 36 monthsCD/MI Landmark to 36 months

EndeavorTaxus


0.0%

2.0%

4.0%

6.0%

0 90 180 270 360 450 540 630 720 810 900 990 1080

1.7%

4.0%

∆∆2.3%2.3%

P = 0.012

1-3 year HR0.43 [0.22, 0.84]

3.1%

2.1%

∆∆1.0%1.0%

1-year HR0.66 [0.35, 1.25]

P=0.201

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUMI Landmark toMI Landmark to 36 36 monthsmonths

MI (

%)


EndeavorTaxus


0.0%

1.0%

2.0%

3.0%

0 90 180 270 360 450 540 630 720 810 900 990 1080

0.7%

2.3%

∆∆1.6%1.6%

P = 0.017

1-3 year HR0.31 [0.12, 0.86]

1 year HR0.60 [0.29, 1.23]

2.6%

1.6%

∆∆1.0%1.0%

P=0.154P=0.154

0 0

2

4

0

10

≥≥5X<8X5X<8X ≥≥8X<10X8X<10X ≥≥10X10X

Nu

mb

er

Pa

tie

nts

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUAll MIs CKMB Rises (xULN) All MIs CKMB Rises (xULN) 1-3 years1-3 years

10/16 (63%) of Taxus MIs 10/16 (63%) of Taxus MIs with CKMB rises with CKMB rises 10X ULN 10X ULN

2/4 Endeavor MIs and 2/16 Taxus MIs CKMB (xULN) <5X2/4 Endeavor MIs and 2/16 Taxus MIs CKMB (xULN) <5X

Endeavor

Taxus

Length of DAPTLength of DAPT EndeavorEndeavor TaxusTaxus P P valuevalue

180 days on (%)180 days on (%) 92.192.1 91.491.4 0.6390.639

270 days on (%)270 days on (%) 54.554.5 54.554.5 1.0001.000

360 days on (%)360 days on (%) 57.657.6 57.257.2 0.8730.873

720 days on (%)720 days on (%) 65.465.4 71.371.3 0.0190.019

1080 days on (%)1080 days on (%) 48.248.2 52.152.1 0.1740.174

* Physicians and patients unblinded at 12 months* Physicians and patients unblinded at 12 months

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUDAPT to 36 months* DAPT to 36 months*

0.1% 0.1%

0.8%0.7%

1.5%

0.0%

Rat

eR

ate

Endeavor (n=734)

Taxus (n=734)

ARC DefiniteARC Definite ARC ProbableARC Probable ARC DefiniteARC DefiniteProbableProbable

n=6 n=11n=1n=5n=1

P =0.124P =0.124P =0.124P =0.124P =0.062P =0.062P =0.062P =0.062

P =0.006P =0.006P =0.006P =0.006

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUARC VLST 12-36 mos ARC VLST 12-36 mos

RRR 91%RRR 91%NNT: 71NNT: 71P=0.006P=0.006

RRR 91%RRR 91%NNT: 71NNT: 71P=0.006P=0.006

Values are the event ratesValues are the event ratesP values were calculated by Fisher Exact TestP values were calculated by Fisher Exact Test

4%

2%

0%


Cu

mu

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cid

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o

f D

ef/P

rob

Th

rom

bo

sis

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FU ARC ST Def/Prob 12-36 ARC ST Def/Prob 12-36 mosmos (VLST) (VLST)

EndeavorEndeavor 732732 732732 719719 716716 710710 699699 688688 684684 680680

TaxusTaxus 734734 734734 721721 718718 714714 701701 690690 681681 674674

360 450 540 630 720 810 900 990 1080

0.1%

1.6%

∆∆1.5%1.5%

1-3 year HR0.09 [0.01, 0.71]

P = 0.004

EndeavorTaxus


Days360 480 600 720 840 960 1080

Endeavor

Taxus

413495

619645

689697

835838

878949

1024

Taxus VLST ( n=11)Taxus VLST ( n=11)5/11 On ASA and Plavix 5/11 On ASA and Plavix 4/11 on ASA4/11 on ASA2/11 No DAPT2/11 No DAPT2/11 Resulted in a TLR2/11 Resulted in a TLR9/11 Resulted in an AMI9/11 Resulted in an AMI

369 Endeavor VLST ( n=1)Endeavor VLST ( n=1)1/1 No DAPT1/1 No DAPT1/1 Resulted in an AMI1/1 Resulted in an AMI

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUTiming of ARC Def/Prob VLSTTiming of ARC Def/Prob VLST

5 Taxus VLST events from 2-3 years

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUTLR to 36 monthsTLR to 36 months

10%

8%

6%

4%

0%Cu

mu

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cid

ence

fo

r T

LR

0 90 180 270 360 450 540 630 720 810 900 990 1080


2%


TaxusTaxus 775775 771771 758758 742742 712712 695695 682682 677677 674674 659659 646646 635635 628628


1-year HR1.36 [0.81, 2.28]

P=0.239

4.5%

3.3%

∆∆1.2%1.2%

6.5%

6.1%

∆∆0.4%0.4%

3-year HR1.10 [0.73, 1.65]

P = 0.662

EndeavorTaxus

TL

R

Ra

te

1 2 3

Years of Follow-up

1 2 3

Years of Follow-up

Endeavor(Yr 3 N = 734/773)

Taxus(Yr 3 N = 734/775)

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUTLR Rate Over TimeTLR Rate Over Time

82%82% Increase Increase44%44% Increase Increase

Values are the event ratesValues are the event rates

4.5%

3.3%

5.9%

6.5%6.0%

4.5%

5 Year Clinical Results of TAXUS IV, Stone, ACC 2007Results come from separate clinical trials. Data may differ in a head-to-head comparison.

ENDEAVOR II(n=577/598)

TL

R (

%)

1 2 3 4 5

6.57.2 7.2

7.5

Years of Follow-up

Endeavor II and Taxus IV: DES Arms Endeavor II and Taxus IV: DES Arms TLR Rates to 5 years TLR Rates to 5 years

TAXUS IV(n=618/662)

TL

R (

%)

1 2 3 4 5

5.9

4.4

5.6

6.9

7.8

9.1

Years of Follow-up

27%27% Increase Increase

106%106% Increase Increase

Subgroup Post-Hoc AnalysisSubgroup Post-Hoc AnalysisENDEAVOR IVENDEAVOR IV

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUTVF (36 mos) – Post Hoc Analysis TVF (36 mos) – Post Hoc Analysis

0.800.80 15.6% (35)15.6% (35) 21.6% (47)21.6% (47) 0.6590.659

0.72 11.0% (56)11.0% (56) 13.8% (71)13.8% (71)

Risk Ratio [95% CI]

Risk Ratio Endeavor TaxusP-Value

Interaction

Diabetes

Non-diabetes

RVD

2.5mm

>2.5 <3.0mm

3.0mm

Lesion Length

10mm10mm

>10 <20mm>10 <20mm

20mm20mm

FavorsEndeavor

FavorsTaxus

11 10100.10.1

0.600.60 11.8% (29)11.8% (29) 19.8% (51)19.8% (51) 0.2780.278

0.96 13.8% (40)13.8% (40) 14.4% (41)14.4% (41)

0.82 11.2% (22)11.2% (22) 13.7% (26)13.7% (26)

0.550.55 10.1% (23)10.1% (23) 18.6% (41)18.6% (41) 0.7990.799

0.95 13.6% (57)13.6% (57) 14.4% (58)14.4% (58)

0.66 11.5% (10)11.5% (10) 17.4% (19)17.4% (19)

0.820.82 12.0% (82)12.0% (82) 14.7% (95)14.7% (95) 0.7430.743

0.73 18.6% (8)18.6% (8) 25.3% (71)25.3% (71)

TVF (Target Vessel Failure) is defined as cardiac death, MI or TVR TVF (Target Vessel Failure) is defined as cardiac death, MI or TVR

Single Stent

Multiple Stents

OVERALL 0.77 12.4% (99)12.4% (99) 16.1% (118)16.1% (118) PPdiffdiff=0.052=0.052

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FU CD/MI (36 mos) – Post Hoc Analysis CD/MI (36 mos) – Post Hoc Analysis

0.360.36 2.7% (6)2.7% (6) 7.3% (16)7.3% (16) 0.3760.376

0.59 4.1% (21)4.1% (21) 7.0% (36)7.0% (36)

Risk Ratio [95% CI]


Interaction

Diabetes

Non-diabetes

RVD

2.5mm

>2.5 <3.0mm

3.0mm

Lesion Length

10mm10mm

>10 <20mm>10 <20mm

20mm20mm

Single Stent

Multiple Stents

OVERALLFavors

EndeavorFavorsTaxus

11 10100.10.1

0.260.26 2.0% (5)2.0% (5) 7.8% (20)7.8% (20) 0.1430.143

0.76 4.8% (14)4.8% (14) 6.3% (18)6.3% (18)

0.55 4.1% (8)4.1% (8) 7.4% (14)7.4% (14)

0.220.22 1.8% (4)1.8% (4) 8.1% (18)8.1% (18) 0.8870.887

0.81 5.0% (21)5.0% (21) 6.2% (25)6.2% (25)

0.28 2.3% (2)2.3% (2) 8.3% (9)8.3% (9)

0.560.56 3.7% (25)3.7% (25) 6.5% (42)6.5% (42) 0.6150.615

0.39 4.7% (2)4.7% (2) 12.0% (9)12.0% (9)

0.52 3.7% (27)3.7% (27) 7.1% (52)7.1% (52) PPdiffdiff=0.005=0.005

ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUTVR (36 mos) – Post Hoc Analysis TVR (36 mos) – Post Hoc Analysis

0.920.92 14.3% (32)14.3% (32) 15.6% (34)15.6% (34) 0.9780.978

0.90 8.0% (41)8.0% (41) 8.9% (46)8.9% (46)

Risk Ratio [95% CI]


Interaction

Diabetes

Non-diabetes

RVD

2.5mm

>2.5 <3.0mm

3.0mm

Lesion Length

10mm10mm

>10 <20mm>10 <20mm

20mm20mm

FavorsEndeavor

FavorsTaxus

11 10100.10.1

0.740.74 10.6% (26)10.6% (26) 14.3% (37)14.3% (37) 0.1910.191

0.98 10.0% (29)10.0% (29) 10.2% (29)10.2% (29)

1.24 9.1% (18)9.1% (18) 7.4% (14)7.4% (14)

0.660.66 9.3% (21)9.3% (21) 14.0% (31)14.0% (31) 0.9230.923

1.06 10.3% (43)10.3% (43) 9.7% (39)9.7% (39)

1.00 9.2% (8)9.2% (8) 9.2% (10)9.2% (10)

1.011.01 9.7% (66)9.7% (66) 9.6% (62)9.6% (62) 0.5240.524

0.75 14.0% (6)14.0% (6) 18.7% (14)18.7% (14)

Single Stent

Multiple Stents

OVERALL 0.98 9.9% (73)9.9% (73) 10.9% (80)10.9% (80) PPdiffdiff=0.608=0.608

DiabeticsDiabeticsEndeavor IVEndeavor IV

9.8%

15.6%

12.9%

8.7%

15.6%

21.6%

16.5%

14.3%

TVFTVF

Rat

eR

ate

TVRTVR

Endeavor (n=224)

Taxus (n=218)

TLRTLR MACEMACE

P =0.744P =0.744P =0.744P =0.744

P =0.347P =0.347P =0.347P =0.347

P =0.790P =0.790P =0.790P =0.790

ENDEAVOR IV – 3yr FU ENDEAVOR IV – 3yr FU DiabeticsDiabeticsEfficacy Endpoints to 36 months Efficacy Endpoints to 36 months

P values were calculated by Fisher Exact TestP values were calculated by Fisher Exact TestValues are the event ratesValues are the event rates

P =0.113P =0.113P =0.113P =0.113

22/224 19/218 35/22432/224 34/218 47/218 29/224 36/218

1.3%

0.0%

1.3%

2.7%

4.1%3.7%

0.5%

3.2%

7.3%

1.3%

Non-QNon-Q

Rat

eR

ate

P =0.084P =0.084

MI AllMI All Q-waveQ-wave

Endeavor (n=224)

Taxus (n=218)

Cardiac Cardiac Death Death

Cardiac DeathCardiac Deathand MIand MI

P values were calculated by Fisher Exact TestP values were calculated by Fisher Exact TestValues are the event ratesValues are the event rates

ENDEAVOR IV – 3yr FU DiabeticsENDEAVOR IV – 3yr FU DiabeticsSafety Endpoints to 36 months Safety Endpoints to 36 months

P =0.136P =0.136

P =0.493P =0.493

P =0.216P =0.216

3/224 9/218 13/224 9/218 1/218 3/224 7/218 6/224 16/218

P =0.029P =0.029

ENDEAVOR IV – 3yr FU ENDEAVOR IV – 3yr FU DiabeticsDiabetics

CD/MI to 36 monthsCD/MI to 36 months

EndeavorEndeavor 241241 241241 236236 233233 230230 227227 220220 220220 220220 215215 209209 206206

TaxusTaxus 236236 234234 231231 228228 223223 220220 216216 214214 213213 207207 202202 198198

14%

10%

4%

2%

0%0 90 180 270 360 450 540 630 720 810 900 990 1080


Endeavor Taxus

6%

8%

12%

Cu

mu

lati

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cid

ence

o

f C

ard

iac

Dea

th o

r M

I

Program ConsistencyProgram ConsistencyEndeavor IVEndeavor IV

Endeavor Randomized Clinical Endeavor Randomized Clinical TrialsTrialsCD/MI at Latest Available Follow-upCD/MI at Latest Available Follow-up

6.6%

8.4%

0%

5%

10%

15%

Driver Endeavor

Endeavor IIto 5 years

HR [95%CI]1.28 [0.85-1.92]

P=0.265

1.3%

5.5%

0%

5%

10%

15%

Cypher Endeavor

Endeavor IIIto 4 years

HR [95%CI]4.19 [1.20-14.6]

P=0.024NNH=24

3.7%

7.1%

0%

5%

10%

15%

Taxus Endeavor

Endeavor IVto 3 years

HR [95%CI]1.93 [1.22-3.03]

P=0.005NNH=29

49/582 38/577 6/110 4/307 52/734 27/734

Endeavor Randomized Clinical Endeavor Randomized Clinical TrialsTrialsTLR at Latest Available Follow-upTLR at Latest Available Follow-up

7.5%

16.3%

0%

5%

10%

15%

20%

Driver Endeavor

Endeavor IIto 5 years

HR [95%CI]2.19 [2.56-3.08]

P<0.001NNT=11

7.8%6.4%

0%

5%

10%

15%

20%

Cypher Endeavor

Endeavor IIIto 4 years

HR [95%CI]0.81 [0.36-1.84]

P=0.832

6.5%6.0%

0%

5%

10%

15%

20%

Taxus Endeavor

Endeavor IVto 3 years

HR [95%CI]0.92 [0.62-1.36]

P=0.747

95/582 43/577 7/110 24/307 44/734 48/734

1yr 2yr 3yr 4yr 5yr1yr 2yr 3yr 4yr 5yr

Continued Access Single Arm (n = 296) 4yrContinued Access Single Arm (n = 296) 4yrContinued Access Single Arm (n = 296) 4yrContinued Access Single Arm (n = 296) 4yrENDEAVOR II CAENDEAVOR II CA

ENDEAVOR IENDEAVOR I Single Arm First-in-Man (n = 100) 5yrSingle Arm First-in-Man (n = 100) 5yrSingle Arm First-in-Man (n = 100) 5yrSingle Arm First-in-Man (n = 100) 5yr

ENDEAVOR IIENDEAVOR II

ENDEAVOR IIIENDEAVOR III

ENDEAVOR IVENDEAVOR IV 1:1 RCT vs. Taxus1:1 RCT vs. Taxus®® (E = 773,T = 775) 3yr (E = 773,T = 775) 3yr1:1 RCT vs. Taxus1:1 RCT vs. Taxus®® (E = 773,T = 775) 3yr (E = 773,T = 775) 3yr

ENDEAVOR PKENDEAVOR PK

Single Arm (n = 99) 2yrSingle Arm (n = 99) 2yrSingle Arm (n = 99) 2yrSingle Arm (n = 99) 2yrENDEAVOR JapanENDEAVOR Japan

Premarket Safety and Efficacy Package

Endeavor Clinical Program Endeavor Clinical Program Pooled Safety and Efficacy AnalysesPooled Safety and Efficacy Analyses

1:1 RCT vs. BMS (E = 598,D = 599) PK (n = 106) 5yr1:1 RCT vs. BMS (E = 598,D = 599) PK (n = 106) 5yr1:1 RCT vs. BMS (E = 598,D = 599) PK (n = 106) 5yr1:1 RCT vs. BMS (E = 598,D = 599) PK (n = 106) 5yr

3:1 RCT vs. Cypher® (E = 323,C = 113) 3:1 RCT vs. Cypher® (E = 323,C = 113) 4yr4yr3:1 RCT vs. Cypher® (E = 323,C = 113) 3:1 RCT vs. Cypher® (E = 323,C = 113) 4yr4yr

Pharmacokinetic Study (n = 43) 3yrPharmacokinetic Study (n = 43) 3yrPharmacokinetic Study (n = 43) 3yrPharmacokinetic Study (n = 43) 3yr

Included in Pooled Safety and Efficacy Analyses Included in Pooled Safety and Efficacy Analyses (N=2132)(N=2132)

Included in Pooled Safety and Efficacy Analyses Included in Pooled Safety and Efficacy Analyses (N=2132)(N=2132)

0%

20%

40%

60%

80%

100%

120%

0 360 720 1080 1440 1800

Ad

her

ence

to

DA

PT

(%

)

Days

DAPTDAPT11: E I, E II, E II CA, E III was ≥3 months : E I, E II, E II CA, E III was ≥3 months

Endeavor: E I, E II, EII CA, E III, E IV (n = 2132)

DAPTDAPT11: E IV was ≥6 months : E IV was ≥6 months

8%8%

24%31%

39%

76%

96%

1. Protocol requirementDAPT usage based on case report forms.The optimal duration of dual antiplatelet therapy, specifically clopidogrel, is unknown and DES thrombosis may still occur despite continued therapy.

Endeavor Clinical Program Endeavor Clinical Program Pooled DAPT Compliance to 5 yrsPooled DAPT Compliance to 5 yrs

Cu

mu

lati

ve In

cid

ence

of

TL

R

360 720 1080 14400%

0

20%

25%

EndeavorEndeavor 21322132 21302130 19071907 18401840 15471547 10301030

% CI% CI 0.09%0.09% 5.43%5.43% 6.23%6.23% 6.75%6.75% 6.84%6.84% 6.95%6.95%

DriverDriver 596596 595595 489489 474474 456456 445445

% CI% CI 0.17%0.17% 13.16%13.16% 14.23%14.23% 14.78%14.78% 15.91%15.91% 16.49%16.49%

Values are the KM estimates.Values are the KM estimates.PP-values were calculated by Log Rank Test.-values were calculated by Log Rank Test.

15%

10%

5%

1800Time After Initial Procedure (days)

Endeavor Driver

Endeavor Pooled Efficacy Analysis Endeavor Pooled Efficacy Analysis Cumulative Incidence of TLR to 5 yearsCumulative Incidence of TLR to 5 years

7.0%

16.5%Before 1 yearBefore 1 yearEndeavor: 5.4%Endeavor: 5.4%Driver: 13.2%Driver: 13.2%

Before 1 yearBefore 1 yearEndeavor: 5.4%Endeavor: 5.4%Driver: 13.2%Driver: 13.2%

After 1 year After 1 year Endeavor: 1.6%Endeavor: 1.6%Driver: 3.3%Driver: 3.3%


Cu

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Car

dia

c D

eath

or

MI

360 720 1080 14400%

0

15%


% CI% CI 1.41%1.41% 2.83%2.83% 3.42%3.42% 3.77%3.77% 4.42%4.42% 5.42%5.42%

DriverDriver 596596 581581 555555 544544 529529 523523

% CI% CI 2.52%2.52% 4.54%4.54% 5.75%5.75% 6.62%6.62% 6.98%6.98% 8.42%8.42%


10%

5%

1800Time After Initial Procedure (days)

Endeavor Driver

5.4%

8.4%

ENDEAVOR Pooled Safety Analysis ENDEAVOR Pooled Safety Analysis Cumulative Incidence of CD/MI to 5 yearsCumulative Incidence of CD/MI to 5 years





Endeavor Pooled Safety Analysis Endeavor Pooled Safety Analysis ARC Definite/Probable ST to 5 yearsARC Definite/Probable ST to 5 years

Time After Initial Procedure (days)

Cu

mu

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ve In

cid

ence

of

Def

/Pro

b T

hro

mb

osi

s

360 720 1080 14400%

0

4%


% CI% CI 0.05%0.05% 0.62%0.62% 0.71%0.71% 0.71%0.71% 0.80%0.80% 0.80%0.80%

DriverDriver 596596 595595 570570 559559 543543 538538

% CI% CI 0.17%0.17% 1.35%1.35% 1.35%1.35% 1.52%1.52% 1.52%1.52% 1.71%1.71%


3%

2%

1800

1%

Endeavor Driver

0.8%

1.7%



After 1 year (VLST)After 1 year (VLST)Endeavor: 0.2%Endeavor: 0.2%Driver: 0.4%Driver: 0.4%

After 1 year (VLST)After 1 year (VLST)Endeavor: 0.2%Endeavor: 0.2%Driver: 0.4%Driver: 0.4%

Conclusions: Endeavor IV Conclusions: Endeavor IV Late clinical FU (from 1-3 years) from theLate clinical FU (from 1-3 years) from the

Endeavor IV RCT demonstratesEndeavor IV RCT demonstrates::

• Endeavor has a significant safety advantage cw Endeavor has a significant safety advantage cw TaxusTaxus; overall, 48% reduction in cardiac death + ; overall, 48% reduction in cardiac death + MI (P=0.004) due to a 91% reduction in VLST from MI (P=0.004) due to a 91% reduction in VLST from 1-3 yrs (11 vs. 1 events; P=0.004). The VLST 1-3 yrs (11 vs. 1 events; P=0.004). The VLST frequency of Endeavor (0.1%) is similar to a bare frequency of Endeavor (0.1%) is similar to a bare metal stent.metal stent.

• Endeavor @ 3 years, reduced TVF, the 1Endeavor @ 3 years, reduced TVF, the 1ryry study study endpoint, by 23%, from 15.9% to 12.3% (P=0.049)endpoint, by 23%, from 15.9% to 12.3% (P=0.049)

• Overall TLR @ 3 years was similar (Endeavor Overall TLR @ 3 years was similar (Endeavor 6.5% vs. Taxus 6.0%) with a trend suggesting less 6.5% vs. Taxus 6.0%) with a trend suggesting less late TLR (after 1 year) associated with Endeavor.late TLR (after 1 year) associated with Endeavor.

Conclusions: Endeavor ProgramConclusions: Endeavor ProgramIn In More than 2100 patients studied with over More than 2100 patients studied with over

1000 patients now out to 5 years in pooled 1000 patients now out to 5 years in pooled analysis:analysis:

•Low 7% TLR at 5 years in more than 1000 patients Low 7% TLR at 5 years in more than 1000 patients in ENDEAVOR Pooled Analysisin ENDEAVOR Pooled Analysis

•Despite only 39% of patients on DAPT at 1 year in Despite only 39% of patients on DAPT at 1 year in ENDEAVOR ENDEAVOR PooledPooled Analysis Analysis::11

– LowLow 0.8% ST 0.8% ST22 to 5 years (BMS = 1.7%, to 5 years (BMS = 1.7%, pp = = 0.061)0.061)

– Extremely low 0.2% VLSTExtremely low 0.2% VLST22 after 1 year through after 1 year through 5 years5 years

– Significant reduction in CD/MI Significant reduction in CD/MI vs. vs. BMS at 5 BMS at 5 years (Endeavor 5.5% years (Endeavor 5.5% vs.vs. BMS 8.4%, BMS 8.4%, pp = 0.009) = 0.009)

Martin B. Leon, MD for the Endeavor IV investigators Columbia University Medical Center Cardiovascular Research Foundation New York City Monday, September.

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