endeavor iv · endeavor iv – 3yr fu. single . de novode novo . native coronary lesion vessel...

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C201002706EE

5/09

ThreeThree--Year FollowYear Follow--up from a up from a Prospective Randomized Trial Prospective Randomized Trial Comparing a ZotarolimusComparing a Zotarolimus--Eluting Stent Eluting Stent and a Paclitaxeland a Paclitaxel--Eluting Stent in Patients Eluting Stent in Patients with Coronary Artery Diseasewith Coronary Artery Disease

ENDEAVOR IVENDEAVOR IV


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

Drug Therapy: ASA and Clopidogrel/Ticlid

≥6 monthsZotarolimus Dose: 10 μg per mm stent length

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

Drug Therapy: ASA and Drug Therapy: ASA and Clopidogrel/TiclidClopidogrel/Ticlid

≥≥6 months6 monthsZotarolimus Dose: 10 Zotarolimus Dose: 10 μμg per mm stent lengthg per mm stent length

ENDEAVOR IV ENDEAVOR IV ––

3yr FU3yr FU

Single Single De NovoDe Novo Native Coronary LesionNative Coronary LesionVessel Diameter: 2.5Vessel Diameter: 2.5––3.5 mm3.5 mm

Lesion Length: Lesion Length: ≤≤

27 mm27 mmPrePre--dilatation requireddilatation required

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

Angiography/IVUSAngiography/IVUSQCA and IVUS QCA and IVUS

SubsetSubset

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

Clinical Trial DesignClinical 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®

DES n = 774

Taxus ®DESn = 774


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PatientsPatients PatientsPatients

C. OC. O’’ShaughnessyShaughnessy

Elyria Memorial Hospital, Elyria, OHElyria Memorial Hospital, Elyria, OH 119119 J. PattersonJ. Patterson

Forsyth Medical Center, WinstonForsyth Medical Center, Winston--Salem, NCSalem, NC 2929

P. OverlieP. Overlie

Lubbock Heart Hospital, Lubbock, TXLubbock Heart Hospital, Lubbock, TX 9595 M. SketchM. Sketch

Duke University Medical Center, Durham, NCDuke University Medical Center, Durham, NC 2828

B. B. McLaurinMcLaurin

Anderson 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. Solomon

Methodist 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. Douglas

Emory Clinic, Atlanta, GAEmory Clinic, Atlanta, GA 5151 R. R. StolerStoler

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

M. BallM. Ball

Heart 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. Caputo

St. Joseph Hospital Health Center, Syracuse, NYSt. Joseph Hospital Health Center, Syracuse, NY 5050 J. SinghJ. Singh

Barnes Jewish, St. Louis, MOBarnes Jewish, St. Louis, MO 2323

A. JainA. Jain

Washington Hospital Healthcare, Fremont, CAWashington Hospital Healthcare, Fremont, CA 4747 D. PintoD. Pinto

Beth Israel Hospital, Boston, MABeth Israel Hospital, Boston, MA 2323

T. T. TollesonTolleson

Mother Francis Health System, Tyler, TXMother Francis Health System, Tyler, TX 4545 B. RutherfordB. Rutherford

St. LukeSt. Luke’’s Hospital, Kansas City, MOs Hospital, Kansas City, MO 2323

B. B. ReenReen

Presbyterian Hospital, Charlotte, NCPresbyterian Hospital, Charlotte, NC 4444 V. V. ChilakamarriChilakamarri

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

H. H. LibermanLiberman

Emory Crawford Long, Atlanta, GAEmory Crawford Long, Atlanta, GA 3636 R. R. PrashadPrashad

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

H. WilsonH. Wilson

Carolinas Medical Center, Charlotte, NCCarolinas Medical Center, Charlotte, NC 3030 T. BassT. Bass

University of Florida, Jacksonville, FLUniversity of Florida, Jacksonville, FL 2020

P. P. BajwaBajwa

Nebraska Heart Institute, Lincoln, NENebraska Heart Institute, Lincoln, NE 2929 T. T. SacchiSacchi

NY Methodist/Cornell Heart Center, Brooklyn, NYNY Methodist/Cornell Heart Center, Brooklyn, NY 2222


Top EnrollersTop Enrollers


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Patient DemographicsPatient DemographicsENDEAVOR IV ENDEAVOR IV ––

3yr FU3yr FU

EndeavorEndeavor(773 pts)(773 pts)

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

Age (in years)Age (in years) 63.5 63.5 ±±

11.111.1 63.6 63.6 ±±

11.011.0 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 Angina ––

Stable (%)Stable (%)

Unstable (%)Unstable (%)

MI (%)MI (%)

45.645.6

51.651.6

2.82.8

47.947.9

49.949.9

2.12.1

0.3670.367


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EndeavorEndeavor(773 lesions)(773 lesions)

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

CAD CAD ––

Single Vessel (%)Single Vessel (%) 54.954.9 57.257.2 0.3840.384Vessel Location (%)Vessel Location (%) 0.7910.791

LADLAD 42.242.2 41.541.5ACC/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 2.73 ±±

0.470.47 2.70 2.70 ±±

0.460.46 0.1970.197

MLD (mm)MLD (mm) 0.96 0.96 ±±

0.400.40 0.93 0.93 ±±

0.400.40 0.1490.149

% DS% DS 64.83 64.83 ±±

13.2913.29 65.68 65.68 ±±

13.1013.10 0.2040.204

Lesion Length (mm)Lesion Length (mm) 13.41 13.41 ±±

5.675.67 13.80 13.80 ±±

6.096.09 0.1990.199

Lesion Characteristics (QCA)Lesion Characteristics (QCA)ENDEAVOR IV ENDEAVOR IV ––

3yr FU3yr FU


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3yr FU3yr FUPatient Flow ChartPatient Flow Chart

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

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

RandomizedRandomized

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

Patients EnrolledPatients EnrolledN = 1548N = 1548

Endeavorn = 773

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

Taxusn = 775


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EndeavorEndeavorn = 734n = 734

TaxusTaxusn = 734n = 734 P P valuevalue

Death (all) Death (all) ––

% (#)% (#) 4.0 (29)4.0 (29) 4.5 (33)4.5 (33) 0.6970.697CardiacCardiac 1.6 (12)1.6 (12) 2.3 (17)2.3 (17) 0.4540.454

MI (all) MI (all) ––

% (#)% (#) 2.2 (16)2.2 (16) 4.9 (36)4.9 (36) 0.0070.007Q WaveQ Wave 0.4 (3)0.4 (3) 0.7 (5)0.7 (5) 0.7260.726Non Q WaveNon Q Wave 1.8 (13)1.8 (13) 4.2 (31)4.2 (31) 0.0090.009

Death (cardiac) + MI (all) Death (cardiac) + MI (all) ––

% (#)% (#) 3.7 (27)3.7 (27) 7.1 (52)7.1 (52) 0.0050.005Stent Thrombosis (def/prob) Stent Thrombosis (def/prob) ––

% (#)% (#) 1.1 (8)1.1 (8) 1.6 (12)1.6 (12) 0.5000.50000--360 days 360 days 0.9 (7)0.9 (7) 0.1 (1)0.1 (1) 0.0700.070361361--1080 days 1080 days 0.1 (1) 0.1 (1) 1.5 (11)1.5 (11) 0.0060.006

TLR TLR ––

% (#)% (#) 6.5 (48) 6.5 (48) 6.0 (44)6.0 (44) 0.7470.747TVR (nonTVR (non--TL) TL) ––

% (#)% (#) 4.8 (35)4.8 (35) 6.8 (50)6.8 (50) 0.1170.117TVR TVR ––

% (#)% (#) 9.9 (73)9.9 (73) 10.9 (80)10.9 (80) 0.6080.608MACE MACE ––

% (#)% (#) 11.4 (84)11.4 (84) 13.8 (101)13.8 (101) 0.2080.208TVF TVF ––

% (#)% (#) 12.4 (91)12.4 (91) 16.1 (118)16.1 (118) 0.0520.052


3yr FU3yr FUClinical Events at 36 monthsClinical Events at 36 months

p-Values were calculated by Fisher’s exact test.ENDEAVOR IV primary endpoint: noninferiority of Endeavor to Taxus at 9 months (target vessel failure).ENDEAVOR IV was not specifically designed or powered to individually compare TLR, MI, CD/MI or VLST.p-Values for outcome differences are unadjusted for multiple comparisons.

Values are the event rates


SA or Japan. ©


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3yr FU3yr FU

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%Cum

ulat

ive

Inci

denc

e fo

r TVF

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

Time after Initial Procedure (days)

1-year HR0.79 [0.56, 1.11]

P = 0.166

9.6%

7.7%

∆∆1.9%1.9%

3-year HR0.76 [0.58, 1.00]

P = 0.049 15.9%

12.3%

∆∆3.6%3.6%

TVF to 36 monthsTVF to 36 monthsEndeavorTaxus

p-Values were calculated by logrank test. p-Values for outcome differences are unadjusted for multiple comparisons.ENDEAVOR IV primary endpoint: noninferiority of Endeavor to Taxus at 9 months (target vessel failure).


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3yr FU3yr FU

12.4%

9.9%

16.1%

7.1%

10.9%

3.7%

Cardiac Death/MI

Rat

e

=

Endeavor (n = 734)Taxus (n = 734)

TVF TVR

P = 0.608

+

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

RRR 23%NNT: 27P = 0.052

RRR 23%NNT: 27P = 0.052

RRR 48%NNT: 29P = 0.005

RRR 48%NNT: 29P = 0.005

Primary EP TVF to 36 monthsPrimary EP TVF to 36 months

Values are the event ratesValues are the event ratesPP values were calculated by Fisher Exact Testvalues were calculated by Fisher Exact Test

p-Values were calculated by logrank test. p-Values for outcome differences are unadjusted for multiple comparisons.ENDEAVOR IV primary endpoint: noninferiority of Endeavor to Taxus at 9 months (target vessel failure).ENDEAVOR IV was not specifically designed or powered to individually compare TLR, MI, CD/MI or VLST


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3yr FU3yr FU

10%

8%

6%

4%

0%

Cum

ulat

ive

Inci

denc

e of

Car

diac

Dea

th/M

I

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

CD/MI to 36 monthsCD/MI to 36 months

Values are the KM estimatesValues are the KM estimates PP values were calculated by Log Rank Testvalues were calculated by Log Rank Test

EndeavorTaxus

p-Values were calculated by logrank test. p-Values for outcome differences are unadjusted for multiple comparisons.ENDEAVOR IV was not specifically designed or powered to individually compare CD/MI.


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CD

/MI (

%)



3yr FU3yr FU

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


CD/MI Landmark to 36 monthsCD/MI Landmark to 36 monthsEndeavorTaxus



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3yr FU3yr FU

0.7%

2.3%

∆∆1.6%1.6%P = 0.017

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

0.60 [0.29, 1.23]2.6%

1.6%

∆∆1.0%1.0%P = 0.154P = 0.154


MI Landmark to 36 monthsMI Landmark to 36 months

MI (

%)


0.0%

1.0%

2.0%

3.0%

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

EndeavorTaxus



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0 0

2

4

0

10

≥≥5X<8X5X<8X ≥≥8X<10X8X<10X ≥≥10X10X

Num

ber P

atie

nts 10/16 (63%) of Taxus MIs

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

with CKMB rises with CKMB rises ≥≥10X ULN 10X ULN

2/4 Endeavor 2/4 Endeavor MIsMIs and 2/16 Taxus and 2/16 Taxus MIsMIs CKMB (CKMB (xULNxULN) <5X) <5X


3yr FU3yr FUAll All MIsMIs CKMB Rises (CKMB Rises (xULNxULN) 1) 1--3 years3 years

Endeavor Taxus



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3yr FU3yr FU

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

DAPT to 36 months*DAPT to 36 months*


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0.1% 0.1%

0.8%0.7%

1.5%

0.0%

Rat

eR

ate

ARC DefiniteARC Definite ARC ProbableARC Probable ARC DefiniteARC DefiniteProbableProbable

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

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

P = 0.006P = 0.006P = 0.006

RRR 91%NNT: 71P = 0.006

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



3yr FU3yr FUARC VLAST 12ARC VLAST 12--36 mos36 mos

Endeavor (n = 734)

Taxus (n = 734)

p-Values were calculated by logrank test. p-Values for outcome differences are unadjusted for multiple comparisons.ENDEAVOR IV was not specifically designed or powered to individually compare VLST. RRR= Relative Risk Reduction


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4%

2%

0%


Cum

ulat

ive

Inci

denc

e of

Def

/Pro

b Th

rom

bosi

sENDEAVOR IV ENDEAVOR IV ––

3yr FU3yr FU

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


ARC ST Def/Prob 12ARC ST Def/Prob 12--36 mos (VLST)36 mos (VLST)EndeavorTaxus

p-Values were calculated by logrank test. p-Values for outcome differences are unadjusted for multiple comparisons.ENDEAVOR IV was not specifically designed or powered to individually compare VLST. RRR= Relative Risk Reduction


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Timing of ARC Def/Prob VLSTTiming of ARC Def/Prob VLSTENDEAVOR IV ENDEAVOR IV ––

3yr FU3yr FU

1080360 480 600 720 840 960

Endeavor VLST (n = 1)Endeavor VLST (n = 1)1/1 No DAPT1/1 No DAPT1/1 Resulted in a MI1/1 Resulted in a MI

369

Endeavor

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 a MI9/11 Resulted in a MI

413495

619645

689697

835838

878949

1024

Taxus

Days

5 Taxus VLST events from 2-3 years

5 Taxus VLST events 5 Taxus VLST events from 2from 2--3 years 3 years


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3yr FU3yr FU

10%

8%

6%

4%

0%Cum

ulat

ive

Inci

denc

e fo

r TLR

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


TLR to 36 monthsTLR to 36 monthsEndeavorTaxus

p-Value was calculated by logrank. p-Values for outcome differences are unadjusted for multiple comparisons.ENDEAVOR IV was not specifically designed or powered to individually compare TLR.


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3yr FU3yr FU

Values are the event ratesValues are the event rates

TLR Rate Over TimeTLR Rate Over TimeTL

R R

ate

1 2 3Years of Follow-up

Endeavor

(Yr 3 N = 734/773)

Taxus

(Yr 3 N = 734/775)

82% Increase44% Increase

4.5%

3.3%

5.9%6.5%

6.0%

4.5%

1 2 3Years of Follow-up

p-Value was calculated by Fisher’s exact test. p-Values for outcome differences are unadjusted for multiple comparisons.ENDEAVOR IV was not specifically designed or powered to individually compare TLR.


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ConclusionsConclusionsLate clinical FU (from 1Late clinical FU (from 1--3 years) from the3 years) from theEndeavor IV RCT demonstrates:Endeavor IV RCT demonstrates:

Endeavor has a significant safety advantage Endeavor has a significant safety advantage compared with Taxuscompared with Taxus; overall, 48% reduction in ; overall, 48% reduction in cardiac death + MI (P=0.004) due to a 91% cardiac death + MI (P=0.004) due to a 91% reduction in VLST from 1reduction in VLST from 1--3 yrs (11 vs. 1 events;3 yrs (11 vs. 1 events;

PP = 0.004). The VLST frequency of Endeavor = 0.004). The VLST frequency of Endeavor (0.1%) is similar to a bare metal stent.(0.1%) is similar to a bare metal stent.

Endeavor @ 3 years, reduced TVF, by 23%, from Endeavor @ 3 years, reduced TVF, by 23%, from 15.9% to 12.3% (15.9% to 12.3% (PP = 0.049)= 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.

p-Values were calculated by Fisher’s exact test.ENDEAVOR IV primary endpoint: noninferiority of Endeavor to Taxus at 9 months (target vessel failure).ENDEAVOR IV was not specifically designed or powered to individually compare TLR, MI, CD/MI or VLST.p-Values for outcome differences are unadjusted for multiple comparisons.


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Medtronic Vascular3576 Unocal PlaceSanta Rosa, CA 95403 USATel: +1.707.525.0111www.Medtronic.comwww.EndeavorStent.com

Medtronic BV Earl Bakkenstraat 10 6422 PJ Heerlen The Netherlands Tel: +31.45.566.8000 Fax: +31.45.566.8668

endeavor iv · endeavor iv – 3yr fu. single . de novode novo . native coronary lesion vessel...

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