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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
ve In
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
ve In
cid
ence
of
Car
dia
c D
eath
/MI
0 90 180 270 360 450 540 630 720 810 900 990 1080
Time after Initial Procedure (days)
2%
EndeavorEndeavor 773773 769769 754754 747747 734734 720720 706706 703703 697697 685685 673673 669669 666666
TaxusTaxus 775775 758758 747747 738738 727727 715715 702702 698698 693693 678678 667667 658658 650650
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 HR0.66 [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 (
%)
Time after Initial Procedure (days)
ENDEAVOR IV – 3yr FUENDEAVOR IV – 3yr FUCD/MI Landmark to 36 monthsCD/MI Landmark to 36 months
EndeavorTaxus
Values are the KM estimatesValues are the KM estimatesPP values were calculated by Log Rank Test values were calculated by Log Rank Test
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 (
%)
Time after Initial Procedure (days)
EndeavorTaxus
Values are the KM estimatesValues are the KM estimatesPP values were calculated by Log Rank Test values were calculated by Log Rank Test
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%
Time after Initial Procedure (days)
Cu
mu
lati
ve In
cid
ence
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
Values are the KM estimatesValues are the KM estimatesPP values were calculated by Log Rank Test values were calculated by Log Rank Test
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
lati
ve In
cid
ence
fo
r T
LR
0 90 180 270 360 450 540 630 720 810 900 990 1080
Time after Initial Procedure (days)
2%
EndeavorEndeavor 773773 773773 755755 744744 706706 690690 676676 672672 665665 651651 639639 635635 630630
TaxusTaxus 775775 771771 758758 742742 712712 695695 682682 677677 674674 659659 646646 635635 628628
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 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]
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
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]
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
0.740.74 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
Time after Initial Procedure (days)
Endeavor Taxus
6%
8%
12%
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Dea
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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
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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%
After 1 year After 1 year Endeavor: 1.6%Endeavor: 1.6%Driver: 3.3%Driver: 3.3%
Cu
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Car
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MI
360 720 1080 14400%
0
15%
EndeavorEndeavor 21322132 21022102 20082008 19491949 16431643 10851085
% 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%
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.
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
Before 1 yearBefore 1 yearEndeavor: 2.8%Endeavor: 2.8%Driver: 4.5%Driver: 4.5%
Before 1 yearBefore 1 yearEndeavor: 2.8%Endeavor: 2.8%Driver: 4.5%Driver: 4.5%
After 1 year After 1 year Endeavor: 2.7%Endeavor: 2.7%Driver: 4.0%Driver: 4.0%
After 1 year After 1 year Endeavor: 2.7%Endeavor: 2.7%Driver: 4.0%Driver: 4.0%
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
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Def
/Pro
b T
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mb
osi
s
360 720 1080 14400%
0
4%
EndeavorEndeavor 21322132 21312131 20432043 19871987 16811681 11161116
% 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%
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.
3%
2%
1800
1%
Endeavor Driver
0.8%
1.7%
Before 1 yearBefore 1 yearEndeavor: 0.6%Endeavor: 0.6%Driver: 1.3%Driver: 1.3%
Before 1 yearBefore 1 yearEndeavor: 0.6%Endeavor: 0.6%Driver: 1.3%Driver: 1.3%
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)