Three-Year Follow-up from a Prospective Randomized Trial Comparing a Zotarolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease - PowerPoint PPT Presentation

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Three-Year Follow-up from a Prospective Randomized Trial Comparing a Zotarolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease

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Title: Three-Year Follow-up from a Prospective Randomized Trial Comparing a Zotarolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease


1
Three-Year Follow-up from a Prospective
Randomized Trial Comparing a Zotarolimus-Eluting
Stent and a Paclitaxel-Eluting Stent in Patients
with Coronary Artery Disease
ENDEAVOR IV
Martin B. Leon, MD for the Endeavor IV
investigators
Columbia University Medical Center Cardiovascular
Research Foundation New York City
Monday, September 22, 2009
2
ENDEAVOR IV 3yr FU
Clinical Trial Design PIs Martin B. Leon and
David E Kandzari
Single De Novo Native Coronary Lesion Vessel
Diameter 2.53.5 mm Lesion Length 27
mm Pre-dilatation required
11 randomization N 1,548 patients 80 sites US
Endeavor Stent n 774
Taxus Stent n 774
Clinical/MACE
30d
6mo
4yr
3yr
2yr
9mo
12mo
8mo
5yr
Angiography/IVUS
QCA and IVUS Subset (328 total 21.2)
Primary Endpoint TVF at 9 months Secondary
Endpoints In-segment DS at 8 months TLR and
TVR at 9 months Drug Therapy ASA and
Clopidogrel/Ticlid 6 months Zotarolimus Dose 10
?g per mm stent length
3
Endeavor IV - Top Enrollers
Patients Patients
C. OShaughnessy Elyria Memorial Hospital, Elyria, OH 119 J. Patterson Forsyth Medical Center, Winston-Salem, NC 29
P. Overlie Lubbock heart Hospital, Lubbock, TX 95 M. Sketch Duke University Medical Center, Durham, NC 28
B. McLaurin Anderson Medical Center, Anderson, SC 63 M. Leon Columbia Presbyterian Center NY, NY, NY 28
S. Solomon Methodist Hospital Houston, Houston, TX 59 P. Coleman Sutter Medical Center, Santa Rosa, CA 27
J. Douglas Emory Clinic, Atlanta, GA 51 R. Stoler Baylor Heart Vascular, Dallas, TX 26
M. Ball Heart Center of Indiana, Indianapolis, IN 51 S. Papadakos New York Hospital of Queens, Flushing, NY 26
R. Caputo St. Joseph Hospital health Center, Syracuse, NY 50 J. Singh Barnes Jewish, St. Louis, MO 23
A. Jain Washington Hospital Healthcare, Fremont, CA 47 D. Pinto Beth Israel Hospital, Boston, MA 23
T. Tolleson Mother Francis health System, Tyler, TX 45 B. Rutherford St. Lukes Hospital, Kansas City, MO 23
B. Reen Prsbyterian hospital, Charlotte, NC 44 V. Chilakamarri Lutheran Hospital of IN, Fort Wayne, IN 22
H. Liberman Emory Crawford Long, Atlanta, GA 36 R. Prashad Ocala Regional Medical Center, Ocala, FL 22
H. Wilson Carolinas Medical Center, Charlotte, NC 30 T. Bass University of Florida, Jacksonville, FL 22
P. Bajwa Nebraska Heart Institute, Lincoln, NE 29 T. Sacchi NY Methodist/Cornell Heart Center, Brooklyn, NY 20
4
ENDEAVOR IV 3yr FU Patient Demographics
Endeavor (773 pts) Taxus (775 pts) P value
Age (in years) 63.5 11.1 63.6 11.0 0.930
Men () 66.9 68.5 0.514
Diabetes () 31.2 30.5 0.783
IDDM () 10.3 8.3 0.162
Prior MI () 21.1 23.2 0.324
Angina Stable () Unstable () MI () 45.6 51.6 2.8 47.9 49.9 2.1 0.367
5
ENDEAVOR IV 3yr FU Lesion Characteristics (QCA)
Endeavor (773 lesions) Taxus (775 lesions) P value
CAD Single Vessel () 54.9 57.2 0.384
Vessel Location () 0.791
LAD 42.2 41.5
ACC/AHA Lesion Class 0.358
B2/C 69.6 70.9
QCA
RVD (mm) 2.73 0.47 2.70 0.46 0.197
MLD (mm) 0.96 0.40 0.93 0.40 0.149
DS 64.83 13.29 65.68 13.10 0.204
Lesion Length (mm) 13.41 5.67 13.80 6.09 0.199
6
ENDEAVOR IV 3yr FU Patient Flow Chart
7
ENDEAVOR IV 3yr FU TVF to 36 months
3-year HR 0.77 0.58, 0.99 P 0.049
20
1-year HR 0.79 0.56, 1.11 P0.166
15.9
15
?3.6
9.6
12.3
10
Cumulative Incidence for TVF
7.7
5
?1.9
0
0
90
180
270
360
450
540
630
720
810
900
990
1080
Time after Initial Procedure (days)
Endeavor 773 769 749 736 700 680 662 655 645 633 620 615 610
Taxus 775 755 739 719 694 668 656 647 639 621 607 596 589
Values are the KM estimates P values were
calculated by Log Rank Test
8
ENDEAVOR IV 3yr FU Primary EP TVF to 36 months
P 0.608
Rate
91/734
118/734
73/734
27/734
52/734
80/734
Cardiac Death/MI

TVF
TVR

Values are the event rates P values were
calculated by Fisher Exact Test
9
ENDEAVOR IV 3yr FU CD/MI to 36 months
3-year HR 0.52 0.32, 0.82 P 0.004
10
1-year HR 0.66 0.35, 1.25 P0.201 ?1.0
8
7.1
6
Cumulative Incidence of Cardiac Death/MI
?3.5
3.1
4
2
3.6
2.1
0
0
90
180
270
360
450
540
630
720
810
900
990
1080
Time after Initial Procedure (days)
Endeavor 773 769 754 747 734 720 706 703 697 685 673 669 666
Taxus 775 758 747 738 727 715 702 698 693 678 667 658 650
Values are the KM estimates P values were
calculated by Log Rank Test
10
ENDEAVOR IV 3yr FU CD/MI Landmark to 36 months
6.0
4.0
CD/MI ()
2.0
0.0
0
90
180
270
360
450
540
630
720
810
900
990
1080
Time after Initial Procedure (days)
Values are the KM estimates P values were
calculated by Log Rank Test
11
ENDEAVOR IV 3yr FU MI Landmark to 36 months
3.0
2.0
MI ()
1.0
0.0
0
90
180
270
360
450
540
630
720
810
900
990
1080
Time after Initial Procedure (days)
Values are the KM estimates P values were
calculated by Log Rank Test
12
ENDEAVOR IV 3yr FU All MIs CKMB Rises (xULN)
1-3 years
10/16 (63) of Taxus MIs with CKMB rises ?10X
ULN
Number Patients
10X
5Xlt8X
8Xlt10X
2/4 Endeavor MIs and 2/16 Taxus MIs CKMB (xULN)
lt5X
13
ENDEAVOR IV 3yr FU DAPT to 36 months
Length of DAPT Endeavor Taxus P value
180 days on () 92.1 91.4 0.639
270 days on () 54.5 54.5 1.000
360 days on () 57.6 57.2 0.873
720 days on () 65.4 71.3 0.019
1080 days on () 48.2 52.1 0.174
Physicians and patients unblinded at 12 months
14
ENDEAVOR IV 3yr FU ARC VLST 12-36 mos
P 0.006
RRR 91 NNT 71 P0.006
P 0.124
P 0.062
Rate
n6
n5
n1
n11
n1
ARC Definite Probable
ARC Definite
ARC Probable
Values are the event rates P values were
calculated by Fisher Exact Test
15
ENDEAVOR IV 3yr FU ARC ST Def/Prob 12-36 mos
(VLST)
4
1-3 year HR 0.09 0.01, 0.71 P 0.004
Cumulative Incidence of Def/Prob Thrombosis
2
1.6
?1.5
0.1
0
Time after Initial Procedure (days)
Endeavor 732 732 719 716 710 699 688 684 680
Taxus 734 734 721 718 714 701 690 681 674
Values are the KM estimates P values were
calculated by Log Rank Test
16
ENDEAVOR IV 3yr FU Timing of ARC Def/Prob VLST
5 Taxus VLST events from 2-3 years
Taxus
Endeavor
360
480
600
720
840
960
1080
Days
17
ENDEAVOR IV 3yr FU TLR to 36 months
3-year HR 1.10 0.73, 1.65 P 0.662
10
1-year HR 1.36 0.81, 2.28 P0.239
8
6.5
6
4.5
6.1
Cumulative Incidence for TLR
4
?0.4
3.3
2
?1.2
0
0
90
180
270
360
450
540
630
720
810
900
990
1080
Time after Initial Procedure (days)
Endeavor 773 773 755 744 706 690 676 672 665 651 639 635 630
Taxus 775 771 758 742 712 695 682 677 674 659 646 635 628
Values are the KM estimates P values were
calculated by Log Rank Test
18
ENDEAVOR IV 3yr FU TLR Rate Over Time
Taxus (Yr 3 N 734/775)
Endeavor (Yr 3 N 734/773)
TLR Rate
1
2
3
1
2
3
Years of Follow-up
Years of Follow-up
Values are the event rates
19
Endeavor II and Taxus IV DES Arms TLR Rates to
5 years
ENDEAVOR II (n577/598)
TAXUS IV (n618/662)
TLR ()
TLR ()
1
2
3
4
5
1
2
3
4
5
Years of Follow-up
Years of Follow-up
5 Year Clinical Results of TAXUS IV, Stone, ACC
2007 Results come from separate clinical trials.
Data may differ in a head-to-head comparison.
20
Subgroup Post-Hoc Analysis
  • ENDEAVOR IV

21
ENDEAVOR IV 3yr FU TVF (36 mos) Post Hoc
Analysis
Risk Ratio 95 CI
P-Value Interaction
Risk Ratio
Endeavor
Taxus
Diabetes Non-diabetes
0.80 15.6 (35) 21.6 (47) 0.659
0.72 11.0 (56) 13.8 (71)
RVD ?2.5mm gt2.5 lt3.0mm ?3.0mm
0.60 11.8 (29) 19.8 (51) 0.278
0.96 13.8 (40) 14.4 (41)
0.82 11.2 (22) 13.7 (26)
Lesion Length ?10mm gt10 lt20mm ?20mm
0.55 10.1 (23) 18.6 (41) 0.799
0.95 13.6 (57) 14.4 (58)
0.66 11.5 (10) 17.4 (19)
0.82 12.0 (82) 14.7 (95) 0.743
0.73 18.6 (8) 25.3 (71)
Single Stent Multiple Stents OVERALL
0.77 12.4 (99) 16.1 (118)
Pdiff0.052
Favors Endeavor
Favors Taxus
1
10
0.1
TVF (Target Vessel Failure) is defined as cardiac
death, MI or TVR
22
ENDEAVOR IV 3yr FU CD/MI (36 mos) Post Hoc
Analysis
Risk Ratio 95 CI
P-Value Interaction
Risk Ratio
Endeavor
Taxus
Diabetes Non-diabetes
0.36 2.7 (6) 7.3 (16) 0.376
0.59 4.1 (21) 7.0 (36)
RVD ?2.5mm gt2.5 lt3.0mm ?3.0mm
0.26 2.0 (5) 7.8 (20) 0.143
0.76 4.8 (14) 6.3 (18)
0.55 4.1 (8) 7.4 (14)
Lesion Length ?10mm gt10 lt20mm ?20mm
0.22 1.8 (4) 8.1 (18) 0.887
0.81 5.0 (21) 6.2 (25)
0.28 2.3 (2) 8.3 (9)
Single Stent Multiple Stents OVERALL
0.56 3.7 (25) 6.5 (42) 0.615
0.39 4.7 (2) 12.0 (9)
0.52 3.7 (27) 7.1 (52)
Pdiff0.005
Favors Endeavor
Favors Taxus
1
10
0.1
23
ENDEAVOR IV 3yr FU TVR (36 mos) Post Hoc
Analysis
Risk Ratio 95 CI
P-Value Interaction
Risk Ratio
Endeavor
Taxus
Diabetes Non-diabetes
0.92 14.3 (32) 15.6 (34) 0.978
0.90 8.0 (41) 8.9 (46)
RVD ?2.5mm gt2.5 lt3.0mm ?3.0mm
0.74 10.6 (26) 14.3 (37) 0.191
0.98 10.0 (29) 10.2 (29)
1.24 9.1 (18) 7.4 (14)
Lesion Length ?10mm gt10 lt20mm ?20mm
0.66 9.3 (21) 14.0 (31) 0.923
1.06 10.3 (43) 9.7 (39)
1.00 9.2 (8) 9.2 (10)
1.01 9.7 (66) 9.6 (62) 0.524
0.75 14.0 (6) 18.7 (14)
Single Stent Multiple Stents OVERALL
0.98 9.9 (73) 10.9 (80)
Pdiff0.608
Favors Endeavor
Favors Taxus
1
10
0.1
24
Diabetics
Endeavor IV
25
ENDEAVOR IV 3yr FU Diabetics Efficacy Endpoints
to 36 months
P 0.113
P 0.347
P 0.790
P 0.744
Rate
22/224
19/218
35/224
32/224
34/218
47/218
29/224
36/218
MACE
TLR
TVF
TVR
Values are the event rates
P values were calculated by Fisher Exact Test
26
ENDEAVOR IV 3yr FU Diabetics Safety Endpoints
to 36 months
P 0.029
P 0.084
P 0.136
P 0.216
Rate
P 0.493
3/224
9/218
13/224
9/218
1/218
3/224
7/218
6/224
16/218
Non-Q
MI All
Q-wave
Cardiac Death
Cardiac Death and MI
Values are the event rates
P values were calculated by Fisher Exact Test
27
ENDEAVOR IV 3yr FU Diabetics CD/MI to 36 months
14
12
10
8
Cumulative Incidence of Cardiac Death or MI
6
4
2
0
0
90
180
270
360
450
540
630
720
810
900
990
1080
Time after Initial Procedure (days)
Endeavor 241 241 236 233 230 227 220 220 220 215 209 206
Taxus 236 234 231 228 223 220 216 214 213 207 202 198
28
Program Consistency
Endeavor IV
29
Endeavor Randomized Clinical Trials CD/MI at
Latest Available Follow-up
HR 95CI 1.28 0.85-1.92 P0.265
HR 95CI 4.19 1.20-14.6 P0.024 NNH24
HR 95CI 1.93 1.22-3.03 P0.005 NNH29
49/582
38/577
6/110
4/307
52/734
27/734
Endeavor II to 5 years
Endeavor III to 4 years
Endeavor IV to 3 years
30
Endeavor Randomized Clinical Trials TLR at Latest
Available Follow-up
HR 95CI 2.19 2.56-3.08 Plt0.001 NNT11
HR 95CI 0.81 0.36-1.84 P0.832
HR 95CI 0.92 0.62-1.36 P0.747
95/582
43/577
7/110
24/307
44/734
48/734
Endeavor II to 5 years
Endeavor III to 4 years
Endeavor IV to 3 years
31
Endeavor Clinical Program Pooled Safety and
Efficacy Analyses
Premarket Safety and Efficacy Package
1yr 2yr 3yr 4yr 5yr
ENDEAVOR I
Single Arm First-in-Man (n 100)
5yr
ENDEAVOR II
11 RCT vs. BMS (E 598,D 599) PK (n 106)
5yr
ENDEAVOR II CA
Continued Access Single Arm (n 296)
4yr
ENDEAVOR III
31 RCT vs. Cypher (E 323,C 113)
4yr
ENDEAVOR IV
11 RCT vs. Taxus (E 773,T 775)
3yr
ENDEAVOR PK
Pharmacokinetic Study (n 43)
3yr
ENDEAVOR Japan
Single Arm (n 99)
2yr
Included in Pooled Safety and Efficacy Analyses
(N2132)
32
Endeavor Clinical Program Pooled DAPT Compliance
to 5 yrs
Endeavor E I, E II, EII CA, E III, E IV (n
2132)
96
DAPT1 E I, E II, E II CA, E III was 3 months
76
DAPT1 E IV was 6 months
Adherence to DAPT ()
39
31
24
8
8
Days
1. Protocol requirement DAPT 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.
33
Endeavor Pooled Efficacy Analysis Cumulative
Incidence of TLR to 5 years
16.5
Cumulative Incidence of TLR
7.0
0
360
720
1080
1440
0
1800
Time After Initial Procedure (days)
Endeavor 2132 2130 1907 1840 1547 1030
CI 0.09 5.43 6.23 6.75 6.84 6.95
Driver 596 595 489 474 456 445
CI 0.17 13.16 14.23 14.78 15.91 16.49
Values are the KM estimates. P-values were
calculated by Log Rank Test.
34
ENDEAVOR Pooled Safety Analysis Cumulative
Incidence of CD/MI to 5 years
8.4
Cumulative Incidence of Cardiac Death or MI
5.4
0
360
720
1080
1440
0
1800
Time After Initial Procedure (days)
Endeavor 2132 2102 2008 1949 1643 1085
CI 1.41 2.83 3.42 3.77 4.42 5.42
Driver 596 581 555 544 529 523
CI 2.52 4.54 5.75 6.62 6.98 8.42
Values are the KM estimates. P-values were
calculated by Log Rank Test.
35
Endeavor Pooled Safety Analysis ARC
Definite/Probable ST to 5 years
Cumulative Incidence of Def/Prob Thrombosis
1.7
0.8
0
360
720
1080
1440
0
1800
Time After Initial Procedure (days)
Endeavor 2132 2131 2043 1987 1681 1116
CI 0.05 0.62 0.71 0.71 0.80 0.80
Driver 596 595 570 559 543 538
CI 0.17 1.35 1.35 1.52 1.52 1.71
Values are the KM estimates. P-values were
calculated by Log Rank Test.
36
Conclusions Endeavor IV
  • Late clinical FU (from 1-3 years) from
    the Endeavor IV RCT demonstrates
  • Endeavor has a significant safety advantage cw
    Taxus overall, 48 reduction in cardiac death
    MI (P0.004) due to a 91 reduction in VLST from
    1-3 yrs (11 vs. 1 events P0.004). The VLST
    frequency of Endeavor (0.1) is similar to a bare
    metal stent.
  • Endeavor _at_ 3 years, reduced TVF, the 1ry study
    endpoint, by 23, from 15.9 to 12.3 (P0.049)
  • Overall TLR _at_ 3 years was similar (Endeavor 6.5
    vs. Taxus 6.0) with a trend suggesting less late
    TLR (after 1 year) associated with Endeavor.

37
Conclusions Endeavor Program
  • In More than 2100 patients studied with over 1000
    patients now out to 5 years in pooled analysis
  • Low 7 TLR at 5 years in more than 1000 patients
    in ENDEAVOR Pooled Analysis
  • Despite only 39 of patients on DAPT at 1 year in
    ENDEAVOR Pooled Analysis1
  • Low 0.8 ST2 to 5 years (BMS 1.7, p 0.061)
  • Extremely low 0.2 VLST2 after 1 year through 5
    years
  • Significant reduction in CD/MI vs. BMS at 5 years
    (Endeavor 5.5 vs. BMS 8.4, p 0.009)
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