ENDEAVOR IV ENDEAVOR IV Two-Year Follow-up from a Prospective - - PowerPoint PPT Presentation

Martin B. Leon, MD for the Endeavor IV investigators

Columbia University Medical Center Columbia University Medical Center Cardiovascular Research Foundation Cardiovascular Research Foundation New York City New York City

Tuesday, October 14, 2008 Tuesday, October 14, 2008

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

ENDEAVOR IV ENDEAVOR IV

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 µ g per mm stent length

ENDEAVOR IV – 2yr FU ENDEAVOR IV – 2yr FU

Single Single De Novo De Novo Native Coronary Lesion Native Coronary Lesion Vessel Diameter: 2.5–3.5 mm Vessel Diameter: 2.5–3.5 mm Lesion Length: ≤ 27 mm Lesion Length: ≤ 27 mm Pre-dilatation required Pre-dilatation required 30d 6mo 4yr 3yr 2yr 9mo 12mo 8mo 5yr Clinical/MACE Clinical/MACE Angiography/IVUS Angiography/IVUS

QCA and IVUS QCA and IVUS Subset Subset (328 total = 21.2%) (328 total = 21.2%)

Clinical Trial Design Clinical Trial Design

PI: Martin B. Leon PI: Martin B. Leon

1:1 randomization N = 1,548 patients 80 sites US

Endeavor Stent n = 774 Taxus Stent n = 774

625 633 642 660 690 717 738 755 775 Taxus 635 645 653 674 700 736 749 769 773 Endeavor

15% 10% 5% 0% 90 180 270 360 450 540 630 720 Time after Initial Procedure (days) Cumulative Incidence for TVF

Endeavor Taxus

9.5% 7.7% 13.1% 11.1% 1-year HR 0.79 [0.56, 1.12] P = 0.188 2-year HR 0.83 [0.62, 1.12] P = 0.220 ∆ ∆1.8% 1.8% ∆ ∆2.0% 2.0%

ENDEAVOR IV – 2yr FU ENDEAVOR IV – 2yr FU TVF to 24 months (1 TVF to 24 months (1ry

ry endpt)

endpt)

90 180 270 360 450 540 630 720 Time after Initial Procedure (days) Cumulative Incidence for TLR

Endeavor Taxus

3.2% 4.5% 4.7% 6.0% 1-year HR 1.42 [0.84, 2.39] P = 0.188 2-year HR 1.30 [0.83, 2.04] P = 0.255 ∆ ∆1.3% 1.3% ∆ ∆1.3% 1.3%

660 663 668 687 708 740 757 771 775 Taxus 654 661 666 684 706 744 755 773 773 Endeavor

15% 10% 5% 0%

ENDEAVOR IV – 2yr FU ENDEAVOR IV – 2yr FU TLR to 24 months TLR to 24 months

1.5% 0.4% 1.6% 3.4% 1.2% 4.1% 0.5% 3.5% 5.1% 2.0%

Non-Q Non-Q Rate Rate

P =0.725 P =0.725 P =0.823 P =0.823 P =0.022 P =0.023

MI All MI All Q-wave Q-wave

Endeavor (n=742) Taxus (n=739)

Cardiac Cardiac Death Death Cardiac Death Cardiac Death and MI and MI

P =0.096 P =0.096

ENDEAVOR IV – 2yr FU ENDEAVOR IV – 2yr FU Safety Endpoints to 24 months Safety Endpoints to 24 months

0.1% 0.4% 0.1% 0.7% 0.1% 0.3% 0.8% 0.0%

Rate Rate

Endeavor (n=742) Taxus (n=739)

ARC Definite ARC Definite ARC Probable ARC Probable ARC Definite ARC Definite Probable Probable ARC Possible ARC Possible

n=5 n=6 n=1 n=1 n=1 n=2 n=3 P =0.124 P =0.124 P =0.499 P =0.499 P =1.000 P =1.000 P =0.069 P =0.069

ENDEAVOR IV – 2yr FU ARC ST 12-24 mos

ASA + Clopidogrel QMI 697 Probable TAXUS None QMI 369 Definite Endeavor ASA + Clopidogrel NQMI 689 Definite TAXUS ASA Only QMI 645 Definite TAXUS ASA + Clopidogrel NQMI 619 Definite TAXUS ASA + Clopidogrel NQMI 495 Definite TAXUS ASA Only QMI 413 Definite TAXUS

DAPT at event Clinical Event Time (Days) Definite/ Probable DES

ENDEAVOR IV – 2yr FU ARC Def/Prob ST 12-24 mos (VLST)

720 360 450 540 630 Cumulative Incidence of MI 360 2% 1% 0% 450 540 630 720 699 703 706 725 725 Tax 699 705 709 726 726 End 697 702 706 725 725 Tax 697 703 707 726 726 End Def/Prob Thrombosis (ARC) 2% 1% 0%

ARC Definite/Probable ST Myocardial Infarction

Endeavor Taxus Endeavor Taxus 1-2year P = 0.11 1-2year P = 0.06

ENDEAVOR IV – 2yr FU ARC Def/Prob ST and MI 12-24 mos

Days after procedure Days after procedure

2 413 495 619 645 689 697 1 2 2 83 130 145 171 369

60 120 180 240 300 360 420 480 540 600 660 720

ENDEAVOR IV – 2yr FU Timing of ARC Def/Prob ST

Endeavor Endeavor Taxus Taxus

60 120 180 240 300 360 420 480 540 600 660 720

Endeavor Endeavor Taxus Taxus

2 495 619 689 697 413 645 145 1 2 2 83 130 171 369*

20 53 10 * Off both ASA and Clopidogrel 43

ENDEAVOR IV – 2yr FU Timing of ARC Def/Prob ST

Days after procedure Days after procedure Off DAPT Off DAPT

ENDEAVOR IV In Perspective ARC Def/Prob ST Landmark Analysis

Endeavor Pooled 2068 2036 1650 1087 Endeavor EIV 739 693 NA NA

1 Yr 2 Yrs 3 Yrs 4 Yrs

ARC (ef/Prob ST Days

0.0% 0.5% 1.0% 1.5% 2.0% 2.5% 360 720 1080 1440

0.9% 0.9% 0.1% 0.1% 0.6% 0.6%

95% CI 95% CI [0.00-0.95] [0.00-0.95]

0.1% 0.1% 0.1% 0.1% 0.1% 0.1%

95% CI 95% CI [0.00-0.25] [0.00-0.25] 95% CI 95% CI [0.00-0.29] [0.00-0.29] 95% CI 95% CI [0.00-0.32] [0.00-0.32]

• Efficacy

Efficacy

• Continued similar TLR and TVR, even in high

Continued similar TLR and TVR, even in high restenosis risk subgroups (e.g. diabetics) and restenosis risk subgroups (e.g. diabetics) and especially in the patients with only clinical FU especially in the patients with only clinical FU

• Safety

Safety

• Reduced ARC def/prob very late stent

Reduced ARC def/prob very late stent thrombosis (P=0.059; 1 vs. 6 events), even in thrombosis (P=0.059; 1 vs. 6 events), even in the setting of frequent DAPT use the setting of frequent DAPT use

• Reduced all MIs (P=0.023), linked to the

Reduced all MIs (P=0.023), linked to the decrease in very late stent thrombosis events decrease in very late stent thrombosis events

• Safety findings consistent with the larger

Safety findings consistent with the larger pooled analysis of Endeavor studies pooled analysis of Endeavor studies

ENDEAVOR IV – 2yr FU ENDEAVOR IV – 2yr FU Conclusions Conclusions

Between 12 and 24 mos FU, the Endeavor DES, Between 12 and 24 mos FU, the Endeavor DES, compared with the Taxus DES, demonstrated… compared with the Taxus DES, demonstrated…