The Detrimental Impact of Chronic Renal Insufficiency

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					 Endeavor IV: A Randomized
Comparison of a Zotarolimus-
Eluting Stent and a Paclitaxel-
Eluting Stent in Patients with
   Coronary Artery Disease

    Martin B. Leon, MD
 Columbia University Medical Center
 Cardiovascular Research Foundation
           New York City

         Monday, October 22, 2007
 Presenter Disclosure Information
for TCT 2007; October 20-25, 2007


  Martin B. Leon, M.D.

    Scientific Advisory Board:
Medtronic Vascular, Abbott Vascular,
Cordis-JNJ, and Boston Scientific
   Endeavor DES System
Driver Cobalt Alloy Stent   Stent Delivery System




   PC Technology             Drug: Zotarolimus
    Polymer and Drug Matrix
     PC Basecoat                             Drug Layer
     (≈ 1μm thick)                           90% Zotarolimus (10μg/mm)
                                             10% PC (≈ 2-4μm thick)

                                                    PC Overspray
          Tissue                                    (≈ 0.1 μm thick)
                                Stent
                                Strut
          Blood                              Illustrative
                                             Not to Scale




3.0 mm Stents
500x magnification

                     Endeavor           Cypher              Taxus
Porcine Drug Elution Kinetics and PK
                          Drug Elution by Recovered Drug from Stent

                              100            87                                     99                                             • Zotarolimus is
% Drug Eluted




                                                                     98
                              75        65                                                                                           hydrophobic and
                              50                                                                                                     rapidly elutes from
                              25                                                                                                     the hydrophilic PC
                               0
                                                                                                                                     polymer matrix within
                                    0            5        10
                                                          Time (Days)
                                                                      15        20        25                                         14 days
                          Blood and Arterial Tissue Zotarolimus Concentration
                                                                                                                                   • Zotarolimus is highly

                                                                                                    Concentration (Tissue) ng/ml
Concentration (Blood) ng/ml




                               4                                           Blood               30
                                                                           Tissue                                                    lipophilic enabling
                               3
                                                                                               20                                    rapid arterial tissue
                               2                                                                                                     loading and drug
                                                                                               10
                               1                                                                                                     retention which is
                               0                                                               0                                     sustained for ~28 days
                                    0        5       10         15         20        25   30
                                                               Days
Biocompatibility (Inflammation Scores)
    Porcine inflammation scores show mild response to a 3X overdose
    (30μg/mm) and 6X overdose (overlapping 30μg/mm) at all chronic time
    points up to 180 days with single and overlapped stents.


                                Inflammation Scores1                                                          Inflammation Scores1
                                    28 to 180 days                                                                28 to 180 days
                       3                                                                             3
                                                                 Driver                                                                   Driver OL




                                                                               Inflammation Scores
 Inflammation Scores




                                                                 Endeavor 3X                                                              Endeavor 3X OL
                       2                                                                             2



                                             *                                                                                *
                       1                                                                             1
                                                             *                                                                         *
                               ND2                                                                           ND2
                       0                                                                             0
                           n             7   9          4    4     5   8                                 n              6 9          4 7        5 7
                                7          28               90      180                                       7          28          90          180
                                                 Days                                                                         Days
                           1 Bare stent controls matched with test groups                                1 Bare stent controls matched with test groups
                           2 Not Done                                                                    2 Not Done
                           *P<0.05 compared to the respective controls                                   *P<0.05 compared to the respective controls


                                                                 *CVPath, Dr Renu Virmani
                                          Endothelial Coverage
                      Porcine histology and SEM show rapid endothelial
                      replacement with both single and overlapping (OL) stents*.
                           Percent Endothelialization1                                                           Percent Endothelialization1
                                 7 to 180 days                                                                         7 to 180 days
                     100                                                                             100
                                                                        Endeavor                                                                                Endeavor OL




                                                                                     % Endotheliazation
% Endotheliazation




                                                                        Driver                                                                                  Driver OL
                     75                                                                                   75
                                                                                                                  *
                     50                                                                                   50


                     25                                                                                   25


                       0                                                                                   0
                               7          28          90         180                                                  7       28           90         180
                                               Days                                                                                Days
                            FS102       FS99       FS100       FS11         Study                                FS102       FS99       FS100       FS11        Study
                                                                            Number                                                                              Number
                           1 Bare stent controls matched with test groups                                      1 Bare stent controls matched with test groups
                                                                                                               *P<0.05 compared to respective controls

                                    Single Stents                                                              Overlapping (OL) Stents
                                                                *CVPath, Dr Renu Virmani
     Preserved Endothelial Function
In Vivo Assessment of Endothelial Function
     in Porcine Models: eNOS Staining

      Immunohistochemistry Staining for Presence of eNOS

  Driver                          Endeavor
            Preserved Endothelial Function
             In Vivo Assessment of Endothelial Function
                 Porcine Model: Active Vasoreactivity
      Distal Vessel Vasoreactivity Following Acetylcholine (Ach) Challenge
       mm
                   Driver                   mm
                                                     Endeavor
      4.5                                       4.5




       3                                         3




      1.5                                       1.5
28d          Baseline     Ach   (10-5M)   28d         Baseline   Ach (10-5M)

        mm                                      mm
      4.5                                       4.5




       3                                         3




      1.5                                       1.5
90d          Baseline     Ach   (10-5M)   90d         Baseline   Ach (10-5M)
   Endeavor Clinical Program Overview
              Premarket Safety and Efficacy Package
                                                              9m 2yr 3yr 4yr
ENDEAVOR I         Single Arm First-in-Man (n=100)                        4yr
ENDEAVOR II        1:1 RCT vs. BMS (E=598,D=599) PK (n=106)               3yr

ENDEAVOR II CA     Continued Access Single Arm (n=296)              2yr
ENDEAVOR III       3:1 RCT vs. Cypher® (E=323,C=113)                2yr
ENDEAVOR IV        1:1 RCT vs.Taxus® (E=773,T=775)        12mo
ENDEAVOR PK        Pharmacokinetic Study (n=43)               9mo
ENDEAVOR Japan     Single Arm (n=99)                          9mo

                               Ongoing
                   1:1 RCT vs. Cypher (E=4400,C=4400)
PROTECT
E-FIVE             Open Label Single Arm (n=8000)

                               Proposed
US Post Approval   Open Label Single Arm Study (n=2000)
   Endeavor Clinical Program Overview
              Premarket Safety and Efficacy Package
                                                               9m 2yr 3yr 4yr
ENDEAVOR I          Single Arm First-in-Man (n=100)                        4yr
ENDEAVOR II         1:1 RCT vs. BMS (E=598,D=599) PK (n=106)               3yr

ENDEAVOR II CA      Continued Access Single Arm (n=296)              2yr
ENDEAVOR III        3:1 RCT vs. Cypher® (E=323,C=113)                2yr
ENDEAVOR IV         1:1 RCT vs.Taxus® (E=773,T=775)        12mo

ENDEAVOR PK        22,519 Patients 9mo
                    Pharmacokinetic Study (n=43)

ENDEAVOR Japan      Single Arm (n=99)                          9mo

                                Ongoing
                    1:1 RCT vs. Cypher (E=4400,C=4400)
PROTECT
E-FIVE              Open Label Single Arm (n=8000)

                                Proposed
US Post Approval    Open Label Single Arm Study (n=2000)
             Current DES Insights

• Efficacy measures
      The relationship between LL and TLR is non-linear and
       moderate LL may still result in low TLR
      Angiographic follow-up has a profound impact on TLR
• Safety considerations
      DES safety evaluations can no longer be confined to 1
       year, as very late stent thrombosis is increased
       compared with BMS
• Clinical trial design
      Larger non-inferiority RCTs vs. approved DES and even
       larger “real world” studies (both with longer follow-up)
       are now required to discern clinical safety and efficacy
                       Endeavor IV
                   Clinical Trial Design
   Co PIs: Martin B. Leon and David E. Kandzari
                         Single De Novo Native Coronary Lesion
                              Vessel Diameter: 2.5–3.5 mm
                                 Lesion Length: ≤ 27 mm
                                  Pre-dilatation required

                                  1:1 randomization
      Endeavor Stent              N = 1,548 patients              Taxus Stent
          n=774                         80 sites                    n=774
                                          US
Clinical/MACE
                   30d     6mo     8mo      9mo    12mo     2yr   3yr    4yr      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
              Endeavor IV
            Study Endpoints
Primary
• Target vessel failure (TVF) at 9 months
  (pre-specified non-inferiority margin 3.8%)
Secondary
• In-segment late lumen loss at 8 months
  (pre-specified non-inferiority margin 0.2mm)
• Angiographic binary restenosis at 8 months
• Clinical outcomes - TVF, MACE, death, MI, TVR,
  TLR, and stent thrombosis (protocol and ARC
  definitions) at 9, 12, 24, 36, 48, and 60 months
               Endeavor IV
          Key Inclusion Criteria
• Clinical evidence of ischemic coronary disease
• Single de novo lesion in native coronary artery
• Target lesion ≤27mm in length, diameter
  stenosis ≥50% and <100%, and target reference
  vessel diameter ≥2.5mm and ≤3.5mm
• Target vessel TIMI flow ≥2
• Patient able to take dual anti-platelet therapy
  (ASA + thienopyridine) for at least 6 months
                Endeavor IV
            Key Exclusion Criteria
• Acute MI within 72 hours of index procedure
• Previous PCI of target vessel within 9 months pre-
    procedure
•   Planned PCI of any vessel within 30 days post-procedure
•   Hx stroke or TIA within 6 months
•   Active PUD or UGIB within 6 months
•   LVEF <30%
•   Target vessel containing thrombus or with
    excessive tortuosity
• Target lesion in ostial or left main location, >45° bend,
    severe calcification, or involving a bifurcation
           Endeavor IV
       Study Administration
• QCA Core Lab
      Brigham and Women’s Hospital, Boston, MA, USA
      Jeffrey J. Popma, MD

• IVUS Core Lab
      Stanford Interventional Cardiology, CA, USA
      Peter Fitzgerald, MD

• ECG Core Lab
      Harvard Clinical Research Institute, Boston, MA, USA
      Peter Zimetbaum, MD

• Data Coordinating Center
      Harvard Clinical Research Institute, Boston, MA, USA
      Laura Mauri, MD

• Clinical Events Committee/DSMB
      Harvard Clinical Research Institute, Boston, MA, USA
      Donald Cutlip, MD
           Endeavor IV
         Patient Flowchart
                      Patients Enrolled
                          N = 1548



    Endeavor                                     Taxus
                        Randomized
     n = 773                                    n = 775


 Angio F/U (8 mo)                          Angio F/U (8 mo)
     144/164                                   135/164
      87.8%                                     82.3%



    Clinical F/U                              Clinical F/U
 (9 mo)     (12 mo)                        (9 mo)     (12 mo)
758/773     749/773                       749/775    741/775
 98.1%       96.9%                         96.6%       95.6%
                  Endeavor IV - Top Enrollers
                                                  Patients                                                     Patients
C. O’Shaughnessy                                    119      J. Patterson                                        29
Elyria Memorial Hospital, Elyria, OH                         Forsyth Medical Center, Winston-Salem, NC
P. Overlie                                          95       M. Sketch                                           28
Lubbock heart Hospital, Lubbock, TX                          Duke University Medical Center, Durham, NC
B. McLaurin                                         63       M. Leon                                             28
Anderson Medical Center, Anderson, SC                        Columbia Presbyterian Center NY, NY, NY
S. Solomon                                          59       P. Coleman                                          27
Methodist Hospital Houston, Houston, TX                      Sutter Medical Center, Santa Rosa, CA
J. Douglas                                          51       R. Stoler                                           26
Emory Clinic, Atlanta, GA                                    Baylor Heart & Vascular, Dallas, TX
M. Ball                                             51       S. Papadakos                                        26
Heart Center of Indiana, Indianapolis, IN                    New York Hospital of Queens, Flushing, NY
R. Caputo                                           50       J. Singh                                            23
St. Joseph Hospital health Center, Syracuse, NY              Barnes Jewish, St. Louis, MO
A. Jain                                             47       D. Pinto                                            23
Washington Hospital Healthcare, Fremont, CA                  Beth Israel Hospital, Boston, MA
T. Tolleson                                         45       B. Rutherford                                       23
Mother Francis health System, Tyler, TX                      St. Luke’s Hospital, Kansas City, MO
B. Reen                                             44       V. Chilakamarri                                     22
Prsbyterian hospital, Charlotte, NC                          Lutheran Hospital of IN, Fort Wayne, IN
H. Liberman                                         36       R. Prashad                                          22
Emory Crawford Long, Atlanta, GA                             Ocala Regional Medical Center, Ocala, FL
H. Wilson                                           30       T. Bass                                             22
Carolinas Medical Center, Charlotte, NC                      University of Florida, Jacksonville, FL
P. Bajwa                                            29       T. Sacchi                                           20
Nebraska Heart Institute, Lincoln, NE                        NY Methodist/Cornell Heart Center, Brooklyn, NY
                      Endeavor IV
                 Patient Demographics
                           Endeavor        Taxus
                                                       P value
                           (773 pts)     (775 pts)

Age (in years)             63.5  11.1   63.5  11.0   0.930

Men (%)                       66.9          68.5       0.514

Hx Smoking (%)                62.6          60.4       0.401

Family Hx CAD (%)             43.6          42.1       0.603

Diabetes (%)                  31.2          30.5       0.783

Insulin dependant DM (%)      10.3          8.3        0.162

Hypertension (%)              79.4          82.6       0.120

Hyperlipidemia (%)            81.4          84.8       0.078
                        Endeavor IV
                    Clinical CAD History
                           Endeavor       Taxus
                                                      P value
                           (773 pts)    (775 pts)

Prior PCI (%)                28.2          29.5       0.575

Prior MI (%)                 21.1          23.2       0.324

Prior CABG (%)                9.8          8.4        0.332
Angina – Stable (%)          45.6          47.9
         Unstable (%)        51.6          49.9       0.367
         MI (%)              2.8           2.1
CCS III or IV (%)            50.3          47.9       0.392

Positive ETT (%)             88.9          91.1       0.250

CAD – single vessel (%)      54.9          57.2       0.384

LVEF (%)                   57.3  9.9   57.5  10.3   0.745
                  Endeavor IV
          Lesion Characteristics (QCA)
                          Endeavor         Taxus
                                                        P value
                        (773 lesions)   (775 lesions)
Vessel Location (%)                                     0.791
   LAD                      42.2            41.5
   LCX                      26.9            26.1
   RCA                      30.8            32.4
ACC/AHA Lesion class                                    0.358
   A                        6.7             6.6
   B1                       23.7            22.5
   B2                       43.8            42.9
   C                        25.8            28.0
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
                  Endeavor IV
                Post-Procedure QCA
                       Endeavor          Taxus
                                                     P value
                       (770 pts)       (772 pts)

RVD (mm)              2.79  0.47     2.76  0.47    0.237
MLD (mm)
   In-stent           2.62  0.43     2.61  0.44    0.703
   In-segment         2.22  0.47     2.19  0.50    0.196
% DS
   In-stent           5.50  9.61    5.01  10.49    0.348
   In-segment         20.47  9.54   20.97  11.12   0.344
Acute gain (mm)
   In-stent           1.66  0.48     1.68  0.47    0.425
   In-segment         1.26  0.50     1.26  0.51    0.937
                 Endeavor IV
                 8 Month QCA
                    Endeavor           Taxus
                                                   P value
                    (144 pts)        (135 pts)

RVD (mm)            2.65  0.47     2.68  0.45    0.635
MLD (mm)
   In-stent         1.95  0.61     2.25  0.61    <0.001
   In-segment       1.80  0.55     1.98  0.56    0.008
% DS
   In-stent        26.41  19.74   16.09  17.99   <0.001
   In-segment      32.28  17.02   26.61  15.52   0.004
Late loss (mm)
   In-stent         0.67  0.49     0.42  0.50    <0.001
   In-segment       0.36  0.47     0.23  0.45    0.023
                 Endeavor IV
                 8 Month QCA
                    Endeavor           Taxus
                                                   P value
                    (144 pts)        (135 pts)

RVD (mm)            2.65  0.47     2.68  0.45    0.635
MLD (mm)
   In-stent         1.95  0.61     2.25  0.61    <0.001
   In-segment       1.80  0.55     1.98  0.56    0.008
% DS
   In-stent        26.41  19.74   16.09  17.99   <0.001
   In-segment      32.28  17.02   26.61  15.52   0.004
Late loss (mm)
   In-stent         0.67  0.49     0.42  0.50    <0.001
   In-segment       0.36  0.47     0.23  0.45    0.023
            Endeavor IV
     Restenosis at 8 Months (QCA)
                            Endeavor      Taxus
                                                    P value
                            (144 pts)   (135 pts)

Binary Restenosis - % (#)

   In-stent                 13.3 (19)    6.7 (9)    0.075

   Proximal edge             3.6 (5)     3.8 (5)    1.000

   Distal edge               0.7 (1)     0.7 (1)    1.000

   In-segment               15.3 (22)   10.4 (14)   0.284
                        Endeavor IV
            Clinical Events at 30 days
                                     Endeavor      Taxus
                                                             P-Value
                                     (770 pts)   (772 pts)
Death (all) – % (#)                   0.3 (2)       0         0.249
      Cardiac                         0.1 (1)       0         0.499
MI (all) – % (#)                      0.8 (6)    2.3 (18)     0.022
      Q Wave                          0.3 (2)     0.1 (1)     0.624
      Non Q wave                      0.5 (4)    2.2 (17)     0.007
Death (cardiac) + MI (all) – % (#)    0.9 (7)    2.3 (18)     0.042
Stent Thrombosis (all) – % (#)        0.4 (3)     0.1 (1)     0.374
TLR – % (#)                           0.4 (3)     0.8 (6)     0.507
TVR (non-TL) – % (#)                    0         0.3 (2)     0.500
TVR – % (#)                           0.4 (3)     0.9 (7)     0.342
MACE – % (#)                          1.2 (9)    3.0 (23)     0.019
TVF – % (#)                           1.0 (8)    3.0 (23)     0.010
                        Endeavor IV
            Clinical Events at 30 days
                                     Endeavor      Taxus
                                                             P-Value
                                     (770 pts)   (772 pts)
Death (all) – % (#)                   0.3 (2)       0         0.249
      Cardiac                         0.1 (1)       0         0.499
MI (all) – % (#)                      0.8 (6)    2.3 (18)     0.022
      Q Wave                          0.3 (2)     0.1 (1)     0.624
      Non Q wave                      0.5 (4)    2.2 (17)     0.007
Death (cardiac) + MI (all) – % (#)    0.9 (7)    2.3 (18)     0.042
Stent Thrombosis (all) – % (#)        0.4 (3)     0.1 (1)     0.374
TLR – % (#)                           0.4 (3)     0.8 (6)     0.507
TVR (non-TL) – % (#)                    0         0.3 (2)     0.500
TVR – % (#)                           0.4 (3)     0.9 (7)     0.342
MACE – % (#)                          1.2 (9)    3.0 (23)     0.019
TVF – % (#)                           1.0 (8)    3.0 (23)     0.010
                                 Endeavor IV
                  Peri-procedural MIs (CKMB rises)
                          CKMB Rises (xULN)

                         8/17 (47%) of Taxus non-Q MIs        8
                           with CKMB rises 10X ULN
Number Patients




                                                   2
                     1       1             1
                                      0
                     ≥5X<8X          ≥8X<10X           ≥10X
           Endeavor IV
Primary Endpoint Result at 9 months
           Target Vessel Failure
            P for Non-Inferiority < 0.001
                      Δ=3.8%

             6.6%                  7.2%
TVF Rate




           Endeavor                Taxus
           (n=50/758)            (n=54/749)
                Endeavor IV
        Clinical Events at 9 months
                                        Endeavor         Taxus
                                                                    P-Value
                                         n=758           n=749
Death (all) – % (#)                       0.7 (5)        0.8 (6)     0.772
      Cardiac                             0.4 (3)        0.3 (2)     1.000
MI (all) – % (#)                          1.5 (11)       2.4 (18)    0.194
      Q Wave                              0.3 (2)        0.1 (1)     1.000
      Non Q wave                          1.2 (9)        2.3 (17)    0.117
Death (cardiac) + MI (all) – % (#)        1.8 (14)       2.7 (20)    0.303
Stent Thrombosis (all) – % (#)            0.8 (6)        0.1 (1)     0.124
          0-30 days                       0.4 (3)        0.1 (1)     0.625
          31-270days                      0.4* (3)          0        0.250
TLR – % (#)                               4.1 (31)       2.7 (20)    0.154
TVR (non-TL) – % (#)                      2.0 (15)       2.8 (21)    0.316
TVR – % (#)                               5.4 (41)       4.9 (37)    0.728
MACE – % (#)                              5.5 (42)       5.6 (42)    1.000
TVF – % (#)                               6.6 (50)       7.2 (54)    0.685

                                     *Day 83, 145, 171
                Endeavor IV
       Clinical Events at 12 months
                                        Endeavor         Taxus
                                                                    P-Value
                                         n=749           n=741
Death (all) – % (#)                        1.1(8)        1.1(8)      1.000
      Cardiac                             0.5 (4)        0.5 (4)     1.000
MI (all) – % (#)                          1.6 (12)       2.6 (19)    0.208
      Q Wave                              0.3 (2)        0.1 (1)     1.000
      Non Q wave                          1.3 (10)       2.4 (18)    0.131
Death (cardiac) + MI (all) – % (#)        2.1 (16)       3.1 (23)    0.260
Stent Thrombosis (all) – % (#)            0.8 (6)        0.1 (1)     0.124
          0-30 days                       0.4 (3)        0.1 (1)     0.625
          31-360days                      0.4* (3)          0        0.250
TLR – % (#)                               4.5 (34)       3.2 (24)    0.228
TVR (non-TL) – % (#)                      2.5 (19)       4.2 (31)    0.085
TVR – % (#)                               6.3 (47)       6.7 (50)    0.753
MACE – % (#)                              6.5 (49)       6.6 (49)    1.000
TVF – % (#)                               7.7 (58)       9.4 (70)    0.267

                                     *Day 83, 145, 171
              Endeavor IV
          Target Vessel Failure
          9 months               12 months
                                    P = 0.267
             P = 0.685
                                            9.4%
                                7.7%
                     7.2%
        6.6%
Rate




       Endeavor      Taxus     Endeavor     Taxus
        (50/758)    (54/749)    (58/749)   (70/741)
               Endeavor IV
         Death and MI at 9 months
          Endeavor (n=758)
          Taxus (n=749)
                                     P =0.194
                                                                  P =0.117
                                            2.4%
                                                                        2.3%
Rate




                                     1.5%
        P =0.772                                                 1.2%

               0.8%     P =1.000                    P =1.000
        0.7%
                       0.4%
                              0.3%                 0.3%
                                                          0.1%


       Death All      Card Death      MI All       Q-wave         Non-Q
              Endeavor IV
        Death and MI at 12 months
          Endeavor (n=749)
          Taxus (n=741)          P =0.208
                                                              P =0.131
                                        2.6%
                                                                    2.4%



                                 1.6%
Rate




        P =1.000
                                                             1.3%
        1.1% 1.1%
                      P =1.000
                                                P =1.000
                     0.5% 0.5%
                                               0.3%
                                                      0.1%


       Death All    Card Death    MI All       Q-wave         Non-Q
         Endeavor IV
Target Vessel Revascularization
          9 months               12 months

                                     P = 0.753
             P = 0.728

                                6.3%         6.7%
        5.4%
Rate




                     4.9%




       Endeavor      Taxus     Endeavor     Taxus
        (41/758)    (37/749)    (47/749)   (50/741)
         Endeavor IV
Target Lesion Revascularization
          9 months               12 months


                                     P = 0.228
             P = 0.154
Rate




        4.1%                    4.5%
                     2.7%                    3.2%




       Endeavor      Taxus     Endeavor     Taxus
        (31/758)    (20/749)    (34/749)   (24/741)
                                Endeavor IV
Relative Changes in Clinical Endpoints
         from 9 to 12 Months
                                                         Endeavor
                                                         Taxus
 Percent Increase




                                                               50%


                                      37%
                          31%
                                                         25%
                                                  19%
                    17%         17%
                                            10%



                      TVF         TVR         TLR       Non TL-TVR
                  Endeavor IV
           ALL TLR Events at 12 months
                                              Endeavor (n=749)

               P =0.737                       Taxus (n=741)

              5.9%
                      5.4%      P =0.228
TLR Rate




                               4.5%

                                      3.2%      P =0.241

                                                     2.2%
                                              1.3%

               44         40    34     24      10     16

                    All        Clinically    Non-clinically
                                Driven          Driven
                        Endeavor IV
TVR by Angiographic Follow-up at 12 months
                   P =0.389

                9.9%
                                          P =0.401


                              6.8%                   6.7%
 TVR Rate




                                       5.4%




               14/141     9/133       33/608     41/608
             Endeavor     Taxus      Endeavor    Taxus
            Angiographic Follow-up    Clinical Follow-up
                        Endeavor IV
TLR by Angiographic Follow-up at 12 months
                   P =0.070


               8.5%


                                           P =0.875
 TLR Rate




                                       3.6%           3.3%
                              3.0%



               12/141     4/133       22/608      20/608
             Endeavor     Taxus      Endeavor     Taxus
            Angiographic Follow-up    Clinical Follow-up
                                  Endeavor IV
                          TVF Free Survival to 360 days


                                                                 Endeavor            Taxus   P (log rank)
                   100%
                                                          TVF-free     92.3%         90.6%         0.243
Freedom from TVF




                   95%



                   90%
                                   Endeavor          Taxus

                   85%
                          0   30   60   90    120   150    180   210   240     270    300    330     360
                                        Time after Initial Procedure (days)
                                               Endeavor IV
 Cardiac Death/MI Free Survival to 360 days

                     100%                                                Endeavor       Taxus   P (log rank)
                                                            CD/MI-free    97.9%         97.0%         0.253
Freedom from CD/MI




                     99%

                     98%

                     97%

                     96%
                                     Endeavor          Taxus
                     95%
                            0   30   60   90    120   150    180   210     240    270    300    330    360
                                          Time after Initial Procedure (days)
                                  Endeavor IV
                          TVR Free Survival to 360 days

                                                                       Endeavor       Taxus    P (log rank)
                   100%                                   TVR-free      93.7%         93.3%         0.727
Freedom from TVR




                   95%



                                   Endeavor          Taxus

                   90%
                          0   30   60   90    120   150    180   210    240     270    300    330    360
                                        Time after Initial Procedure (days)
                                  Endeavor IV
                          TLR Free Survival to 360 days
                                                                       Endeavor       Taxus    P (log rank)
                   100%                                   TLR-free      95.5%         96.8%         0.195
Freedom from TLR




                   95%



                                   Endeavor          Taxus

                   90%
                          0   30   60   90    120   150    180   210    240     270    300    330    360
                                        Time after Initial Procedure (days)
       Endeavor IV - Diabetics
         TVF and TLR at 12 months
            P =0.526


                      10.8%        P =0.704

         8.6%

                                6.9%
                                              5.8%
Rate




        20/233     24/223      16/233     13/223
       Endeavor       Taxus   Endeavor    Taxus

                TVF                     TLR
        477 diabetics (30.8% of E IV patients)
                                       Endeavor IV
       TVF (9M) – Post Hoc Subgroup Analysis
                              Risk Ratio                                                         P-Value
                                                         Risk Ratio   Endeavor      Taxus
                               [95% CI]                                                        Interaction

Diabetes                                                 0.91         7.7% (18)   8.4% (19)       0.989

Non-diabetes                                             0.91         6.1% (32)   6.7% (35)

RVD
  2.5mm                                                 0.81         7.1% (18)   8.8% (23)       0.759
   >2.5 <3.0mm                                           1.13         7.0% (21)   6.2% (18)
  3.0mm                                                 0.81         5.4% (11)   6.6% (13)

Lesion Length
  10mm                                                  0.65         4.3% (10)   6.6% (15)       0.430
   >10 <20mm                                             1.19         7.9% (34)   6.6% (27)
  20mm                                                  0.50         5.5% (5)    10.9% (12)


Single Stent                                             1.01         6.1% (43)   6.1% (40)       0.873
Multiple Stents                                          0.93         13.6% (6)   14.7% (11)

                  0.1    Favors    1       Favors   10
                        Endeavor           Taxus
                                       Endeavor IV
Cardiac Death/MI (9M) – Post Hoc Subgroup Analysis
                              Risk Ratio                                                        P-Value
                                                         Risk Ratio   Endeavor     Taxus
                               [95% CI]                                                       Interaction

Diabetes                                                 0.64         0.9% (2)    1.3% (3)       0.927

Non-diabetes                                             0.71         2.3% (12)   3.3% (17)

RVD
  2.5mm                                                 0.23         0.8% (2)    3.4% (9)       0.429
   >2.5 <3.0mm                                           1.55         2.7% (8)    1.7% (5)
  3.0mm                                                 0.64         2.0% (4)    3.1% (6)

Lesion Length
  10mm                                                  0.16         0.4% (1)    2.6% (6)       0.849
   >10 <20mm                                             1.42         2.8% (12)   2.0% (8)
  20mm                                                  0.20         1.1% (1)    5.5% (6)


Single Stent                                             0.70         1.7% (12)   2.4% (16)      0.844
Multiple Stents                                          0.85         4.5% (2)    5.3% (4)

                  0.1    Favors    1       Favors   10
                        Endeavor           Taxus
                                       Endeavor IV
       TVR (9M) – Post Hoc Subgroup Analysis
                              Risk Ratio                                                        P-Value
                                                         Risk Ratio   Endeavor     Taxus
                               [95% CI]                                                       Interaction

Diabetes                                                 1.02         7.7% (18)   7.5% (17)      0.789

Non-diabetes                                             1.15         4.4% (23)   3.8% (20)

RVD
  2.5mm                                                 1.10         6.7% (17)   6.1% (16)      0.791
   >2.5 <3.0mm                                           1.04         4.7% (14)   4.5% (13)
  3.0mm                                                 1.20         4.9% (10)   4.1% (8)

Lesion Length
  10mm                                                  0.97         4.3% (10)   4.4% (10)      0.415
   >10 <20mm                                             1.17         6.0% (26)   5.1% (21)
  20mm                                                  0.81         4.4% (4)    5.5% (6)


Single Stent                                             1.30         5.1% (36)   3.9% (26)      0.516
Multiple Stents                                          0.85         9.1% (4)    10.7% (8)

                  0.1    Favors    1       Favors   10
                        Endeavor           Taxus
                                       Endeavor IV
       TLR (9M) – Post Hoc Subgroup Analysis
                              Risk Ratio                                                        P-Value
                                                         Risk Ratio   Endeavor     Taxus
                               [95% CI]                                                       Interaction

Diabetes                                                 1.04         6.0% (14)   5.8% (13)      0.149

Non-diabetes                                             2.43         3.3% (17)   1.3% (7)

RVD
  2.5mm                                                 1.13         4.3% (11)   3.8% (10)      0.514
   >2.5 <3.0mm                                           1.66         4.0% (12)   2.4% (7)
  3.0mm                                                 2.56         3.9% (8)    1.5% (3)

Lesion Length
  10mm                                                  1.36         3.0% (7)    2.2% (5)       .0481
   >10 <20mm                                             1.64         4.4% (19)   2.7% (11)
  20mm                                                  1.21         4.4% (4)    3.6% (4)


Single Stent                                             2.03         3.7% (26)   1.8% (12)      0.616
Multiple Stents                                          1.36         9.1% (4)    6.7% (5)

                  0.1    Favors    1       Favors   10
                        Endeavor           Taxus
        Endeavor IV at 12 months
           Multivariate TLR Predictors
                 for All patients

Multiple Logistic
                         Odds Ratio        P-Value
Regression
Diabetes              2.79 [1.604,4.867]    <.001
Multiple vs. Single
                      3.11 [1.502,6.443]    0.002
stents
LAD vs. Non LAD       1.83 [1.055,3.186]    0.032


Taxus vs. Endeavor    1.42 [0.834,2.420]    0.196
         Endeavor IV at 12 months
           Multivariate TLR Predictors
            for Endeavor and Taxus

Endeavor
                              Odds Ratio          P-Value
MV TLR Predictors

Angiography FU               2.49 [1.196,5.136]    0.015

Taxus
                               Odds Ratio         P-Value
MV TLR Predictors

Diabetes                     3.76 [1.518,9.318]     0.004

Multiple vs. Single stents   3.11 [1.502,6.443]     0.005
Age                          1.06 [1.012,1.110]     0.013
                 Endeavor IV
                 Conclusions
The Endeavor DES, compared with the
Taxus DES, demonstrated…
• Reduced peri-procedural non-Q MIs, and a similar
  overall safety profile (death, Q-MI, and stent
  thrombosis) through 12 months follow-up
• Higher angiographic late loss at 8 months follow-up
• Similar TVF (1ry endpoint) through 12 months
  follow-up
• Similar TVR/TLR in subsets of interest (including
  diabetics) through 12 months follow-up, especially
  in the clinical FU patient cohort

				
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