Endeavor IV: A Randomized Comparison of a Zotarolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Corona...
Presenter Disclosure Information for TCT 2007; October 20-25, 2007 Martin B. Leon, M.D. Scientific Advisory Board:   Medtr...
Endeavor DES System PC Technology Drug: Zotarolimus Stent Delivery System Driver Cobalt Alloy Stent
Polymer and Drug Matrix Tissue Blood PC Basecoat  (≈ 1μm thick) Drug Layer 90% Zotarolimus (10 μ g/mm) 10% PC   (≈ 2-4μm t...
Porcine Drug Elution Kinetics and PK <ul><li>Zotarolimus is hydrophobic and rapidly elutes from  the hydrophilic PC polyme...
Biocompatibility (Inflammation Scores) <ul><li>Porcine inflammation scores show mild response to a  3X overdose (30μg/mm) ...
Endothelial Coverage <ul><li>Porcine histology and SEM show rapid endothelial replacement with both single and overlapping...
Preserved Endothelial Function In Vivo Assessment of Endothelial Function in Porcine Models: eNOS Staining Endeavor Driver...
Preserved Endothelial Function  In Vivo Assessment of Endothelial Function Porcine Model: Active Vasoreactivity Driver End...
Endeavor Clinical Program Overview   9m  2yr  3yr  4yr ENDEAVOR I ENDEAVOR II ENDEAVOR II CA ENDEAVOR III ENDEAVOR IV ENDE...
Endeavor Clinical Program Overview   9m  2yr  3yr  4yr ENDEAVOR I ENDEAVOR II ENDEAVOR II CA ENDEAVOR III ENDEAVOR IV ENDE...
Current DES Insights  <ul><li>Efficacy measures </li></ul><ul><ul><li>The relationship between LL and TLR is non-linear an...
Endeavor IV Clinical Trial Design     Co PIs: Martin B. Leon and David E. Kandzari Primary Endpoint: TVF at 9 months Secon...
Endeavor IV Study Endpoints <ul><li>Primary </li></ul><ul><li>Target vessel failure (TVF) at 9 months  (pre-specified non-...
Endeavor IV Key Inclusion Criteria <ul><li>Clinical evidence of ischemic coronary disease </li></ul><ul><li>Single  de nov...
Endeavor IV Key Exclusion Criteria <ul><li>Acute MI within 72 hours of index procedure </li></ul><ul><li>Previous PCI of t...
Endeavor IV Study Administration <ul><li>QCA Core Lab </li></ul><ul><ul><li>Brigham and Women’s Hospital, Boston, MA, USA ...
Endeavor IV Patient Flowchart   Angio F/U (8 mo) 135/164 82.3% Patients Enrolled N = 1548 Randomized Endeavor n = 773 Taxu...
Endeavor IV -  Top Enrollers Patients Patients 20 T. Sacchi NY Methodist/Cornell Heart Center, Brooklyn, NY 29 P. Bajwa Ne...
Endeavor IV   Patient Demographics 0.078 84.8 81.4 Hyperlipidemia (%) 0.120 82.6 79.4 Hypertension (%) 0.930 63.5    11.0...
Endeavor IV   Clinical CAD History 0.745 57.5    10.3 57.3    9.9 LVEF (%) 0.384 57.2 54.9 CAD – single vessel (%) 0.575...
Endeavor IV   Lesion Characteristics (QCA) 0.199 13.80    6.09 13.41    5.67 Lesion length (mm) 0.204 65.68    13.10 64...
Endeavor IV   Post-Procedure QCA 0.937 1.26    0.51 1.26    0.50 In-segment 0.425 1.68    0.47 1.66    0.48 In-stent A...
Endeavor IV   8 Month QCA 0.023 0.23    0.45 0.36    0.47 In-segment <0.001 0.42    0.50 0.67    0.49 In-stent Late lo...
Endeavor IV   8 Month QCA 0.023 0.23    0.45 0.36    0.47 In-segment <0.001 0.42    0.50 0.67    0.49 In-stent Late lo...
Endeavor IV   Restenosis at 8 Months (QCA) 0.284 10.4 (14) 15.3 (22) In-segment Binary Restenosis - % (#) 0.7 (1) 3.8 (5) ...
Endeavor IV Clinical Events at 30 days 0.500 0.3 (2) 0  TVR (non-TL) – % (#) 0.042 2.3 (18) 0.9 (7) Death (cardiac) + MI (...
Endeavor IV Clinical Events at 30 days 0.500 0.3 (2) 0  TVR (non-TL) – % (#) 0.042 2.3 (18) 0.9 (7) Death (cardiac) + MI (...
Endeavor IV    Peri-procedural MIs (CKMB rises) CKMB Rises (xULN) 8/17 (47%) of Taxus non-Q MIs  with CKMB rises   10X UL...
Endeavor IV    Primary Endpoint Result at 9 months Target Vessel Failure TVF Rate P for Non-Inferiority < 0.001 Δ =3.8% Ta...
Endeavor IV Clinical Events at 9 months *Day 83, 145, 171 0.316 2.8 (21) 2.0 (15) TVR (non-TL) – % (#) 0.625 0.1 (1) 0.4 (...
Endeavor IV Clinical Events at 12 months *Day 83, 145, 171 0.085 4.2 (31) 2.5 (19) TVR (non-TL) – % (#) 0.625 0.1 (1) 0.4 ...
Endeavor IV   Target Vessel Failure   Endeavor (50/758) Taxus (54/749) Endeavor (58/749) Taxus (70/741) P  = 0.685 9 month...
Endeavor IV   Death and MI at 9 months  Card Death  Non-Q Rate 0.7% 0.8% P  =0.772 P  =1.000 P  =1.000 P  =0.117 0.3% 0.4%...
Endeavor IV   Death and MI at 12 months  Card Death  Non-Q Rate 1.1% 1.1% P  =1.000 P  =1.000 P  =1.000 P  =0.131 0.5% 0.5...
Endeavor IV   Target Vessel Revascularization   Endeavor (41/758) Taxus (37/749) Endeavor (47/749) Taxus (50/741) P  = 0.7...
Endeavor IV   Target Lesion Revascularization   Endeavor (31/758) Taxus (20/749) Endeavor (34/749) Taxus (24/741) P  = 0.1...
Endeavor IV   Relative Changes in Clinical Endpoints  from 9 to 12 Months   TVR Percent Increase 17% 31% 37% 17% 10% 19% 2...
Endeavor IV   ALL TLR Events at 12 months   All Clinically  Driven Non-clinically  Driven TLR Rate 44 40 34 24 10 16 P  =0...
Endeavor IV    TVR by Angiographic Follow-up at 12 months TVR Rate 14/141 9/133 33/608 41/608 Endeavor Taxus Endeavor Taxu...
Endeavor IV    TLR by Angiographic Follow-up at 12 months TLR Rate 12/141 4/133 22/608 20/608 Endeavor Taxus Endeavor Taxu...
Endeavor IV TVF Free Survival to 360 days Freedom from TVF 100% 85% 0 30 60 90 120 150 180 210 240 270 300 330 360 Time af...
Endeavor IV Cardiac Death/MI Free Survival to 360 days Freedom from CD/MI 100% 95% 97% 98% Time after Initial Procedure (d...
Endeavor IV TVR Free Survival to 360 days Freedom from TVR 100% 90% 95% 0 30 60 90 120 150 180 210 240 270 300 330 360 Tim...
Endeavor IV TLR Free Survival to 360 days Freedom from TLR 100% 90% 95% 0 30 60 90 120 150 180 210 240 270 300 330 360 Tim...
Endeavor IV - Diabetics    TVF and TLR at 12 months Rate 20/233 24/223 16/233 13/223 Endeavor Taxus Endeavor Taxus P  =0.5...
Endeavor IV  TVF (9M) – Post Hoc Subgroup Analysis   Diabetes Non-diabetes RVD  2.5mm   >2.5 <3.0mm  3.0mm Lesion Length...
Endeavor IV  Cardiac Death/MI (9M) – Post Hoc Subgroup Analysis   Diabetes Non-diabetes RVD  2.5mm   >2.5 <3.0mm  3.0mm ...
Endeavor IV  TVR (9M) – Post Hoc Subgroup Analysis   Diabetes Non-diabetes RVD  2.5mm   >2.5 <3.0mm  3.0mm Lesion Length...
Endeavor IV  TLR (9M) – Post Hoc Subgroup Analysis   Diabetes Non-diabetes RVD  2.5mm   >2.5 <3.0mm  3.0mm Lesion Length...
Endeavor IV at 12 months Multivariate TLR Predictors for All patients P-Value Odds Ratio Multiple Logistic Regression 0.00...
Endeavor IV at 12 months Multivariate TLR Predictors for Endeavor and Taxus P-Value Odds Ratio Endeavor MV TLR Predictors ...
Endeavor IV Conclusions <ul><li>Reduced peri-procedural non-Q MIs, and a similar  overall safety profile (death, Q-MI, and...
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Endeavor IV-A Randomized Comparison of a Zotarolimus-Eluting Stent Endeavor IV-A Randomized Comparison of a Zotarolimus-Eluting Stent

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  • Endeavor IV-A Randomized Comparison of a Zotarolimus-Eluting Stent Endeavor IV-A Randomized Comparison of a Zotarolimus-Eluting Stent

    1. 1. 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
    2. 2. 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
    3. 3. Endeavor DES System PC Technology Drug: Zotarolimus Stent Delivery System Driver Cobalt Alloy Stent
    4. 4. Polymer and Drug Matrix Tissue Blood PC Basecoat (≈ 1μm thick) Drug Layer 90% Zotarolimus (10 μ g/mm) 10% PC (≈ 2-4μm thick) PC Overspray (≈ 0.1 μm thick) Stent Strut 3.0 mm Stents 500x magnification Illustrative Not to Scale Taxus Cypher Endeavor
    5. 5. Porcine Drug Elution Kinetics and PK <ul><li>Zotarolimus is hydrophobic and rapidly elutes from the hydrophilic PC polymer matrix within 14 days </li></ul>Blood and Arterial Tissue Zotarolimus Concentration <ul><li>Zotarolimus is highly lipophilic enabling rapid arterial tissue loading and drug retention which is sustained for ~28 days </li></ul>Drug Elution by Recovered Drug from Stent Concentration (Blood) ng/ml Days Concentration (Tissue) ng/ml Blood Tissue % Drug Eluted Time (Days) 65 87 98 99
    6. 6. Biocompatibility (Inflammation Scores) <ul><li>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. </li></ul>*CVPath, Dr Renu Virmani Inflammation Scores Inflammation Scores 1 28 to 180 days Inflammation Scores 1 28 to 180 days Inflammation Scores Days Days 1 Bare stent controls matched with test groups 2 Not Done *P<0.05 compared to the respective controls 1 Bare stent controls matched with test groups 2 Not Done *P<0.05 compared to the respective controls 4 9 4 5 8 n 7 28 90 180 7 6 4 5 7 n 7 28 90 180 9 7 ND 2 * * ND 2 * *
    7. 7. Endothelial Coverage <ul><li>Porcine histology and SEM show rapid endothelial replacement with both single and overlapping (OL) stents*. </li></ul>1 Bare stent controls matched with test groups 1 Bare stent controls matched with test groups *P<0.05 compared to respective controls % Endotheliazation Percent Endothelialization 1 7 to 180 days Days Days 7 28 90 180 7 28 90 180 Single Stents Overlapping (OL) Stents % Endotheliazation * Study Number FS102 FS99 FS100 FS11 Study Number FS102 FS99 FS100 FS11 Percent Endothelialization 1 7 to 180 days *CVPath, Dr Renu Virmani
    8. 8. Preserved Endothelial Function In Vivo Assessment of Endothelial Function in Porcine Models: eNOS Staining Endeavor Driver Immunohistochemistry Staining for Presence of eNOS
    9. 9. Preserved Endothelial Function In Vivo Assessment of Endothelial Function Porcine Model: Active Vasoreactivity Driver Endeavor Distal Vessel Vasoreactivity Following Acetylcholine (Ach) Challenge Baseline Ach (10 -5M ) mm 90d 28d Baseline Ach (10 -5M ) mm Baseline Ach (10 -5M ) mm 90d Baseline Ach (10 -5M ) mm 28d
    10. 10. Endeavor Clinical Program Overview 9m 2yr 3yr 4yr ENDEAVOR I ENDEAVOR II ENDEAVOR II CA ENDEAVOR III ENDEAVOR IV ENDEAVOR PK Single Arm First-in-Man (n=100) 4yr 1:1 RCT vs. BMS (E=598,D=599) PK (n=106) 3yr Continued Access Single Arm (n=296) 2yr 3:1 RCT vs . Cypher ® (E=323,C=113) 2yr 1:1 RCT vs.Taxus ® (E=773,T=775) 12mo Pharmacokinetic Study (n=43) 9mo Single Arm (n=99) 9mo ENDEAVOR Japan E-FIVE Open Label Single Arm (n=8000) US Post Approval PROTECT 1:1 RCT vs. Cypher (E=4400,C=4400) Open Label Single Arm Study (n=2000) Proposed Ongoing Premarket Safety and Efficacy Package
    11. 11. Endeavor Clinical Program Overview 9m 2yr 3yr 4yr ENDEAVOR I ENDEAVOR II ENDEAVOR II CA ENDEAVOR III ENDEAVOR IV ENDEAVOR PK Single Arm First-in-Man (n=100) 4yr 1:1 RCT vs. BMS (E=598,D=599) PK (n=106) 3yr Continued Access Single Arm (n=296) 2yr 3:1 RCT vs . Cypher ® (E=323,C=113) 2yr 1:1 RCT vs.Taxus ® (E=773,T=775) 12mo Pharmacokinetic Study (n=43) 9mo Single Arm (n=99) 9mo ENDEAVOR Japan E-FIVE Open Label Single Arm (n=8000) US Post Approval PROTECT 1:1 RCT vs. Cypher (E=4400,C=4400) Open Label Single Arm Study (n=2000) Proposed Ongoing Premarket Safety and Efficacy Package 22,519 Patients
    12. 12. Current DES Insights <ul><li>Efficacy measures </li></ul><ul><ul><li>The relationship between LL and TLR is non-linear and moderate LL may still result in low TLR </li></ul></ul><ul><ul><li>Angiographic follow-up has a profound impact on TLR </li></ul></ul><ul><li>Safety considerations </li></ul><ul><ul><li>DES safety evaluations can no longer be confined to 1 year, as very late stent thrombosis is increased compared with BMS </li></ul></ul><ul><li>Clinical trial design </li></ul><ul><ul><li>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 </li></ul></ul>
    13. 13. Endeavor IV Clinical Trial Design Co PIs: Martin B. Leon and David E. Kandzari 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 Single De Novo Native Coronary Lesion Vessel Diameter: 2.5–3.5 mm Lesion Length: ≤ 27 mm Pre-dilatation required 1:1 randomization N = 1,548 patients 80 sites US Endeavor Stent n=774 Taxus Stent n=774 30d 6mo 4yr 3yr 2yr 9mo 12mo 8mo 5yr Clinical/MACE Angiography/IVUS QCA and IVUS Subset (328 total = 21.2%)
    14. 14. Endeavor IV Study Endpoints <ul><li>Primary </li></ul><ul><li>Target vessel failure (TVF) at 9 months (pre-specified non-inferiority margin 3.8%) </li></ul><ul><li>Secondary </li></ul><ul><li>In-segment late lumen loss at 8 months (pre-specified non-inferiority margin 0.2mm) </li></ul><ul><li>Angiographic binary restenosis at 8 months </li></ul><ul><li>Clinical outcomes - TVF, MACE, death, MI, TVR, TLR, and stent thrombosis (protocol and ARC definitions) at 9, 12, 24, 36, 48, and 60 months </li></ul>
    15. 15. Endeavor IV Key Inclusion Criteria <ul><li>Clinical evidence of ischemic coronary disease </li></ul><ul><li>Single de novo lesion in native coronary artery </li></ul><ul><li>Target lesion ≤ 27mm in length, diameter stenosis ≥ 50% and <100%, and target reference vessel diameter ≥ 2.5mm and ≤ 3.5mm </li></ul><ul><li>Target vessel TIMI flow ≥ 2 </li></ul><ul><li>Patient able to take dual anti-platelet therapy (ASA + thienopyridine) for at least 6 months </li></ul>
    16. 16. Endeavor IV Key Exclusion Criteria <ul><li>Acute MI within 72 hours of index procedure </li></ul><ul><li>Previous PCI of target vessel within 9 months pre-procedure </li></ul><ul><li>Planned PCI of any vessel within 30 days post-procedure </li></ul><ul><li>Hx stroke or TIA within 6 months </li></ul><ul><li>Active PUD or UGIB within 6 months </li></ul><ul><li>LVEF <30% </li></ul><ul><li>Target vessel containing thrombus or with excessive tortuosity </li></ul><ul><li>Target lesion in ostial or left main location, >45 ° bend, severe calcification, or involving a bifurcation </li></ul>
    17. 17. Endeavor IV Study Administration <ul><li>QCA Core Lab </li></ul><ul><ul><li>Brigham and Women’s Hospital, Boston, MA, USA </li></ul></ul><ul><ul><li>Jeffrey J. Popma, MD </li></ul></ul><ul><li>IVUS Core Lab </li></ul><ul><ul><li>Stanford Interventional Cardiology, CA, USA </li></ul></ul><ul><ul><li>Peter Fitzgerald, MD </li></ul></ul><ul><li>ECG Core Lab </li></ul><ul><ul><li>Harvard Clinical Research Institute, Boston, MA, USA </li></ul></ul><ul><ul><li>Peter Zimetbaum, MD </li></ul></ul><ul><li>Data Coordinating Center </li></ul><ul><ul><li>Harvard Clinical Research Institute, Boston, MA, USA </li></ul></ul><ul><ul><li>Laura Mauri, MD </li></ul></ul><ul><li>Clinical Events Committee/DSMB </li></ul><ul><ul><li>Harvard Clinical Research Institute, Boston, MA, USA </li></ul></ul><ul><ul><li>Donald Cutlip, MD </li></ul></ul>
    18. 18. Endeavor IV Patient Flowchart Angio F/U (8 mo) 135/164 82.3% Patients Enrolled N = 1548 Randomized Endeavor n = 773 Taxus n = 775 Angio F/U (8 mo) 144/164 87.8% Clinical F/U (9 mo) 758/773 98.1% Clinical F/U (9 mo) 749/775 96.6% (12 mo) 749/773 96.9% (12 mo) 741/775 95.6%
    19. 19. Endeavor IV - Top Enrollers Patients Patients 20 T. Sacchi NY Methodist/Cornell Heart Center, Brooklyn, NY 29 P. Bajwa Nebraska Heart Institute, Lincoln, NE 22 T. Bass University of Florida, Jacksonville, FL 30 H. Wilson Carolinas Medical Center, Charlotte, NC 22 R. Prashad Ocala Regional Medical Center, Ocala, FL 36 H. Liberman Emory Crawford Long, Atlanta, GA 22 V. Chilakamarri Lutheran Hospital of IN, Fort Wayne, IN 44 B. Reen Prsbyterian hospital, Charlotte, NC 23 B. Rutherford St. Luke’s Hospital, Kansas City, MO 45 T. Tolleson Mother Francis health System, Tyler, TX 23 D. Pinto Beth Israel Hospital, Boston, MA 47 A. Jain Washington Hospital Healthcare, Fremont, CA 23 J. Singh Barnes Jewish, St. Louis, MO 50 R. Caputo St. Joseph Hospital health Center, Syracuse, NY 26 S. Papadakos New York Hospital of Queens, Flushing, NY 51 M. Ball Heart Center of Indiana, Indianapolis, IN 26 R. Stoler Baylor Heart & Vascular, Dallas, TX 51 J. Douglas Emory Clinic, Atlanta, GA 27 P. Coleman Sutter Medical Center, Santa Rosa, CA 59 S. Solomon Methodist Hospital Houston, Houston, TX 28 M. Leon Columbia Presbyterian Center NY, NY, NY 63 B. McLaurin Anderson Medical Center, Anderson, SC 28 M. Sketch Duke University Medical Center, Durham, NC 95 P. Overlie Lubbock heart Hospital, Lubbock, TX 29 J. Patterson Forsyth Medical Center, Winston-Salem, NC 119 C. O’Shaughnessy Elyria Memorial Hospital, Elyria, OH
    20. 20. Endeavor IV Patient Demographics 0.078 84.8 81.4 Hyperlipidemia (%) 0.120 82.6 79.4 Hypertension (%) 0.930 63.5  11.0 63.5  11.1 Age (in years) 8.3 30.5 42.1 60.4 68.5 Taxus (775 pts) 0.401 62.6 Hx Smoking (%) 0.162 10.3 Insulin dependant DM (%) 0.783 31.2 Diabetes (%) 43.6 66.9 Endeavor (773 pts) 0.603 0.514 P value Family Hx CAD (%) Men (%)
    21. 21. Endeavor IV Clinical CAD History 0.745 57.5  10.3 57.3  9.9 LVEF (%) 0.384 57.2 54.9 CAD – single vessel (%) 0.575 29.5 28.2 Prior PCI (%) 91.1 47.9 47.9 49.9 2.1 8.4 23.2 Taxus (775 pts) 0.332 9.8 Prior CABG (%) 0.250 88.9 Positive ETT (%) 0.392 50.3 CCS III or IV (%) 45.6 51.6 2.8 21.1 Endeavor (773 pts) 0.367 0.324 P value Angina – Stable (%) Unstable (%) MI (%) Prior MI (%)
    22. 22. Endeavor IV Lesion Characteristics (QCA) 0.199 13.80  6.09 13.41  5.67 Lesion length (mm) 0.204 65.68  13.10 64.83  13.29 % DS 0.149 0.93  0.40 0.96  0.40 MLD (mm) 0.197 2.70  0.46 2.73  0.47 RVD (mm) QCA 28.0 25.8 C 42.9 43.8 B 2 22.5 23.7 B 1 0.791 Vessel Location (%) 6.6 32.4 26.1 41.5 Taxus (775 lesions) 26.9 LCX 6.7 A 0.358 ACC/AHA Lesion class 30.8 42.2 Endeavor (773 lesions) P value RCA LAD
    23. 23. Endeavor IV Post-Procedure QCA 0.937 1.26  0.51 1.26  0.50 In-segment 0.425 1.68  0.47 1.66  0.48 In-stent Acute gain (mm) 0.344 20.97  11.12 20.47  9.54 In-segment 0.348 5.01  10.49 5.50  9.61 In-stent MLD (mm) 0.237 2.76  0.47 2.79  0.47 RVD (mm) 2.19  0.50 2.61  0.44 Taxus (772 pts) 0.196 2.22  0.47 In-segment % DS 2.62  0.43 Endeavor (770 pts) 0.703 P value In-stent
    24. 24. Endeavor IV 8 Month QCA 0.023 0.23  0.45 0.36  0.47 In-segment <0.001 0.42  0.50 0.67  0.49 In-stent Late loss (mm) 0.004 26.61  15.52 32.28  17.02 In-segment <0.001 16.09  17.99 26.41  19.74 In-stent MLD (mm) 0.635 2.68  0.45 2.65  0.47 RVD (mm) 1.98  0.56 2.25  0.61 Taxus (135 pts) 0.008 1.80  0.55 In-segment % DS 1.95  0.61 Endeavor (144 pts) <0.001 P value In-stent
    25. 25. Endeavor IV 8 Month QCA 0.023 0.23  0.45 0.36  0.47 In-segment <0.001 0.42  0.50 0.67  0.49 In-stent Late loss (mm) 0.004 26.61  15.52 32.28  17.02 In-segment <0.001 16.09  17.99 26.41  19.74 In-stent MLD (mm) 0.635 2.68  0.45 2.65  0.47 RVD (mm) 1.98  0.56 2.25  0.61 Taxus (135 pts) 0.008 1.80  0.55 In-segment % DS 1.95  0.61 Endeavor (144 pts) <0.001 P value In-stent
    26. 26. Endeavor IV Restenosis at 8 Months (QCA) 0.284 10.4 (14) 15.3 (22) In-segment Binary Restenosis - % (#) 0.7 (1) 3.8 (5) 6.7 (9) Taxus (135 pts) 1.000 3.6 (5) Proximal edge 1.000 0.7 (1) Distal edge 13.3 (19) Endeavor (144 pts) 0.075 P value In-stent
    27. 27. Endeavor IV Clinical Events at 30 days 0.500 0.3 (2) 0 TVR (non-TL) – % (#) 0.042 2.3 (18) 0.9 (7) Death (cardiac) + MI (all) – % (#) 0.499 0 0.1 (1) Cardiac 0.374 0.1 (1) 0.4 (3) Stent Thrombosis (all) – % (#) 0.624 0.1 (1) 0.3 (2) Q Wave 0.507 0.8 (6) 0.4 (3) TLR – % (#) 0.007 2.2 (17) 0.5 (4) Non Q wave 0.342 0.9 (7) 0.4 (3) TVR – % (#) 0.019 3.0 (23) 1.2 (9) MACE – % (#) 0.022 2.3 (18) 0.8 (6) MI (all) – % (#) 1.0 (8) 0.3 (2) Endeavor (770 pts) 3.0 (23) 0 Taxus (772 pts) 0.010 0.249 P-Value TVF – % (#) Death (all) – % (#)
    28. 28. Endeavor IV Clinical Events at 30 days 0.500 0.3 (2) 0 TVR (non-TL) – % (#) 0.042 2.3 (18) 0.9 (7) Death (cardiac) + MI (all) – % (#) 0.499 0 0.1 (1) Cardiac 0.374 0.1 (1) 0.4 (3) Stent Thrombosis (all) – % (#) 0.624 0.1 (1) 0.3 (2) Q Wave 0.507 0.8 (6) 0.4 (3) TLR – % (#) 0.007 2.2 (17) 0.5 (4) Non Q wave 0.342 0.9 (7) 0.4 (3) TVR – % (#) 0.019 3.0 (23) 1.2 (9) MACE – % (#) 0.022 2.3 (18) 0.8 (6) MI (all) – % (#) 1.0 (8) 0.3 (2) Endeavor (770 pts) 3.0 (23) 0 Taxus (772 pts) 0.010 0.249 P-Value TVF – % (#) Death (all) – % (#)
    29. 29. Endeavor IV Peri-procedural MIs (CKMB rises) CKMB Rises (xULN) 8/17 (47%) of Taxus non-Q MIs with CKMB rises  10X ULN ≥ 5X<8X ≥ 8X<10X ≥ 10X 1 1 0 1 2 8 Number Patients
    30. 30. Endeavor IV Primary Endpoint Result at 9 months Target Vessel Failure TVF Rate P for Non-Inferiority < 0.001 Δ =3.8% Taxus (n=54/749) Endeavor (n=50/758) 7.2% 6.6%
    31. 31. Endeavor IV Clinical Events at 9 months *Day 83, 145, 171 0.316 2.8 (21) 2.0 (15) TVR (non-TL) – % (#) 0.625 0.1 (1) 0.4 (3) 0-30 days 0.250 0 0.4* (3) 31-270days 0.303 2.7 (20) 1.8 (14) Death (cardiac) + MI (all) – % (#) 1.000 0.3 (2) 0.4 (3) Cardiac 0.124 0.1 (1) 0.8 (6) Stent Thrombosis (all) – % (#) 1.000 0.1 (1) 0.3 (2) Q Wave 0.154 2.7 (20) 4.1 (31) TLR – % (#) 0.117 2.3 (17) 1.2 (9) Non Q wave 0.728 4.9 (37) 5.4 (41) TVR – % (#) 1.000 5.6 (42) 5.5 (42) MACE – % (#) 0.194 2.4 (18) 1.5 (11) MI (all) – % (#) 6.6 (50) 0.7 (5) Endeavor n=758 7.2 (54) 0.8 (6) Taxus n=749 0.685 0.772 P-Value TVF – % (#) Death (all) – % (#)
    32. 32. Endeavor IV Clinical Events at 12 months *Day 83, 145, 171 0.085 4.2 (31) 2.5 (19) TVR (non-TL) – % (#) 0.625 0.1 (1) 0.4 (3) 0-30 days 0.250 0 0.4* (3) 31-360days 0.260 3.1 (23) 2.1 (16) Death (cardiac) + MI (all) – % (#) 1.000 0.5 (4) 0.5 (4) Cardiac 0.124 0.1 (1) 0.8 (6) Stent Thrombosis (all) – % (#) 1.000 0.1 (1) 0.3 (2) Q Wave 0.228 3.2 (24) 4.5 (34) TLR – % (#) 0.131 2.4 (18) 1.3 (10) Non Q wave 0.753 6.7 (50) 6.3 (47) TVR – % (#) 1.000 6.6 (49) 6.5 (49) MACE – % (#) 0.208 2.6 (19) 1.6 (12) MI (all) – % (#) 7.7 (58) 1.1(8) Endeavor n=749 9.4 (70) 1.1(8) Taxus n=741 0.267 1.000 P-Value TVF – % (#) Death (all) – % (#)
    33. 33. Endeavor IV Target Vessel Failure Endeavor (50/758) Taxus (54/749) Endeavor (58/749) Taxus (70/741) P = 0.685 9 months 12 months Rate P = 0.267 6.6% 7.2% 7.7% 9.4%
    34. 34. Endeavor IV Death and MI at 9 months Card Death Non-Q Rate 0.7% 0.8% P =0.772 P =1.000 P =1.000 P =0.117 0.3% 0.4% 2.4% 1.5% P =0.194 0.3% 0.1% 1.2% 2.3% Death All MI All Q-wave Endeavor (n=758) Taxus (n=749)
    35. 35. Endeavor IV Death and MI at 12 months Card Death Non-Q Rate 1.1% 1.1% P =1.000 P =1.000 P =1.000 P =0.131 0.5% 0.5% 2.6% 1.6% P =0.208 0.3% 0.1% 1.3% 2.4% Death All MI All Q-wave Endeavor (n=749) Taxus (n=741)
    36. 36. Endeavor IV Target Vessel Revascularization Endeavor (41/758) Taxus (37/749) Endeavor (47/749) Taxus (50/741) P = 0.728 9 months 12 months Rate P = 0.753 5.4% 4.9% 6.3% 6.7%
    37. 37. Endeavor IV Target Lesion Revascularization Endeavor (31/758) Taxus (20/749) Endeavor (34/749) Taxus (24/741) P = 0.154 9 months 12 months Rate P = 0.228 4.1% 2.7% 4.5% 3.2%
    38. 38. Endeavor IV Relative Changes in Clinical Endpoints from 9 to 12 Months TVR Percent Increase 17% 31% 37% 17% 10% 19% 25% 50% TVF TLR Non TL-TVR
    39. 39. Endeavor IV ALL TLR Events at 12 months All Clinically Driven Non-clinically Driven TLR Rate 44 40 34 24 10 16 P =0.737 P =0.228 P =0.241 Endeavor (n=749) Taxus (n=741)
    40. 40. Endeavor IV TVR by Angiographic Follow-up at 12 months TVR Rate 14/141 9/133 33/608 41/608 Endeavor Taxus Endeavor Taxus Angiographic Follow-up Clinical Follow-up P =0.389 P =0.401 9.9%
    41. 41. Endeavor IV TLR by Angiographic Follow-up at 12 months TLR Rate 12/141 4/133 22/608 20/608 Endeavor Taxus Endeavor Taxus Angiographic Follow-up Clinical Follow-up P =0.070 P =0.875
    42. 42. Endeavor IV TVF Free Survival to 360 days Freedom from TVF 100% 85% 0 30 60 90 120 150 180 210 240 270 300 330 360 Time after Initial Procedure (days) 90% 95% TVF-free 92.3% 90.6% 0.243 Endeavor Taxus P (log rank) Taxus Endeavor
    43. 43. Endeavor IV Cardiac Death/MI Free Survival to 360 days Freedom from CD/MI 100% 95% 97% 98% Time after Initial Procedure (days) 0 30 60 90 120 150 180 210 240 270 300 330 360 99% 96% Taxus Endeavor CD/MI-free 97.9% 97.0% 0.253 Endeavor Taxus P (log rank)
    44. 44. Endeavor IV TVR Free Survival to 360 days Freedom from TVR 100% 90% 95% 0 30 60 90 120 150 180 210 240 270 300 330 360 Time after Initial Procedure (days) Taxus Endeavor TVR-free 93.7% 93.3% 0.727 Endeavor Taxus P (log rank)
    45. 45. Endeavor IV TLR Free Survival to 360 days Freedom from TLR 100% 90% 95% 0 30 60 90 120 150 180 210 240 270 300 330 360 Time after Initial Procedure (days) Taxus Endeavor TLR-free 95.5% 96.8% 0.195 Endeavor Taxus P (log rank)
    46. 46. Endeavor IV - Diabetics TVF and TLR at 12 months Rate 20/233 24/223 16/233 13/223 Endeavor Taxus Endeavor Taxus P =0.526 P =0.704 8.6% TVF TLR 477 diabetics (30.8% of E IV patients)
    47. 47. Endeavor IV TVF (9M) – Post Hoc Subgroup Analysis Diabetes Non-diabetes RVD  2.5mm >2.5 <3.0mm  3.0mm Lesion Length  10mm >10 <20mm  20mm Single Stent Multiple Stents Favors Endeavor Favors Taxus 0.1 1 10 Risk Ratio [95% CI] Risk Ratio Endeavor Taxus P-Value Interaction 14.7% (11) 13.6% (6) 0.93 0.873 6.1% (40) 6.1% (43) 1.01 10.9% (12) 5.5% (5) 0.50 6.6% (27) 7.9% (34) 1.19 0.430 6.6% (15) 4.3% (10) 0.65 6.6% (13) 5.4% (11) 0.81 6.2% (18) 7.0% (21) 1.13 0.759 8.8% (23) 7.1% (18) 0.81 6.7% (35) 6.1% (32) 0.91 0.989 8.4% (19) 7.7% (18) 0.91
    48. 48. Endeavor IV Cardiac Death/MI (9M) – Post Hoc Subgroup Analysis Diabetes Non-diabetes RVD  2.5mm >2.5 <3.0mm  3.0mm Lesion Length  10mm >10 <20mm  20mm Single Stent Multiple Stents Favors Endeavor Favors Taxus 0.1 1 10 Risk Ratio [95% CI] Risk Ratio Endeavor Taxus P-Value Interaction 5.3% (4) 4.5% (2) 0.85 0.844 2.4% (16) 1.7% (12) 0.70 5.5% (6) 1.1% (1) 0.20 2.0% (8) 2.8% (12) 1.42 0.849 2.6% (6) 0.4% (1) 0.16 3.1% (6) 2.0% (4) 0.64 1.7% (5) 2.7% (8) 1.55 0.429 3.4% (9) 0.8% (2) 0.23 3.3% (17) 2.3% (12) 0.71 0.927 1.3% (3) 0.9% (2) 0.64
    49. 49. Endeavor IV TVR (9M) – Post Hoc Subgroup Analysis Diabetes Non-diabetes RVD  2.5mm >2.5 <3.0mm  3.0mm Lesion Length  10mm >10 <20mm  20mm Single Stent Multiple Stents Favors Endeavor Favors Taxus 0.1 1 10 Risk Ratio [95% CI] Risk Ratio Endeavor Taxus P-Value Interaction 10.7% (8) 9.1% (4) 0.85 0.516 3.9% (26) 5.1% (36) 1.30 5.5% (6) 4.4% (4) 0.81 5.1% (21) 6.0% (26) 1.17 0.415 4.4% (10) 4.3% (10) 0.97 4.1% (8) 4.9% (10) 1.20 4.5% (13) 4.7% (14) 1.04 0.791 6.1% (16) 6.7% (17) 1.10 3.8% (20) 4.4% (23) 1.15 0.789 7.5% (17) 7.7% (18) 1.02
    50. 50. Endeavor IV TLR (9M) – Post Hoc Subgroup Analysis Diabetes Non-diabetes RVD  2.5mm >2.5 <3.0mm  3.0mm Lesion Length  10mm >10 <20mm  20mm Single Stent Multiple Stents Favors Endeavor Favors Taxus 0.1 1 10 Risk Ratio [95% CI] Risk Ratio Endeavor Taxus P-Value Interaction 6.7% (5) 9.1% (4) 1.36 0.616 1.8% (12) 3.7% (26) 2.03 3.6% (4) 4.4% (4) 1.21 2.7% (11) 4.4% (19) 1.64 .0481 2.2% (5) 3.0% (7) 1.36 1.5% (3) 3.9% (8) 2.56 2.4% (7) 4.0% (12) 1.66 0.514 3.8% (10) 4.3% (11) 1.13 1.3% (7) 3.3% (17) 2.43 0.149 5.8% (13) 6.0% (14) 1.04
    51. 51. Endeavor IV at 12 months Multivariate TLR Predictors for All patients P-Value Odds Ratio Multiple Logistic Regression 0.002 3.11 [1.502,6.443] Multiple vs. Single stents 0.032 1.83 [1.055,3.186] LAD vs. Non LAD <.001 2.79 [1.604,4.867] Diabetes 0.196 1.42 [0.834,2.420] Taxus vs. Endeavor
    52. 52. Endeavor IV at 12 months Multivariate TLR Predictors for Endeavor and Taxus P-Value Odds Ratio Endeavor MV TLR Predictors 0.015 2.49 [1.196,5.136] Angiography FU 0.005 3.11 [1.502,6.443] Multiple vs. Single stents 0.013 1.06 [1.012,1.110] Age 0.004 3.76 [1.518,9.318] Diabetes P-V alue Odds Ratio Taxus MV TLR Predictors
    53. 53. Endeavor IV Conclusions <ul><li>Reduced peri-procedural non-Q MIs, and a similar overall safety profile (death, Q-MI, and stent thrombosis) through 12 months follow-up </li></ul><ul><li>Higher angiographic late loss at 8 months follow-up </li></ul><ul><li>Similar TVF (1 ry endpoint) through 12 months follow-up </li></ul><ul><li>Similar TVR/TLR in subsets of interest (including diabetics) through 12 months follow-up, especially in the clinical FU patient cohort </li></ul>The Endeavor DES, compared with the Taxus DES, demonstrated…

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