- Endeavor IV was a randomized trial comparing the zotarolimus-eluting Endeavor stent to the paclitaxel-eluting Taxus stent. - The primary endpoint was target vessel failure at 9 months, with a pre-specified non-inferiority margin of 3.8%. - 1,548 patients at 80 sites in the US were randomized 1:1 to receive either the Endeavor or Taxus stent. Follow-up was planned through 5 years.

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. 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. Endeavor DES System PC Technology Drug: Zotarolimus Stent Delivery System Driver Cobalt Alloy Stent

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

8. Preserved Endothelial Function In Vivo Assessment of Endothelial Function in Porcine Models: eNOS Staining Endeavor Driver Immunohistochemistry Staining for Presence of eNOS

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. 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. 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

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%)

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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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