ENDEAVOR IV: 5 Year Final Outcomes David E. Kandzari and Martin B. Leon for the ENDEAVOR IV Trial Investigators

ENDEAVOR IV Study Objectives (2005) To compare safety and efficacy outcomes measured by target vessel failure (non-inferiority design) among patients randomized to the Endeavor ZES and Taxus PES To determine whether 8 month angiographic outcomes (in-segment late loss) with the Endeavor ZES are non-inferior to the FDA-approved Taxus PES

ENDEAVOR IV Outstanding Questions (2011) Does higher late loss with Endeavor ZES stent (compared with Taxus PES) translate into greater late-term TLR beyond the period of angiographic follow-up? What are the late-term safety outcomes of Endeavor ZES and Taxus PES? Are Endeavor ZES outcomes consistent with late-term follow up observed in the overall Endeavor Clinical Trial program?

Endeavor Global Clinical Program Enrollment Complete / In Follow Up 1yr 2yr 3yr 4yr 5yr ENDEAVOR I Single Arm First-in-Man (n = 100) 5yr ENDEAVOR II 1:1 RCT vs BMS (E = 598, D = 599) PK (n = 106) 5yr ENDEAVOR II CA Continued Access Single Arm (n = 296) 5yr ENDEAVOR III 3:1 RCT vs Cypher® (E = 323, C = 113) 5yr ENDEAVOR IV 1:1 RCT vs Taxus® (E = 773, T = 775) 5yr ENDEAVOR PK Pharmacokinetic Study (n = 43) 5yr ENDEAVOR Japan Single Arm (n = 99) 4yr E-FIVE Open Label Single Arm (n = 8300) 2yr PROTECT 1:1 RCT vs Cypher (E = 4400, C = 4400) PROTECT CA Continued Access Single Arm (n ≥ 1000) EDUCATE 1:1 RCT 12 vs 30 months DAPT (n = 2000–4000) ENDEAVOR SVS Small Vessel Single Arm (n ≈ 250) Enrollment ongoing E-Japan PMS Post Mkt Registry Single Arm (n ≈ 2000)

ENDEAVOR IV Multicenter Randomized Trial vs Taxus PI: M. Leon and D. Kandzari Single De Novo Native Coronary Artery Lesions Reference Vessel Diameter: 2.5 – 3.5 mm Lesion Length: ≤ 27 mm Pre-dilatation required Endeavor Stent N = 774 N = 1548 patients 1:1 Randomization 80 US sites Taxus Stent N = 774 Clinical endpoints 30d 6mo 8mo 9mo 12mo 2yr 3yr 4yr 5yr Angio/IVUS endpoints QCA and IVUS Subset (328 total = 21.2%) Primary Endpoint: TVF (cardiac death, MI, TVR) at 9mo Secondary Endpoints: In-segment % DS at 8mo; TLR and TVR at 9mo Drug Therapy: ASA and clopidogrel/ticlopidine ≥ 6mo

ENDEAVOR IV Patient Flowchart Patients Enrolled N = 1548 Endeavor Taxus N = 775 Randomized 1:1 Angio F/U (8mo) 144/164 87.8% Angio F/U (8mo) 135/164 82.3% Clinical F/U Clinical F/U 1Yr 761/773 98.4% 2Yr 756/773 97.8% 3Yr 747/773 96.6% 4Yr 732/773 94.7% 5Yr 722/773 93.4% 1Yr 758/775 97.8% 2Yr 754/775 97.3% 3Yr 743/775 95.9% 4Yr 728/775 93.9% 5Yr 718/775 92.6% UC200805003dEN 6

ENDEAVOR IV Selected Baseline Characteristics Endeavor n = 773 Taxus P value Age (years, mean ± SD) 63.5 ± 11.1 63.6 ± 11.0 0.930 Males (%) 66.9 68.5 0.514 Prior MI (%) 21.1 23.2 0.324 Diabetics (%) 31.2 30.5 0.783 Unstable angina (%) 51.6 49.9 0.567 RVD (mm) 2.73 ± 0.47 2.70 ± 0.46 0.197 Lesion length (mm) 13.41 ± 5.67 13.80 ± 6.09 0.199 B2/C lesions (%) 69.6 70.9 0.578 7

ENDEAVOR IV Clinical Outcomes at 5 Years Events % (n) Endeavor n = 722 Taxus n = 718 P value Death (all) 10.0 (72) 9.1 (65) 0.59 Cardiac 4.3 (31) 3.8 (27) 0.69 MI (all) 2.6 (19) 6.0 (43) 0.002 Q Wave 0.6 (4) 0.7 (5) 0.75 Non Q wave 2.1 (15) 5.3 (38) 0.001 Death (cardiac) + MI (all) 6.4 (46) 9.2 (66) 0.049 Stent Thrombosis (def/prob) 1.4 (10) 1.9 (14) 0.42 Early (≤ 30 days) 0.4 (3) 0.1 (1) 0.62 Late (31-360 days) 0.0 (0) 0.12 Very Late (361-1800 days) 1.8 (13) 0.012 TLR 7.8 (56) 8.4 (60) 0.70 TVR (non-TL) 6.8 (49) 9.5 (68) 0.07 TVR 12.7 (92) 15.0 (108) 0.22 MACE 17.9 (129) 20.3 (146) 0.25 TVF 17.3 (125) 21.3 (153) 0.06 8

Cumulative Incidence for TVF Time After Initial Procedure (Years) ENDEAVOR IV Cumulative Incidence of Target Vessel Failure to 5 Years Endeavor ZES Log Rank P = 0.061 25% £ 1 year E-ZES 6.6% PES 9.8% >1 year to 5 years E-ZES 10.6% PES 11.5% Taxus PES 21.1% (153) 20% 17.2% (125) 15% Cumulative Incidence for TVF 10% 7.2% 5% 6.6% 0% 9M 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 773 769 704 685 642 615 566 Taxus 775 755 695 668 627 587 549 Primary endpoint: TVF at 9-months, Pnon-inferiority < 0.001 UC200805003dEN 9 9

Cumulative Incidence for TLR Time After Initial Procedure (Years) ENDEAVOR IV Cumulative Incidence of TLR to 5 Years Endeavor ZES Log Rank P = 0.70 0.9% 10% Taxus PES £ 1 year E-ZES 4.5% PES 3.3% >1 year to 5 years E-ZES 3.2% PES 5.1% 8.6% (60) 8% 7.7% (56) 6% Cumulative Incidence for TLR 4% 2% 0% 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 773 695 661 636 594 Taxus 775 771 665 626 593 UC200805003dEN 10

ENDEAVOR IV – 5yr Follow Up TLR Rate Over Time Endeavor Taxus 73% Increase 155% Increase 8.4 7.4 7.8 7.1 6.4 5.8 6.1 4.5 4.5 TLR Rate (%) 3.3 1 2 3 4 5 1 2 3 4 5 Years of Follow-up Years of Follow-up Values are the event rates. 11

Endeavor Pooled Efficacy Analysis Cumulative Incidence of TLR to 5 Years Endeavor ZES 25% Driver BMS Log rank P < 0.001 £ 1 year E-ZES 5.4% >1 year to 5 years E-ZES 2.6% 20% BMS 13.2% BMS 3.8% 16.5% 15% Cumulative Incidence of TLR 10% 7.4% 5% 0% 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 2132 2130 1913 1853 1797 1727 Events n (%) 2 (0.1) 113 (5.4) 129 (6.2) 139 (6.7) 146 (7.1) 151 (7.4) Driver 596 595 489 474 456 445 1 (0.2) 77 (13.2) 83 (14.2) 86 (14.8) 92 (15.9) 95 (16.5) 12 12 12

ENDEAVOR IV Cumulative Incidence of Cardiac Death/MI to 5 Years Endeavor ZES Log Rank P = 0.048 10% Taxus PES £ 1 year E-ZES 2.1% PES 3.3% >1 year to 5 years E-ZES 4.3% PES 5.9% 9.1% (66) 8% 6.4% (46) 6% Cumulative Incidence of Cardiac Death/MI (%) 4% 2% 0% 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 773 769 725 696 675 634 Taxus 775 758 715 684 651 621 UC200805003dEN 13 13

ENDEAVOR IV Cumulative Incidence of MI to 5 Years Log Rank P = 0.002 Endeavor ZES Log Rank P = 0.002 10% Taxus PES £ 1 year E-ZES 1.6% PES 2.6% >1 year to 5 years E-ZES 1.0% PES 3.4% 8% 6.0% (43) 6% Cumulative Incidence of Cardiac Death/MI (%) 4% 2.6% (19) 2% 0% 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 773 769 725 696 675 634 Taxus 775 758 715 684 651 621 UC200805003dEN 14 14 14

ENDEAVOR IV – 5yr Follow Up All Non-Q MIs CKMB Rises (xULN) Endeavor DES (n=722) Taxus DES (n=718) 17/34 (50%) of Taxus Non-Q MIs with CKMB rises ≥10X ULN Number Patients ≥5X<8X ≥8X<10X ≥10X

Time After Initial Procedure (Years) ENDEAVOR IV Dual Antiplatelet Therapy Adherence to 5 Years Endeavor ZES 92.1% 91.4% Taxus PES P = 0.02 71.3% 57.6% 54.5% P = 0.03 65.4% 52.1% 49.0% 47.9% Adherence to DAPT 54.5% 57.2% 48.2% 45.8% 41.8% Time After Initial Procedure (Years) DAPT protocol ≥ 6 months Physicians and patients unblinded at 12 months UC200805003dEN 16 16 16

ENDEAVOR IV Cumulative Incidence of ARC ST Def/Prob to 5 Years Endeavor ZES Log Rank P = 0.42 5% £ 1 year E-ZES 1.0% PES 0.1% >1 year to 5 years E-ZES 0.4% PES 1.8% Taxus PES 4% 3% Cumulative Incidence for ARC Definite/Probable Stent Thrombosis 2.0% (14) 2% 1.3% (10) 1% 0% 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 773 731 704 683 642 Taxus 775 774 733 706 674 643 UC200805003dEN 17 17

ENDEAVOR IV Cumulative Incidence of Very Late ST to 5 Years 5% Endeavor ZES Log Rank P = 0.012 Taxus PES 4% 3% Cumulative Incidence of ARC Def/Prob Very Late Stent Thrombosis (%) 2% 1.8% (13) 1% 0.4% (3) 0% 1 2 3 4 5 Time After Initial Procedure (Years) Endeavor 737 710 689 648 Taxus 734 707 675 644 UC200805003dEN 18 18

ENDEAVOR IV TLR, Cardiac Death/MI and MACE at 1 and 5 Years TLR Δ 10.5% vs. 13.4% Δ 3.3% vs. 5.1% Δ 4.3% vs. 5.9% 1 Year 5 Years

ENDEAVOR IV Conclusions at 5 Years In a trial designed to compare a clinical composite endpoint, a trend toward lower target vessel failure was observed with Endeavor ZES compared with Taxus PES at 5 years Despite initially higher angiographic late loss with Endeavor ZES, Rates of TLR beyond period of protocol-mandated angiographic surveillance remain stable with Endeavor ZES Absolute differences between DES in clinical restenosis temporally decrease, resulting in crossover of event curves favoring Endeavor ZES at 5 years Recognizing limitations in sample size, late term (5y) follow up of the Endeavor stent demonstrates Durability in efficacy (TLR) Compared with Taxus PES, significantly lower rate of VLST with Endeavor ZES Compared with Taxus PES, emerging differences in MI and cardiac death/MI achieving statistical significance Late term EIV outcomes with the Endeavor ZES parallel the consistent safety and efficacy observed across the Endeavor Clinical Trials Program