ENDEAVOR II Five-Year Clinical Follow-up Ian T. Meredith, MBBS, PhD MonashHEART Monash Medical Centre Melbourne, Australia On Behalf of the Endeavor II Investigators

Potential Conflicts Of Interest Speaker’s name: Ian T. Meredith I have the following potential conflicts of interest to report: Research contracts Consulting Employment in industry Stockholder of a healthcare company Owner of a healthcare company Other(s) I do not have any potential conflict of interest 2

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

Polymer and Drug Matrix PC overspray (~0.1 µm thick) Stent strut Post-elution ~1-µm coating of PC polymer Drug layer 90% zotarolimus (10 µg/mm) 10% PC (~2–3 µm thick) Stent strut PC basecoat (~1 µm thick) ENDEAVOR CYPHER TAXUS Liberté XIENCE V Strut Thickness 91 µm 140 µm 97 µm 81 µm Polymer Thickness 4.8 µm 12.6 µm 17.8 µm 7.8 µm

ENDEAVOR II Double-Blind, Randomized Clinical Trial vs Driver PI: Jean Fajadet, William Wijns et. al. Single De Novo Native Coronary Artery Lesions Reference Vessel Diameter 2.25 mm-3.5 mm Lesion Length: 14-27 mm Pre-dilatation required N = 1,200 patients 72 sites Europe, Asia Pacific, Israel, New Zealand and Australia Endeavor Stent Active Arm n=600 Driver Stent Control Arm n=600 Clinical/MACE 30d 6mo 8mo 9mo 12mo 2yr 3yr 4yr 5yr Angiography/IVUS Angio = first 600 pts IVUS = first 300 pts (plus IVUS for overlapping stents) Primary Endpoint: TVF at 9 months Secondary Endpoints: MACE at 30 days and 9 months, BR at 8 months Drug Therapy: ASA and Clopidogrel >3 months Zotarolimus Dose: 10 g per mm stent length Fajadet et al. Circulation. 2006;114:98-806.

ENDEAVOR Clinical Program ENDEAVOR I First in Human 5 Years n = 97/100 (97%) ENDEAVOR II Double-blind Randomized Trial 5 Years n = 577/598 (97%) ENDEAVOR II CA Continued Access Registry 4 Years n = 287/296 (97%) ENDEAVOR III Confirmatory Trial vs. Cypher 4 Years n = 307/323 (95%) ENDEAVOR IV Confirmatory Trial vs. Taxus 2 Years n = 742/773 (96%) ENDEAVOR PK Pharmacokinetic Trial 2 Years n = 42/43 (98%) E-Five Post Market Surveillance 2 Years n = 2054/2116 (97%)

ENDEAVOR II Patient Flowchart Patients Enrolled N = 1197 Endeavor Driver n = 599 Randomized Angio F/U (8 mo) 264/298 88.6% Angio F/U (8 mo) 265/302 87.7% Clinical Follow-up Clinical Follow-up (1yr) 590/598 98.7% (2yr) 588/598 98.3% (3yr) 585/598 97.8% (4yr) 583/598 97.5% (5yr) 577/598 96.5% (1yr) 590/599 98.5% (2yr) 588/599 98.2% (3yr) 587/599 98.0% (4yr) 584/599 97.5% (5yr) 582/599 97.2%

ENDEAVOR II TVF and TLR at 9 Months Primary Endpoint Target Vessel Failure* TLR P<0.001 P<0.001 47% 61% Driver Endeavor Driver Endeavor *Target Vessel Failure is a composite of target vessel revascularization, MI, or cardiac death.

Time after Initial Procedure (years) ENDEAVOR II Cumulative Incidence of TVF to 5 years Endeavor Driver Log rank P = <0.001 24.3% 15.3% 30% 25% 20% 15% 10% 5% 0% 9m 1 2 3 4 5 Time after Initial Procedure (years) Cumulative Incidence TVF Δ 7.1% Δ 9.0% Days 270 360 720 1080 1440 1800 Endeavor 597 584 541 525 515 497 487 % CI 2.2 7.9 10.0 11.0 12.6 13.5 15.3 Driver 596 580 501 465 446 435 2.7 15.0 16.5 19.6 21.2 22.4 24.3

Cumulative Incidence TLR Time after Initial Procedure (years) ENDEAVOR II Cumulative Incidence of TLR to 5 years Cumulative Incidence TLR Log rank P = <0.001 16.5% 7.4% 30% Time after Initial Procedure (years) Endeavor Driver 25% 20% 15% 10% 5% 0% 9m 1 2 3 4 5 Δ 7.2% Δ 9.1% Days 270 360 720 1080 1440 1800 Endeavor 597 595 552 538 529 515 505 % CI 0.3 4.6 6.0 6.5 7.2 7.4 Driver 596 504 489 474 456 445 0.2 11.9 13.2 14.2 14.8 15.9 16.5

ENDEAVOR II TLR at 5 years TLR (%) P<0.001 P<0.001 P<0.001

ENDEAVOR II Summary of Clinical Events at 5 years Endeavor N = 598 Driver N = 599 P Value Death (all) - % (n) 6.2 (36) 7.6 (44) 0.418 Cardiac 3.1 (18) 3.6 (21) 0.745 MI (all) – % (n) 3.8 (22) 4.8 (28) 0.470 Q Wave -% (n) 0.3 (2) 1.2 (7) 0.178 Non Q Wave - % (n) 3.5 (20) 1.000 Death (cardiac) + MI (all) – % (n) 6.6 (38) 8.4 (49) 0.265 TLR – % (n) 7.5 (43) 16.3 (95) <0.001 TVR (non-TL) – % (n) 4.3 (25) 0.188 TVR – % (n) 10.7 (62) 20.1 (117) MACE – % (n) 15.4 (89) 24.6 (143) TVF – % (n) 24.4 (142) Table 4h

ENDEAVOR II Clinical Performance at 5 years (%) P<0.001 P<0.001 38% TVF 54% TLR

ENDEAVOR II Summary of ARC Stent Thrombosis to 5 years Endeavor Driver n = 599 P Value Stent Thrombosis (ARC Def/prob) - %(n) 0.9 (5) 1.7 (10) 0.299 Early: 0-30 days 0.5 (3) 1.2 (7) 0.342 Late: 31-360 days 0.2 (1) 1.000 Very Late: 361-1800 days 0.3 (2)

Pivotal Trials TLR: DES Arms Rates of TLR Over Time ENDEAVOR II (n=577/598) SIRIUS (n=501/533) TAXUS IV (n=618/662) 9.4 9.1 7.9 7.8 7.5 7.2 7.2 6.5 6.8 6.9 5.9 6.3 TLR (%) TLR (%) TLR (%) 5.6 4.9 4.4 1 2 3 4 5 1 2 3 4 5 1 2 3 4 5 Years of Follow-up Years of Follow-up Years of Follow-up 5 Year Clinical Results of TAXUS IV, Stone, ACC 2007 5 year Outcomes in the Sirius Trial, Weisz et al. JACC Vol. 53, No. 17, 2009 Results come from separate clinical trials. Data may differ in a head-to-head comparison.

ENDEAVOR II Conclusions Sustained clinical benefit out to 5 years with a excellent safety profile with no new (ARC) stent thrombosis events These long term outcomes could be due in part to the unique biocompatible nature of the PC polymer The Endeavor ZES when compared with the Driver stent demonstrated: