Two-Year Extended Follow-up in Patients Receiving a Zotarolimus-eluting Stent in the E-Five Registry Martin T. Rothman, Ian T. Meredith, Keyur Parikh, Peter Sick, Fausto Feres, Chaim Lotan, For the E-FIVE Registry Investigators

E-Five Registry Prospective, Multicenter Registry PI: Chaim Lotan, Ian Meredith and Martin Rothman Single and Multiple Coronary Artery Lesions Stent Diameters: 2.25-4.0 mm Stent Length: 8/9-30 mm N = 8,000 patients N = 2000 at 2 years 200 sites Europe, Asia Pacific, Israel, New Zealand, South America Clinical/MACE 30d 6mo 12mo 2yr* Primary Endpoint: MACE at 12 months Secondary Endpoints: MACE at 30 days and 6 mo, stent thrombosis, procedure success rate; device success rate; lesion success rate Drug Therapy: ASA and clopidogrel ≥3 months Zotarolimus Dose: 10 g per mm stent length *Limited number of centers.

E-Five Registry Background Drug-eluting stents for PCI effectively reduce restenosis rates in patients with symptomatic ischemic heart disease and de novo coronary artery lesions. Long-term safety and late stent thrombosis rates remain a concern. The Endeavor zotarolimus-eluting stent (ZES) has been found to successfully treat patients with a range of clinical and angiographic characteristics. Long-term follow-up in real-world populations is essential to establish the safety of the Endeavor ZES in patients with both simple and complex lesions. Extended two year follow-up was planned for a prespecified subset of approximately 2000 patients undertaken in 26 centers to determine the durability of the safety and efficacy of the Endeavor ZES in the “real world” patient population of the E-Five study.

E-Five Registry Data System and Quality Control Clinical Event Committee: Cardialysis (Rotterdam, The Netherlands) Independent adjudication of all reported MACE and stent thrombosis (protocol and ARC definite/probable) events Data Monitoring: 10% monitoring aimed at detecting underreporting of events (CRO and Medtronic) Electronic Data Collection (KIKA, Boston, MA)

E-Five Registry Clinical Outcomes to 1 Year All Patients 30 days 1 Year n = 7832 Death (all) – % (n) 0.6 (52) 2.4 (191) Cardiac 0.6 (46) 1.7 (135) MI (all) – % (n) 0.9 (75) 1.6 (128) Q Wave 0.2 (16) 0.4 (31) Non Q wave 0.7 (59) 1.3 (98) Death (cardiac) + MI (all) – % (n) 1.4 (115) 3.0 (238) ARC def/prob ST – % (n) 1.1 (88) 0-30 days 0.8 (59) 31-365 days TLR – % (n) 0.4 (35) 4.5 (349) TVR (non-TL) – % (n) 0.0 (4) 0.7 (52) TVR – % (n) 0.5 (38) 4.9 (387) MACE – % (n) 1.6 (135) 7.5 (587) TVF – % (n) 1.6 (132) 7.2 (565)

E-Five Registry Two Year Follow-up Cohort Country Patients Total 2116 Brazil 100 China 40 Germany 199 Greece 138 India Italy 480 Latvia Malaysia 176 Netherlands Portugal Spain 256 Switzerland UK 64 Uruguay 87 Total 2116

E-Five Registry Patient Demographics All Patients N = 8314 2-Yr Subset N = 2116 Male (%) 76.7 77.3 Age (years) 63.3±11.1 62.1±11.0 Prior MI (%) 32.2 35.3 Non Q Wave 12.2 12.8 Q Wave 21.3 23.5 Prior PCI (%) 25.3 24.1 Prior CABG (%) 7.5 6.9 Diabetes Mellitus (%) 32.7 30.1 Acute Coronary Syndrome (%) 47.8 40.7 Recent MI (< 72 hours) (%) 13.9 11.4 Unstable Angina (%) 33.9 29.3 Moderate/Severe Renal Impairment* (%) 6.5 5.6 * Serum creatinine ≥ 140 µmol/L and no renal transplant.

E-Five Registry Clinical Outcomes to 2 Years (Prespecified Subset) 2 Years n = 2054 Death (all) – % (n) 1.7 (36) 2.9 (60) Cardiac 1.2 (25) 1.5 (31) MI (all) – % (n) 1.5 (30) Q Wave 0.2 (5) 0.3 (7) Non Q wave 1.0 (20) 1.1 (23) Death (cardiac) + MI (all) – % (n) 2.3 (48) 2.8 (57) ARC Def/ Prob ST – % (n) 0.6 (13) 0.7 (15) 0-30 days 0.5 (10) 31-365 days 0.1 (3) 366-730 days 0.1 (2) TLR – % (n) 4.5 (94) 5.1 (105) TVR (non-TL) – % (n) 0.9 (18) 1.0 (21) TVR – % (n) 5.2 (108) 5.9 (121) MACE – % (n) 6.7 (140) 8.5 (174) TVF – % (n) 6.7 (141) 7.9 (162)

E-Five Registry Clinical Outcomes to 2 Years (Prespecified Subset) 8.5% E-Five (n=2054) Death Cardiac Death MI Protocol ST ARC ST Def/Prob TLR TVR TVF MACE n=60 n=31 n=30 n=15 n=15 n=105 n=121 n=162 n=174 n = number of events

E-Five Registry Adverse Events Between 1-2 Years (Prespecified Subgroup) Year 1 Year 2 TLR Death Cardiac Death MI Protocol ST ARC Def/Prob ST TVR TVF MACE

Cumulative Incidence MACE Time after initial Procedure (days) E-Five Registry Cumulative Incidence of MACE to 2 Years (Prespecified Subset) Cumulative Incidence MACE Time after initial Procedure (days) 0% 2% 4% 6% 8% 10% 90 180 270 360 450 720 E-Five 540 630 Type 90 180 270 360 450 540 630 720 730 # at Risk 2116 2085 2067 2030 1980 1936 1917 1906 1889 1791 # of Events 12 15 36 40 25 7 8 %CI 0.6% 1.8% 3.6% 5.5% 6.7% 7.0% 7.4% 8.0% 8.3%

Cumulative Incidence TLR Time after initial Procedure (days) E-Five Registry Cumulative Incidence of TLR to 2 Years (Prespecified Subset) Cumulative Incidence TLR Time after initial Procedure (days) 0% 2% 4% 6% 8% 10% 90 180 270 360 450 720 E-Five 540 630 Type 90 180 270 360 450 540 630 720 730 # at Risk 2116 2098 2082 2046 1995 1956 1933 1924 1913 1816 # of Events 9 32 34 12 2 4 3 %CI 0.0% 0.8% 2.3% 3.9% 4.5% 4.6% 4.8% 4.9% 5.0%

E-Five Registry Cumulative Incidence of ARC Def/Prob ST to 2 Years (Prespecified Subset) Cumulative Incidence ARC Def/Prob Time after initial Procedure (days) 0% 2% 4% 6% 8% 10% 90 180 270 360 450 720 Cumulative Incidence ARC Def/Prob ST E-Five 540 630 Type 90 180 270 360 450 540 630 720 730 # at Risk 2116 2097 2091 2086 2070 2041 2020 2014 2003 1906 # of Events 1 %CI 0.0% 0.5% 0.6% 0.7%

Percent of patients on DAPT at: E-Five Registry Dual Antiplatelet Therapy (DAPT) Usage (Prespecified Subset) Percent of patients on DAPT at: 6 months 12 months 24 months 81.8% (1705/2084) 52.6% (1077/2049) 22.1% (439/1989)

E-Five Registry Conclusions (Prespecified Subset) The Endeavor ZES was associated with a low and durable TLR rate regardless of lesion complexity with very few events between 1-2 years (Δ 0.6%). In this prespecified subset of patients followed to 2 years, the cardiac death, MI and ST rates (protocol and ARC def/prob) were stable. These results are consistent with the safety and efficacy findings from the ENDEAVOR Clinical Program despite the “real world” nature of the patient population.