Martin B. Leon, MD for the Endeavor IV investigators Columbia University Medical Center Cardiovascular Research Foundation New York City Monday, September 22, 2009 Three-Year Follow-up from a Prospective Randomized Trial Comparing a Zotarolimus-Eluting Stent and a Paclitaxel-Eluting Stent in Patients with Coronary Artery Disease ENDEAVOR IV

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 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 ENDEAVOR IV – 3yr FU Single De Novo Native Coronary Lesion Vessel Diameter: 2.5–3.5 mm Lesion Length: ≤ 27 mm Pre-dilatation required 30d 6mo 4yr 3yr 2yr 9mo 12mo 8mo 5yr Clinical/MACE Angiography/IVUS QCA and IVUS Subset (328 total = 21.2%) Clinical Trial Design PIs: Martin B. Leon and David E Kandzari 1:1 randomization N = 1,548 patients 80 sites US Endeavor Stent n = 774 Taxus Stent n = 774

Endeavor IV - Top Enrollers PatientsPatients C. O’Shaughnessy Elyria Memorial Hospital, Elyria, OH 119 J. Patterson Forsyth Medical Center, Winston-Salem, NC 29 P. Overlie Lubbock heart Hospital, Lubbock, TX 95 M. Sketch Duke University Medical Center, Durham, NC 28 B. McLaurin Anderson Medical Center, Anderson, SC 63 M. Leon Columbia Presbyterian Center NY, NY, NY 28 S. Solomon Methodist Hospital Houston, Houston, TX 59 P. Coleman Sutter Medical Center, Santa Rosa, CA 27 J. Douglas Emory Clinic, Atlanta, GA 51 R. Stoler Baylor Heart & Vascular, Dallas, TX 26 M. Ball Heart Center of Indiana, Indianapolis, IN 51 S. Papadakos New York Hospital of Queens, Flushing, NY 26 R. Caputo St. Joseph Hospital health Center, Syracuse, NY 50 J. Singh Barnes Jewish, St. Louis, MO 23 A. Jain Washington Hospital Healthcare, Fremont, CA 47 D. Pinto Beth Israel Hospital, Boston, MA 23 T. Tolleson Mother Francis health System, Tyler, TX 45 B. Rutherford St. Luke’s Hospital, Kansas City, MO 23 B. Reen Prsbyterian hospital, Charlotte, NC 44 V. Chilakamarri Lutheran Hospital of IN, Fort Wayne, IN 22 H. Liberman Emory Crawford Long, Atlanta, GA 36 R. Prashad Ocala Regional Medical Center, Ocala, FL 22 H. Wilson Carolinas Medical Center, Charlotte, NC 30 T. Bass University of Florida, Jacksonville, FL 22 P. Bajwa Nebraska Heart Institute, Lincoln, NE 29 T. Sacchi NY Methodist/Cornell Heart Center, Brooklyn, NY 20

ENDEAVOR IV – 3yr FU Patient Demographics Endeavor (773 pts) Taxus (775 pts) P value Age (in years) 63.5 ± ± Men (%) Diabetes (%) IDDM (%) IDDM (%) Prior MI (%) Angina – Stable (%) Unstable (%) MI (%)

Endeavor (773 lesions) Taxus (775 lesions) P value CAD – Single Vessel (%) Vessel Location (%) LAD ACC/AHA Lesion Class B 2 /C QCA RVD (mm) 2.73 ± ± MLD (mm) 0.96 ± ± % DS ± ± Lesion Length (mm) ± ± ENDEAVOR IV – 3yr FU Lesion Characteristics (QCA)

Patients Enrolled N = 1548 Randomized Endeavor n = 773 Clinical F/U (12 mo) 756/ % Taxus n = 775 Clinical F/U (12 mo) 757/ % Clinical F/U (36 mo) 734/ % Clinical F/U (36 mo) 734/ % ENDEAVOR IV – 3yr FU Patient Flow Chart

ENDEAVOR IV – 3yr FU TVF to 36 months Endeavor Taxus % 15% 10% 5% 0% Cumulative Incidence for TVF Time after Initial Procedure (days) Values are the KM estimates P values were calculated by Log Rank Test 1-year HR 0.79 [0.56, 1.11] P= % 7.7% ∆1.9% 3-year HR 0.77 [0.58, 0.99] P = % 12.3% ∆3.6% Endeavor Taxus

Cardiac Death/MI Rate = Endeavor (n=734) Taxus (n=734) TVFTVR P =0.608 ENDEAVOR IV – 3yr FU Primary EP TVF to 36 months RRR 23% NNT: 27 P=0.052 RRR 48% NNT: 29 P= /734118/73473/73427/73452/73480/734 Values are the event rates P values were calculated by Fisher Exact Test

ENDEAVOR IV – 3yr FU CD/MI to 36 months 10% 8% 6% 4% 0% Cumulative Incidence of Cardiac Death/MI Time after Initial Procedure (days) 2%Endeavor Taxus Values are the KM estimates P values were calculated by Log Rank Test 1-year HR 0.66 [0.35, 1.25] P=0.201∆1.0% 3.1% 2.1% 3.6% 7.1% ∆3.5% 3-year HR 0.52 [0.32, 0.82] P = Endeavor Taxus

CD/MI (%) Time after Initial Procedure (days) ENDEAVOR IV – 3yr FU CD/MI Landmark to 36 months Endeavor Taxus Values are the KM estimates P values were calculated by Log Rank Test 0.0% 2.0% 4.0% 6.0% % 4.0% ∆2.3% P = year HR 0.43 [0.22, 0.84] 3.1% 2.1% ∆1.0% 1-year HR 0.66 [0.35, 1.25] P=0.201

ENDEAVOR IV – 3yr FU MI Landmark to 36 months MI (%) Time after Initial Procedure (days) Endeavor Taxus Values are the KM estimates P values were calculated by Log Rank Test 0.0% 1.0% 2.0% 3.0% % 2.3% ∆1.6% P = year HR 0.31 [0.12, 0.86] 1 year HR 0.60 [0.29, 1.23] 2.6% 1.6% ∆1.0% P=0.154

≥5X<8X ≥8X<10X ≥10X Number Patients ENDEAVOR IV – 3yr FU All MIs CKMB Rises (xULN) 1-3 years 10/16 (63%) of Taxus MIs with CKMB rises  10X ULN 2/4 Endeavor MIs and 2/16 Taxus MIs CKMB (xULN) <5X Endeavor Taxus

Length of DAPT EndeavorTaxus P value 180 days on (%) days on (%) days on (%) days on (%) days on (%) * Physicians and patients unblinded at 12 months ENDEAVOR IV – 3yr FU DAPT to 36 months*

Rate Endeavor (n=734) Taxus (n=734) ARC Definite ARC Probable ARC Definite Probable n=6 n=11 n=1 n=5n=1 P =0.124 P =0.062 P =0.006 ENDEAVOR IV – 3yr FU ARC VLST mos RRR 91% NNT: 71 P=0.006 Values are the event rates P values were calculated by Fisher Exact Test

4% 2% 0% Time after Initial Procedure (days) Cumulative Incidence of Def/Prob Thrombosis ENDEAVOR IV – 3yr FU ARC ST Def/Prob mos (VLST) Endeavor Taxus % 1.6% ∆1.5% 1-3 year HR 0.09 [0.01, 0.71] P = Endeavor Taxus Values are the KM estimates P values were calculated by Log Rank Test

Days Endeavor Taxus Taxus VLST ( n=11) 5/11 On ASA and Plavix 4/11 on ASA 2/11 No DAPT 2/11 Resulted in a TLR 9/11 Resulted in an AMI 369 Endeavor VLST ( n=1) 1/1 No DAPT 1/1 Resulted in an AMI ENDEAVOR IV – 3yr FU Timing of ARC Def/Prob VLST 5 Taxus VLST events from 2-3 years

ENDEAVOR IV – 3yr FU TLR to 36 months 10% 8% 6% 4% 0% Cumulative Incidence for TLR Time after Initial Procedure (days) 2%Endeavor Taxus Values are the KM estimates P values were calculated by Log Rank Test 1-year HR 1.36 [0.81, 2.28] P= % 3.3% ∆1.2% 6.5% 6.1% ∆0.4% 3-year HR 1.10 [0.73, 1.65] P = Endeavor Taxus

TLR Rate 123 Years of Follow-up 123 Endeavor (Yr 3 N = 734/773) Taxus (Yr 3 N = 734/775) ENDEAVOR IV – 3yr FU TLR Rate Over Time 82% Increase 44% Increase Values are the event rates 4.5% 3.3% 5.9% 6.5% 6.0% 4.5%

5 Year Clinical Results of TAXUS IV, Stone, ACC 2007 Results come from separate clinical trials. Data may differ in a head-to-head comparison. ENDEAVOR II (n=577/598) TLR (%) Years of Follow-up Endeavor II and Taxus IV: DES Arms TLR Rates to 5 years TAXUS IV (n=618/662) TLR (%) Years of Follow-up 27% Increase 106% Increase

Subgroup Post-Hoc Analysis ENDEAVOR IV

ENDEAVOR IV – 3yr FU TVF (36 mos) – Post Hoc Analysis % (35) 21.6% (47) % (56) 13.8% (71) Risk Ratio [95% CI] Risk RatioEndeavorTaxus P-Value Interaction Diabetes Non-diabetes RVD  2.5mm >2.5 <3.0mm  3.0mm Lesion Length  10mm >10 10 <20mm  20mm Favors Endeavor Favors Taxus % (29) 19.8% (51) % (40) 14.4% (41) 14.4% (41) % (22) 13.7% (26) % (23) 18.6% (41) % (57) 14.4% (58) 14.4% (58) % (10) 17.4% (19) % (82) 14.7% (95) % (8) 25.3% (71) TVF (Target Vessel Failure) is defined as cardiac death, MI or TVR Single Stent Multiple Stents OVERALL % (99) 16.1% (118) P diff =0.052

ENDEAVOR IV – 3yr FU CD/MI (36 mos) – Post Hoc Analysis % (6) 7.3% (16) % (21) 4.1% (21) 7.0% (36) Risk Ratio [95% CI] Risk RatioEndeavorTaxus P-Value Interaction Diabetes Non-diabetes RVD  2.5mm >2.5 <3.0mm  3.0mm Lesion Length  10mm >10 10 <20mm  20mm Single Stent Multiple Stents OVERALL Favors Endeavor Favors Taxus % (5) 7.8% (20) % (14) 4.8% (14) 6.3% (18) 6.3% (18) % (8) 7.4% (14) % (4) 8.1% (18) 8.1% (18) % (21) 5.0% (21) 6.2% (25) 6.2% (25) % (2) 8.3% (9) % (25) 3.7% (25) 6.5% (42) 6.5% (42) % (2) 12.0% (9) % (27) 7.1% (52) P diff =0.005

ENDEAVOR IV – 3yr FU TVR (36 mos) – Post Hoc Analysis % (32) 15.6% (34) % (41) 8.0% (41) 8.9% (46) 8.9% (46) Risk Ratio [95% CI] Risk RatioEndeavorTaxus P-Value Interaction Diabetes Non-diabetes RVD  2.5mm >2.5 <3.0mm  3.0mm Lesion Length  10mm >10 10 <20mm  20mm Favors Endeavor Favors Taxus % (26) 14.3% (37) % (29) 10.0% (29) 10.2% (29) 10.2% (29) % (18) 9.1% (18) 7.4% (14) 7.4% (14) % (21) 9.3% (21) 14.0% (31) 14.0% (31) % (43) 10.3% (43) 9.7% (39) 9.7% (39) % (8) 9.2% (10) 9.2% (10) % (66) 9.7% (66) 9.6% (62) 9.6% (62) % (6) 18.7% (14) 18.7% (14) Single Stent Multiple Stents OVERALL % (73) 10.9% (80) P diff =0.608

Diabetics Endeavor IV

TVF Rate TVR Endeavor (n=224) Taxus (n=218) TLR MACE P =0.744 P =0.347 P =0.790 ENDEAVOR IV – 3yr FU Diabetics Efficacy Endpoints to 36 months P values were calculated by Fisher Exact Test Values are the event rates P = /22419/21835/22432/22434/21847/21829/22436/218

Non-Q Rate P =0.084 MI All Q-wave Endeavor (n=224) Taxus (n=218) CardiacDeath Cardiac Death and MI P values were calculated by Fisher Exact Test Values are the event rates ENDEAVOR IV – 3yr FU Diabetics Safety Endpoints to 36 months P =0.136 P =0.493 P = /2249/21813/2249/2181/2183/2247/2186/22416/218 P =0.029

ENDEAVOR IV – 3yr FU Diabetics CD/MI to 36 months Endeavor Taxus % 10% 4% 2% 0% Time after Initial Procedure (days) EndeavorTaxus 6% 8% 12% Cumulative Incidence of Cardiac Death or MI

Program Consistency Endeavor IV

Endeavor Randomized Clinical Trials CD/MI at Latest Available Follow-up Endeavor II to 5 years HR [95%CI] 1.28 [ ] P=0.265 Endeavor III to 4 years HR [95%CI] 4.19 [ ] P=0.024 NNH=24 Endeavor IV to 3 years HR [95%CI] 1.93 [ ] P=0.005 NNH=29 49/58238/5776/1104/30752/73427/734

Endeavor Randomized Clinical Trials TLR at Latest Available Follow-up Endeavor II to 5 years HR [95%CI] 2.19 [ ] P<0.001 NNT=11 Endeavor III to 4 years HR [95%CI] 0.81 [ ] P=0.832 Endeavor IV to 3 years HR [95%CI] 0.92 [ ] P= /58243/5777/11024/30744/73448/734

1yr 2yr 3yr 4yr 5yr Continued Access Single Arm (n = 296) 4yr ENDEAVOR II CA ENDEAVOR I Single Arm First-in-Man (n = 100) 5yr ENDEAVOR II ENDEAVOR III ENDEAVOR IV 1:1 RCT vs. Taxus ® (E = 773,T = 775) 3yr ENDEAVOR PK Single Arm (n = 99) 2yr ENDEAVOR Japan Premarket Safety and Efficacy Package Endeavor Clinical Program Pooled Safety and Efficacy Analyses 1:1 RCT vs. BMS (E = 598,D = 599) PK (n = 106) 5yr 3:1 RCT vs. Cypher® (E = 323,C = 113) 4yr Pharmacokinetic Study (n = 43) 3yr Included in Pooled Safety and Efficacy Analyses (N=2132)

Adherence to DAPT (%) Days DAPT 1 : E I, E II, E II CA, E III was ≥3 months Endeavor: E I, E II, EII CA, E III, E IV (n = 2132) DAPT 1 : E IV was ≥6 months 8% 24% 31% 39% 76% 96% 1. Protocol requirement DAPT usage based on case report forms. The optimal duration of dual antiplatelet therapy, specifically clopidogrel, is unknown and DES thrombosis may still occur despite continued therapy. Endeavor Clinical Program Pooled DAPT Compliance to 5 yrs

Cumulative Incidence of TLR % 0 20% 25% Endeavor % CI 0.09%5.43%6.23%6.75%6.84%6.95% Driver %13.16%14.23%14.78%15.91%16.49% Values are the KM estimates. P-values were calculated by Log Rank Test. 15% 10% 5% 1800 Time After Initial Procedure (days) Endeavor Driver Endeavor Pooled Efficacy Analysis Cumulative Incidence of TLR to 5 years 7.0% 16.5% Before 1 year Endeavor: 5.4% Driver: 13.2% Before 1 year Endeavor: 5.4% Driver: 13.2% After 1 year Endeavor: 1.6% Driver: 3.3% After 1 year Endeavor: 1.6% Driver: 3.3%

Cumulative Incidence of Cardiac Death or MI % 0 15% Endeavor % CI 1.41%2.83%3.42%3.77%4.42%5.42% Driver %4.54%5.75%6.62%6.98%8.42% Values are the KM estimates. P-values were calculated by Log Rank Test. 10% 5% 1800 Time After Initial Procedure (days) Endeavor Driver 5.4% 8.4% ENDEAVOR Pooled Safety Analysis Cumulative Incidence of CD/MI to 5 years Before 1 year Endeavor: 2.8% Driver: 4.5% Before 1 year Endeavor: 2.8% Driver: 4.5% After 1 year Endeavor: 2.7% Driver: 4.0% After 1 year Endeavor: 2.7% Driver: 4.0%

Endeavor Pooled Safety Analysis ARC Definite/Probable ST to 5 years Time After Initial Procedure (days) Cumulative Incidence of Def/Prob Thrombosis % 0 4% Endeavor % CI 0.05%0.62%0.71%0.71%0.80%0.80% Driver %1.35%1.35%1.52%1.52%1.71% Values are the KM estimates. P-values were calculated by Log Rank Test. 3% 2% % Endeavor Driver 0.8% 1.7% Before 1 year Endeavor: 0.6% Driver: 1.3% Before 1 year Endeavor: 0.6% Driver: 1.3% After 1 year (VLST) Endeavor: 0.2% Driver: 0.4% After 1 year (VLST) Endeavor: 0.2% Driver: 0.4%

Conclusions: Endeavor IV Late clinical FU (from 1-3 years) from the Endeavor IV RCT demonstrates: Late clinical FU (from 1-3 years) from the Endeavor IV RCT demonstrates: Endeavor has a significant safety advantage cw Taxus; overall, 48% reduction in cardiac death + MI (P=0.004) due to a 91% reduction in VLST from 1-3 yrs (11 vs. 1 events; P=0.004). The VLST frequency of Endeavor (0.1%) is similar to a bare metal stent. Endeavor has a significant safety advantage cw Taxus; overall, 48% reduction in cardiac death + MI (P=0.004) due to a 91% reduction in VLST from 1-3 yrs (11 vs. 1 events; P=0.004). The VLST frequency of Endeavor (0.1%) is similar to a bare metal stent. 3 years, reduced TVF, the 1 ry study endpoint, by 23%, from 15.9% to 12.3% (P=0.049) 3 years, reduced TVF, the 1 ry study endpoint, by 23%, from 15.9% to 12.3% (P=0.049) Overall 3 years was similar (Endeavor 6.5% vs. Taxus 6.0%) with a trend suggesting less late TLR (after 1 year) associated with Endeavor. Overall 3 years was similar (Endeavor 6.5% vs. Taxus 6.0%) with a trend suggesting less late TLR (after 1 year) associated with Endeavor.

Conclusions: Endeavor Program In More than 2100 patients studied with over 1000 patients now out to 5 years in pooled analysis: Low 7% TLR at 5 years in more than 1000 patients in ENDEAVOR Pooled AnalysisLow 7% TLR at 5 years in more than 1000 patients in ENDEAVOR Pooled Analysis Despite only 39% of patients on DAPT at 1 year in ENDEAVOR Pooled Analysis: 1Despite only 39% of patients on DAPT at 1 year in ENDEAVOR Pooled Analysis: 1 – Low 0.8% ST 2 to 5 years (BMS = 1.7%, p = 0.061) – Extremely low 0.2% VLST 2 after 1 year through 5 years – Significant reduction in CD/MI vs. BMS at 5 years (Endeavor 5.5% vs. BMS 8.4%, p = 0.009)