Washington Hospital Center, Division of Cardiology REWARDS Ron Waksman, Kimberly Kaneshige, Rebecca Torguson, Probal Roy, Zhenyi Xue, William Suddath, Lowell F. Satler, Kenneth M. Kent, Augusto D. Pichard Washington Hospital Center, Division of Cardiology Washington DC

Disclosures Advisory Board: Medtronic Boston Scientific, Abbott Vascular, Biotronik Speaker bureau: Medtronic Boston Scientific, Abbott Vascular, Biotronik Research grants: Medtronic Boston Scientific, Abbott Vascular, Biotronik, Shering Plaugh, GSK, Medicine company, Sanofi BMS This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 2 2

REWARDS Trial Aim The objective of this analysis was to compare the long-term outcomes up to 3 years (Efficacy and Safety) of patients receiving Cypher stents to those receiving Taxus stents with nonrestrictive use for all subset of patients and lesions.

Trial Structure REWARDS Investigator Sponsor Study Single Center with 11 cath labs 30 independent attending investigators Conducted under local IRB approval Clinical Follow-up at 1 month, 6 month, 1, 2, and 3 years via telephone or clinic office visit All events were adjudicated by independent physicians committee Data Management CRI, Washington Hospital Center

REWARDS Trial Design Successful PCI with DES & Complete 3 year follow up n = 3157 Cypher Stents n = 2192 pts Taxus Stents n = 965 pts Plavix Rx at least 3 M for Cypher and 6 M for Taxus Complete 3 year clinical follow-up all patients

REWARDS Definitions MACE: Composite of Death, Q wave Myocardial Infarction, Target Vessel Revascularization Stent Thrombosis: Angiographically documented stent thrombosis In hospital: prior to discharge Sub-acute: ≤ 30 days from stent implantation Late: > 30 days from stent implantation

Clinical Presentation REWARDS Clinical Presentation % Cypher n=2192 Taxus n=965 P value Stable Angina 34.4 26.5 <0.001 Unstable Angina 41.6 49.9 Acute MI 11.5 9.4 0.151 Cardiogenic Shock 3.0 2.0 0.150

Baseline Characteristics REWARDS Baseline Characteristics Clinical Characteristics (%) Cypher (n=2192) Taxus (n=965) p Value Age (yrs) 65.35 ± 11.43 66.21 ± 12.16 0.063 Male gender 62.6 67.8 0.005 Hypertension 81.3 79.7 0.293 Diabetes mellitus 35.5 36.2 0.730 Insulin treated diabetes 11.2 12.0 0.548 Hypercholesterolemia 86.7 83.0 0.007 Smokers at time of procedure 18.1 16.9 0.430 Previous myocardial infarction 32.0 34.6 0.151 Previous CABG 16.7 19.4 0.069 Previous PCI 25.4 28.0 0.120 History of chronic renal failure 11.8 14.4 0.041 Ejection fraction 0.48 ± 0.14 0.48 ± 0.13 0.858

In-Hospital Complications REWARDS In-Hospital Complications % Cypher pt=2192 les=4002 Taxus pt=965 les=1650 p Value Angiographic Success 97.6 98.1 0.275 Dissection 0.7 1.0 0.218 Abrupt Closure 0.3 0.084 No Reflow 0.5 0.8 0.162 Death 1.5 1.6 0.838 Myocardial infarction, Q-wave 0.4 0.259 Repeat TVR 2.8 1.8 0.088 Major bleeding 2.3 0.127 Stent thrombosis 1.000

1 Year Clinical Outcomes 2 Year Clinical Outcomes REWARDS Clinical Outcomes 1 Year Clinical Outcomes 2 Year Clinical Outcomes p=0.012 p=0.016

Unadjusted 3 Year Clinical Outcomes REWARDS Unadjusted 3 Year Clinical Outcomes Cypher n=2192 Taxus n=965 p Value MACE 27.7 28.7 0.58 Death 13.9 17.0 0.03 Myocardial infarction, Q-wave 0.7 1.7 0.02 Target vessel revascularization 16.7 14.4 0.12 Target lesion revascularization 13.3 10.6 0.05 ARC Definite Stent thrombosis 1.8 1.3 0.34

Adjusted 3 Year Clinical Outcomes REWARDS Adjusted 3 Year Clinical Outcomes P values 0.885 0.214 0.168 0.054 0.080

REWARDS K-M Curve for 3 Year MACE Logrank p=0.52 Overall

Independent Predictors of MACE within 3 years REWARDS Hazard Ratio 95% CI P value Male gender 0.9 0.8-1.0 0.121 Acute MI, presentation 1.3 1.1-1.6 0.005 Diabetes 1.5 1.3-1.7 <0.001 Hypercholesterolemia 1.0 0.8-1.2 0.897 Chronic Renal Insufficiency 2.4 2.0-2.8 Smoking 1.1 1.0-1.3 0.111 Age 1.0-1.0 Cypher Stent Usage 0.3-1.1 0.885

Cumulative Definite Stent Thrombosis – 3 Years REWARDS Cumulative Definite Stent Thrombosis – 3 Years Overall stent thrombosis for both stents at 3 years 1.7%

Cumulative Rates of Definite ST REWARDS Cumulative Rates of Definite ST %

Diabetic Sub-analyses REWARDS Diabetic Sub-analyses 1) All Diabetics 2) Insulin Dependent Diabetes Mellitus

Successful PCI with DES & Complete 3 year follow up REWARDS Diabetic Breakdown Successful PCI with DES & Complete 3 year follow up n = 3157 Cypher Stents n = 2192 pts Taxus Stents n = 965 pts All Diabetes Mellitus n = 770 All Diabetes Mellitus n = 348 IDDM n = 243 IDDM n = 115

REWARDS 36 Month MACE P=0.178 P=0.140 P=0.577

36 Month Clinical Outcomes REWARDS 36 Month Clinical Outcomes IDDM Overall DM P=0.245 Overall P=0.038 P=0.026 P=0.252 P=0.651 P=0.023

36 Month Cumulative Definite ST REWARDS 36 Month Cumulative Definite ST P=0.752 P=0.937 P=0.336 %

36 Month Cumulative Definite Late ST REWARDS 36 Month Cumulative Definite Late ST P=0.597 P=0.881 P=1.0 %

REWARDS Adjusted 3 Year MACE P Value 0.885 0.610 0.152

Independent Predictors of MACE within 3 years REWARDS Variable All DM IDDM HR [95%CI] P value Male gender 0.9 [0.7-1.1] 0.390 1.0 [0.7-1.4] 0.993 Acute MI, presentation 1.3 [0.9-1.7] 0.153 1.4 [0.8-2.4] 0.207 Hypercholesterolemia 1.1 [0.8-1.5] 0.535 1.0 [0.6-1.6] 0.969 Chronic Renal Insufficiency 2.5 [2.0-3.1] <0.001 2.3 [1.7-3.3] Smoking 1.0 [0.8-1.3] 0.849 1.2 [0.9-1.7] 0.235 Age 1.0 [1.0-1.0] 0.006 0.130 Cypher Stent Usage 0.9 [0.8-1.2] 0.610 0.8 [0.6-1.1] 0.152

Adjusted 3 Year Death & Q waveMI REWARDS Adjusted 3 Year Death & Q waveMI P Value 0.080 0.274 0.283

Independent Predictors of Death& Qwave MI within 3 years REWARDS Variable All DM IDDM HR [95%CI] P value Male gender 0.8 [0.6-1.1] 0.181 1.0 [0.7-1.5] 0.889 Acute MI, presentation 1.3 [0.8-1.9] 0.259 1.1 [0.6-2.3] 0.741 Hypercholesterolemia 0.985 1.0 [0.5-1.9] 0.982 Chronic Renal Insufficiency 3.8 [2.9-4.9] <0.001 4.0 [2.6-6.0] Smoking 1.2 [0.9-1.6] 0.192 1.4 [0.9-2.2] 0.094 Age 1.0 [1.0-1.0] 1.0 [1.0-1.1] Cypher Stent Usage 0.9 [0.7-1.1] 0.274 0.8 [0.5-1.2] 0.283

REWARDS Summary In an unselected patients population and lesions receiving DES there was no significant difference between patients receiving Cypher or Taxus stents with respect to MACE at 3 years. This similarity remained after adjustment for baseline characteristic differences. Death and Q wave MI were significantly higher in patients receiving Taxus than Cypher stents at 3 years. This significance, however, did not remain after adjustment.

REWARDS Conclusions The present study demonstrated that the use of Cypher and Taxus stents in unrestricted, contemporary practice had a comparable outcome in terms of low rates of revascularization and clinical events through 3 years. Cumulative stent thrombosis, (1.7% at three years for the entire cohort), remains a serious concern for both Cypher and Taxus Stent. These concerns are heightened for the insulin-dependent patients.