Ron Waksman Kimberly Kaneshige Rebecca Torguson Probal Roy

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 n Advisory Board: Medtronic Boston Scientific, Abbott Vascular, Biotronik n Speaker bureau: Medtronic Boston Scientific, Abbott Vascular, Biotronik n Research grants: Medtronic Boston Scientific, Abbott Vascular, Biotronik, Shering Plaugh, GSK, Medicine company, Sanofi BMS

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 n n n n 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

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

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

Clinical Presentation Cypher n=2192 Taxus n=965 P value Stable Angina 34. 4 26. 5 <0. 001 Unstable Angina 41. 6 49. 9 <0. 001 Acute MI 11. 5 9. 4 0. 151 Cardiogenic Shock 3. 0 2. 0 0. 150 %

Baseline Characteristics Clinical Characteristics (%) Cypher (n=2192) Taxus (n=965) p Value 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 0. 48 ± 0. 14 0. 48 ± 0. 13 0. 858 Age (yrs) Ejection fraction

In-Hospital Complications % Angiographic Success Dissection Abrupt Closure No Reflow Death Myocardial infarction, Q-wave Repeat TVR Major bleeding Stent thrombosis Cypher Taxus pt=2192 pt=965 p Value les=4002 les=1650 97. 6 98. 1 0. 275 0. 7 0. 3 0. 5 1. 5 0. 4 2. 8 1. 5 0. 3 1. 0 0. 7 0. 8 1. 6 0. 7 1. 8 2. 3 0. 218 0. 084 0. 162 0. 838 0. 259 0. 088 0. 127 1. 000

Clinical Outcomes 1 Year Clinical Outcomes 2 Year Clinical Outcomes p=0. 012 p=0. 016

Unadjusted 3 Year Clinical Outcomes Cypher n=2192 Taxus n=965 p Value 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 MACE

Adjusted 3 Year Clinical Outcomes P values 0. 885 0. 214 0. 168 0. 054 0. 080

K-M Curve for 3 Year MACE Logrank p=0. 52

Independent Predictors of MACE within 3 years Hazard 95% CI P value Ratio 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 <0. 001 Smoking 1. 1 1. 0 -1. 3 0. 111 Age 1. 0 -1. 0 <0. 001 Cypher Stent Usage 1. 0 0. 3 -1. 1 0. 885

Cumulative Definite Stent Thrombosis – 3 Years Overall stent thrombosis for both stents at 3 years 1. 7%

Cumulative Rates of Definite ST %

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

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

36 Month MACE P=0. 178 P=0. 140 P=0. 577

36 Month Clinical Outcomes Overall DM IDDM P=0. 245 P=0. 038 P=0. 026 P=0. 023 P=0. 252 P=0. 651

36 Month Cumulative Definite ST P=0. 752 P=0. 937 P=0. 336 %

36 Month Cumulative Definite Late ST P=0. 597 P=0. 881 % P=1. 0

Adjusted 3 Year MACE P Value 0. 885 0. 610 0. 152

Independent Predictors of MACE within 3 years All DM IDDM Variable 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] <0. 001 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 1. 0 [1. 0 -1. 0] 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 wave. MI P Value 0. 080 0. 274 0. 283

Independent Predictors of Death& Qwave MI within 3 years All DM IDDM Variable 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 1. 0 [0. 7 -1. 5] 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] <0. 001 Smoking 1. 2 [0. 9 -1. 6] 0. 192 1. 4 [0. 9 -2. 2] 0. 094 Age 1. 0 [1. 0 -1. 0] <0. 001 1. 0 [1. 0 -1. 1] <0. 001 Cypher Stent Usage 0. 9 [0. 7 -1. 1] 0. 274 0. 8 [0. 5 -1. 2] 0. 283

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.

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.