1. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 RAVEL A RAndomised, double-blind study with the Sirolimus-eluting Bx VElocity ™ balloon expandable stent in the treatment of patients with de novo native coronary artery Lesions Authors: J.E. Sousa, M.C. Morice, P.W. Serruys, J. Fajadet, M. Perin, E. Ban Hayashi, A. Colombo, G. Schuler, P. Barragan, C. Bode EuroPCR - 2005 Paris, May 24 th - 27 th, 2005

2. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Name of the speaker: J. Eduardo Sousa, MD, PhD, FACC  I have the following potential conflicts of interest to report:  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 Potential conflicts of interest EuroPCR 2005 X

3. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 History of the RAVEL Study The first randomized study on a drug-eluting stent: From 1999 – 2001 in 19 centers in Europe and Latin America Primary Investigator: Dr. Marie-Claude Morice Prim. Objective: safety and effectiveness of Cypher stent Prim. Endpoint: In-stent late loss at 6 month follow-up Sec. Endpoint: Binary restenosis, %DS, MLD in-stent/segment, MACE, TLR, TVR, health economics data 6-month FU: Late loss: -0.01mm vs 0.80mm (bare) Binary Restenosis: 0.0% vs 26% Total TLR: 0.0% vs 22.9% MACE: 3.3% vs 27.1% Stent thrombosis:0.0% vs 0.0% Clinical follow-up at 1, 2, 3, 4, and 5 years

4. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Inclusion and Exclusion Criteria Inclusion Criteria: Patients with angina pectoris (stable, unstable, silent ischemia) Single de novo lesions Target lesion stenosis is >50% - <100% (  TIMI 1; no CTOs) Native vessel: diameter  2.5 -  3.5mm Lesion to be covered by a single stent of 18mm length Exclusion Criteria: Unprotected left main, bifurcated, ostial, or heavily calcified lesions AMI < 72 h, Thrombus in lesion EF < 30% Direct stenting Pretreatment different from POBA Anti-Platelet Therapy (Ticlopidin, Clopidogrel) for 2 months

5. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Baseline - Demographics Male 70 81 Mean age (years) 62 60 Previous MI 38 34 Previous revascularization 21 19 Diabetes mellitus 16 21 Hypercholesterolemia (treated) 38 43 Hypertension (treated) 62 61 Current smoker 27 33 Sirolimus (%) Control (%) N=120 N=118 Figure in Blue indicates statistical difference (95% CI)

6. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Baseline - Lesion Characteristics Location of lesion LAD 49 51 RCA 27 27 LCX 24 22 Lesion classification Type A 8 4 Type B1 39 35 Type B2 54 61 Type C 0 0 Sirolimus (%) Control (%) N=120 N=118 No statistical differences (95% CI)

7. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Sirolimus Control P-value Sirolimus Control P-value N=118* ( %) N=115* ( %) N=118* ( %) N=115* ( %) Death 13 (11.0) 7 (6.1) cardiac 3 (2.5) 5 (4.3) non-cardiac 10 (8.5) 2 (1.7) MIQ-wave 3 (2.5) 1 (0.9) Non Q-wave 3 (2.5) 3 (2.6) TLR CABG 3 (2.5) 2 (1.7) TLR re-PCI 4 (3.4) 27 (23.5) TLR total 7 (5.9) 29 (25.2) MACE-free 92 (78.0) 75 (65.2) 0.04 * 5 patients excluded from analysis as no Informed Consent was obtained for 2-5 year protocol extension MACE up to 4 Years (hierarchical ranking) including all TLRs (clinically and non-clinically driven)

8. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Deaths in Sirolimus Group No. Patient:Diagnosis: CEC Adjudication: #1010:Lung cancer non-cardiac #1019:Pneumonia non-cardiac #1052:Gastrointest. cancer non-cardiac #1063:Heart failure cardiac #1099:Stroke non-cardiac #1123:Pneumonia non-cardiac #1146:Pulmonary embolism non-cardiac #1168:Heart failure cardiac #1198:Cerebr. hemorrhagenon-cardiac #1204:Subarach. hemorrhage non-cardiac #1264:Pancreatic cancer non-cardiac #1299:Heart failure cardiac #1306:Prostate cancer non-cardiac

9. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 MACE (including Death, MI, all TLRs) Patients without event (%) Time (Days) 0 365 730 1095 1460 100 95 90 85 80 75 70 65 60 77.5% 65.0% Sirolimus Bare metal stent P = 0.04 (Fisher‘s exact test) P = 0.01 (Log-rank test)

10. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 MACE (including clinically-driven TLRs only) 95 90 80 75 70 65 60 Patients without event (%) Time (Days) 100 95 90 85 80 75 70 65 60 0 365 730 1095 1460 78.3% 75.5% Sirolimus Bare metal stent P = 0.39 (Log-rank test) P = 0.64 (Fisher‘s exact test)

11. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 TLR: all (clinically and non-clinically driven) Patients without event (%) Time (Days) 0 365 730 1095 1460 100 95 90 85 80 75 70 65 60 91.8% 73.4% Sirolimus Bare metal stent P = <0.001 (Log-rank test) P = <0.001 (Fisher‘s exact test)

12. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 TVF (including all TVRs) Patients without event (%) Time (Days) 0 365 730 1095 1460 100 95 90 85 80 75 70 65 60 84.6% 65.0% Bare metal stent Sirolimus P = <0.001 (Log-rank test) P = <0.001 (Fisher‘s exact test)

13. RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Summary At 4 years, there continues to be a significant difference in the protocol defined secondary endpoint of MACE (defined as death, MI, and total TLR). Statistical significance in MACE (defined as death, MI, and clinically- driven TLR) is not maintained. However, this is driven by a non significant higher rate of non-cardiac deaths in the sirolimus group (10 vs 3 cases). This benefit does not occur at the expense of stent-related side effects, with stent thrombosis and late stent thrombosis rates remaining at zero. At 4 years, the sirolimus-eluting stent continues to demonstate durability of clinical benefit with a significant reduction total and clinicaly-driven TLR and TVF