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 Paris, May 24 th - 27 th, 2005

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

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

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   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

RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Baseline - Demographics Male Mean age (years) Previous MI Previous revascularization Diabetes mellitus Hypercholesterolemia (treated) Hypertension (treated) Current smoker Sirolimus (%) Control (%) N=120 N=118 Figure in Blue indicates statistical difference (95% CI)

RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 Baseline - Lesion Characteristics Location of lesion LAD RCA LCX Lesion classification Type A 8 4 Type B Type B Type C 0 0 Sirolimus (%) Control (%) N=120 N=118 No statistical differences (95% CI)

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)

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

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) % 65.0% Sirolimus Bare metal stent P = 0.04 (Fisher‘s exact test) P = 0.01 (Log-rank test)

RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 MACE (including clinically-driven TLRs only) Patients without event (%) Time (Days) % 75.5% Sirolimus Bare metal stent P = 0.39 (Log-rank test) P = 0.64 (Fisher‘s exact test)

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) % 73.4% Sirolimus Bare metal stent P = <0.001 (Log-rank test) P = <0.001 (Fisher‘s exact test)

RAVEL 4 YEAR FOLLOW-UP - Cordis Cardiology / Cardialysis – Euro-PCR – Sousa – 24 May 2005 TVF (including all TVRs) Patients without event (%) Time (Days) % 65.0% Bare metal stent Sirolimus P = <0.001 (Log-rank test) P = <0.001 (Fisher‘s exact test)

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