Five-Year Cumulative Rates of Clinical Events after Cypher™ Stent Implantation: Insights from a Patient-Level Pooled Analysis of Four Randomized Trials Comparing Sirolimus-Eluting Stents with Bare Metal Stents Adriano Caixeta, Roxana Mehran, Jeffrey W. Moses, George Dangas, Helen Parise, Ajay Kirtane, David R. Holmes, Charles O’Shaughnessy, Dennis Donohoe, Ronald Caputo, Dean J. Kereiakes, David O’ Williams, Martin B. Leon

Disclosure Statement of Financial Interest I, Adriano Caixeta DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

*Spaulding C, et al, N Engl J Med 2007;356:989-997. Background Sirolimus-eluting stents (SES) were approved for clinical use in 2003 to dramatically reduce the incidence of restenosis and rates of target lesion revascularization (TLR). Delayed arterial healing response after drug-eluting stent (DES) implantation has raised concerns about the long-term safety of DES. Although 4-year clinical outcomes in a pooled analysis of data from the four double-blind SES vs. bare metal stent (BMS) trials has been published recently*, 5-year clinical follow-up was scheduled by protocols in the four pivotal Cypher™ sirolimus-eluting stent (SES) and bare metal stent (BMS) randomized trial. *Spaulding C, et al, N Engl J Med 2007;356:989-997.

Purpose The aim of this study was to evaluate the 5-year safety and efficacy of SES compared with BMS. The primary safety endpoint was death or myocardial infarction (MI). The secondary safety endpoint was stent thrombosis adjudicated according to the Academic Research Consortium (ARC) definition. The primary efficacy endpoint was target vessel revascularization (TVR) up to 5 years. 3

Methods Patient-level Pooled Analysis RAVEL1 (N=238) SIRIUS2 (N=1058) E-SIRIUS3 (N=352) C-SIRIUS4 (N=100) August 2000 and April 2002 1,748 patients at 115 international centers De novo 15 to 32 mm long RD 2.5 to 3.5 mm Aspirin 81 to 325 mg Clopidogrel 75 mg 2-3 mo Cypher™ Sirolimus-eluting stent (N=878) BX Velocity Bare metal stent (N=870) 1Morice MC,et al, N Engl J Med 2002;346:1773-80. 2Moses JW, et al, N Engl J Med 2003;349:1315-23. 3Schofer J, et al, Lancet 2003;362:1093-9. 4Schampaert E, et al, J Am Coll Cardiol 2004;43:1110-5. 4

Results Baseline Characteristics I SES BMS p-value Age 61.85 +/- 11.12 61.91 +/- 10.67 0.91 Male gender, % 71.6% 71.5 % 0.96 Hypertension, % 63.8% 63.3 % 0.84 Hyperlipidemia, % 70.8% 71.8% 0.67 Current smoking, % 21.2% 24.5% 0.12 Diabetes mellitus, % 22.2% 26.8% 0.03 Prior MI, % 33.2% 35.7% 0.27 Prior PCI, % 22.9% 0.39 Prior CABG, % 7.5% 7.4% 0.93 Multivessel disease, % 38.6% 38.8% 0.92 Stable angina 23.1 % 25.0 % 0.37 Worsening angina 36.6% 33.3% 0.19 Rest angina 21.9% 21.8% 1.00

Results Procedure Characteristics SES BMS p-value Target lesion LAD, % 46.6% 46.7% 1.00 LCx, % 20.7% 20.8% RCA, % 29.0% 29.1% ACC/AHA lesion A, % 7.0% B1, % 33.9% 36.4% 0.29 B2, % 36.6% 38.1% 0.52 C, % 22.5% 18.5% 0.04 Vessel RD, mm 2.72 0.98 Total stent length, mm 22.87 22.45 0.31 Number of stents 1.42 1.39 0.38 IIbIIIa inhibitors, % 44.2% 43.4% 0.74

All Cause Mortality 8.9% P=0.57 8.2%

Cardiac Death P=0.55 4.4% 3.9%

Death and MI 15.1% P=0.36 13.6%

Definite/Probable Stent Thrombosis (ARC defined) 2.0% 2.1%

Target Lesion Revascularization P<0.01 24.7% 9.6%

Target Vessel Revascularization 30.1% P<0.01 15.2%

Results Annualized Hazard Ratio per 100 pt-years Year 1 Annual Hazard Rate per 100 pt-yrs Year 2 to 5 Annual Hazard Rate per 100 pt-yrs SES BMS P value p-value Death 1.3% (11) 0.8% (7) 0.3539 1.9% 0.7925 Cardiac Death 0.5% (4) 0.9916 1% 0.9% 0.5204 Non-Cardiac death 0.3% (3) 0.2101 1.1% 0.8003 MI 3.8% (33) 4.1% (36) 0.6966 0.7% 0.1081 QWMI 0.0% (0) N/A 0.3% 0.2% 0.4659 NQWMI 0.8% 0.5% 0.124 TLR 4.3% (37) 20.5% (177) <0.0001 1.3% 0.1268 TVR 9.5% (82) 25.3% (218) 2.4% 2.1% 0.2455 Remote TVR (non-TLR) 2.6% (23) 5.0% (43) 0.0117 1.4% 0.6753 Definite ST 0.9933 0.1% 0.1659 Definite + Probable ST 0.7% (6) 0.2192 0.4% 0.2257 Any (Definite + Probable + Possible) ST 1.6% (14) 0.1222 0.2769 Death/MI 4.9% (43) 4.6% (40) 0.7658 2.8% 0.3162 Death/Q-MI 2.2% 2% 0.6681 Death/MI/TVR 13.0% (114) 27.9% (242) 4.5% 4.2% 0.4038

Diabetic Subgroup: Death 16.1% 9.9%

Diabetic Subgroup: Death or MI 20.9% 17.4%

Conclusions In a patient-level pooled analysis of the four SES and BMS randomized trials, no significant differences in the rates of death, MI, death/MI were observed at 5 years. In pts with diabetes, however, treatment with SES was associated with a statistically higher incidence of death at 5 years. No significant differences in the rates of any ARC-defined stent thrombosis were observed between SES and BMS at 5 years. A significant difference in TVR rate was observed in favor of pts treated with SES at 5 years. 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) 16