No conflict of interest

1. Long-term follow-up of theDIABETESI (DIABETes and sirolimus Eluting Stent) trial: P Jiménez-Quevedo, M Sabaté, DJ Angiolillo, JA Gómez-Hospital, R Hernández-Antolín, J Goicolea, F Alfonso, C Bañuelos, J Escaned, R Moreno, F Fernández-Avilés, C Macaya (On behalf of the DIABETES Investigators) No conflict of interest

2. DIABETES (DIABETes and sirolimus Eluting Stent trial) . . . Multicenter, Prospective, Randomized. 4 2 . 3 1 1 - Hospital San Carlos Madrid. 2 - Hospital de Bellvitge Barcelona. 3 - Hospital Clínico Valladolid 4 - Hospital do Meixoeiro Vigo

3. DIABETES TRIAL design PRIMARY ENDPOINT • Late lumen loss (in-stent and in-segment) as assessed by QCA at 9-month angiographic follow-up. SECONDARY ENDPOINTS • Other QCA parameters (restenosis, MLD) at FU. • Mean neointimal hyperplasia and % volume obstruction by IVUSat 9-month follow-up. • MACE (Cardiac death, MI and TLR) at 30 d, 9,12, 13 and 24 months. • Development of complications: aneurysm formation, late thrombosis, edge effect, late stent malapposition.

4. Inclusion criteria: • Diabetic patient (non-insulin dependent or insulin dependent) according to WHO 1999 Report. • Coronary lesions in native coronary arteries and symptoms or objective evidence of ischemia. • Lesion favourable for PTCA + stent implantation. • Informed consent.

5. Exclusion criteria: • Diabetic patient without pharmacological treatment (on diet). • Stenoses located in true bifurcations, SVG, LIMA or unprotected left main. • In-stent restenosis. • Chronic renal or hepatic insufficiency. • Previous brachytherapy or DES implantation. • Recent AMI (<72h) with CPK (x 2). • Malignancy.

6. Objectives: To present the Long-term clinical follow-up of patients included in the DIABETES trial: • Need for repeated TLR. • Need for non-TLR (atherosclerosis progression). • Safety after clopidogrel withdrawal at 1-year.

7. Definition: • Clinical atherosclerosis progression: • the need for revascularization secondary to development of new significant coronary stenoses, not present in previous angiograms, accompanied by symptoms or evidence of ischemia.

8. Flow Chart: 160 Pts Randomization Inclusion Criteria Informed Consent Rx Centralized Sub Rx: type of DM 80 pts SES 80 pts BMS 111 lesions 110 lesions Abciximab + ASA 100-300 mg/day + Clopidogrel 75 mg/day (at least 1 year) 1 cardiac death 2 non- cardiac death 2 missing 2 cardiac deaths 8 missing 9 Mo Angio FU (92%) 1-y clinical FU (100%) 2-y clinical U (97.5%) 9 Mo Angio FU (91%) 1-y clinical FU (100%) 2-y clinical U (100%)

9. QCA and IVUS analysis

10. DIABETES p= NS

11. Angiographic/Procedural characteristics p= NS *excluding CTO

12. 2-year results

14. Sirolimus stent Bare metal stent 0 200 400 600 800 % FREEDOM FROM TLR 100 92% 80 65% 60 Event-free survival (%) 40 Long rank test<0.0001 20 0 Time (days)

15. SES BMS CLINICAL ATHEROSCLEROSIS PROGRESSION at 2-year % 10.0% 7.7%

16. 100 80 60 40 Sirolimus stent Bare metal stent 20 0 0 200 400 600 800 % FREEDOM FROM ANY REVASCULARIZATION 85% 61% Event-free survival (%) Test Long rank =0,0008 Time (days) Time after initial procedure

17. Sirolimus Stent Bare metal Stent 1(1.3%) 1(1.3%) 0% 0% Stent thromboses during dual antiplatelet treatment (<1-y) <30 days 30-365 days

18. 3 (3.8%) 0% BMS SES Stent thromboses after clopidogrel withdrawal (> 1 year)

19. Conclusions (I): • DIABETES trial demonstrated that the significant reduction in clinicalrestenosis and major cardiac events observed in the Sirolimus group persisted up to 2 years. • This benefitial effect of sirolimus stent implantation may be tarnished by long term incidence of late stent thrombosis after clopidogrel withdrawal.