DIABETES 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) 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 Long-term follow-up of the DIABETES I (DIABETes and sirolimus Eluting Stent) trial:

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

DIABETES trial 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 IVUS at 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.

DIABETES trial 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.

DIABETES trial 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.

DIABETES trial 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.

DIABETES trial 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. Definition:

DIABETES trial Flow Chart: 160 Pts Randomization Inclusion Criteria Informed Consent Inclusion Criteria Informed Consent Rx Centralized Sub Rx: type of DM Rx Centralized Sub Rx: type of DM 80 pts SES80 pts BMS 110 lesions 9 Mo Angio FU (92%) 1-y clinical FU (100%) 2-y clinical U (97.5%) 111 lesions 2 cardiac deaths 8 missing 2 cardiac deaths 8 missing 1 cardiac death 2 non- cardiac death 2 missing 1 cardiac death 2 non- cardiac death 2 missing 9 Mo Angio FU (91%) 1-y clinical FU (100%) 2-y clinical U (100%) Abciximab + ASA mg/day + Clopidogrel 75 mg/day (at least 1 year)

DIABETES trial QCA and IVUS analysis

DIABETES trial Baseline Baseline Characteristics Characteristics SES n=80 BMS n=80 Age, y66 ± ± 9.6 Female, %39 ID Diabetes, %3334 NID Diabetes, %6766 Hypertension, %66 Current smoker, n %4550 Dyslipidemia, n %61 Previous MI, n %3143 Previous revascularization %2018 Ejection Fraction, %67 ±1363 ±14 HbA1c, %7.4 ± ±1.4 LDL-cholesterol, mg/dl104 ±31104 ±28 Creatine clearance, ml/min71 ±2375 ±30 p= NS DIABETES

DIABETES trial p= NS SES n=111 BMS n=110 Treated artery, % LAD/LCX/RCA39/21/4044/23/33 Lesion length*, mm14.5± ±7.6 Reference diam, mm2.3±0.5 Total occl, %1314 Multivessel stent, %2324 N. stenosis / patient1.4±0.61.4±0.5 N. stent / patient1.6±0.81.7±0.9 Stent length, mm22±1023±13 IIb/IIIa inhibitors, %6454 Angiographic/Procedural characteristics *excluding CTO

DIABETES trial 2-year results

DIABETES trial 2-years Results SES (n=80) BMS (n=80) p value Cardiac death, n (%)2 (2.6)3 (3.8)1 MI, n (%) Non-Q wave Q-wave 3 (3.8) 1 (1.3) 2 (2.6) 7 (8.8) 6 (7.5) 1 (1.3) TLR, n (%) PCI Bypass 6 (7.7) 0 (0) 28 (35.0) 27 (33.8) 1 (1.3) < MACE, n (%)10 (12.8)33 (41.3)<0.001

DIABETES trial % FREEDOM FROM TLR Event-free survival (%) Time (days) Long rank test< Sirolimus stent Bare metal stent 92% 65%

DIABETES trial CLINICAL ATHEROSCLEROSIS PROGRESSION at 2-year % 7.7% 10.0% SESBMS

DIABETES trial Time (days) Sirolimus stent Bare metal stent % FREEDOM FROM ANY REVASCULARIZATION Time after initial procedure Test Long rank =0,0008 Event-free survival (%) 85% 61%

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

DIABETES trial Stent thromboses after clopidogrel withdrawal (> 1 year) 0% 3 (3.8%) BMSSES

DIABETES trial Conclusions (I): DIABETES trial demonstrated that the significant reduction in clinical restenosis 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. DIABETES trial demonstrated that the significant reduction in clinical restenosis 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.