Maintenance of Long-Term Clinical Benefit with Sirolimus-Eluting Stents in Patients with ST-Segment Elevation Myocardial Infarction: Three-year results of the SESAMI Trial Musto C, Fiorilli R, De Felice F, Nazzaro MS, Cifarelli A, Violini R Interventional Cardiology Department, San Camillo Hospital, Rome

Presenter Disclosure Information Name: Carmine Musto Maintenance of Long-Term Clinical Benefit with Sirolimus-Eluting Stents in Patients with ST-Segment Elevation Myocardial Infarction: Three-year results of the SESAMI Trial Presenter Disclosure Information Name: Carmine Musto Nothing to Disclose

INTRODUCTION Primary PCI has become the treatment of choice in patients presenting with STEMI The incidence of BMS re-stenosis in the STEMI patients remains high leading to rehospitalization and increased costs DES implantation reduces neo-intimal proliferation with better short- and long-term clinical and angiographic results compared to BMS

DES in AMI: 1-year TVR % p=0.006 p<0.001 p< 0.015 p= 0.23 p<0.01 20 13.1 13.4 13.2 7.8 7 5.3 5.6 5 5.1

DES in AMI:1-year stent thrombosis Kastrati A et al. Eur Heart J 2007;28:2706-13

INTRODUCTION The use of DES in AMI remains controversial Randomized data on safety and clinical benefit of DES have usually been limited to ≤ 2 years Data from registries have provided mixed results with respect to the long-term safety of DES in the setting of AMI Long-term follow-up data from randomized trials on the use of DES in AMI are mandatory

AIM To define whether the favourable effect on clinical outcome, observed in the SESAMI trial (Sirolimus Eluting-Stent in Acute Myocardial Infarction) persisted at 3 years’ follow-up

SESAMI TRIAL PROTOCOL 423 Elegible patients with STEMI Patients excluded: 103 LM disease: 3 Graft disease: 15 Cardiogenic shock: 32 No consent: 19 Primary or Rescue Angioplasty Randomized Patients:320 Allocated to SES: 160 Allocated to BMS: 160 86 pts, 12 months angiographic f-u 80 pts, 12 months angiographic f-u Menichelli M et al. J Am Coll Cardiol 2007;49:1924-30

METHODS Inclusion criteria: Exclusion criteria: > 18 years Symptoms of acute MI for ≥ 30 min but ≤ 12 h ≥ 1 mm ST-segment elevation in at least 2 contiguous leads or LBBB Exclusion criteria: Cardiogenic shock History of bleeding diathesis, leukopenia, thrombocytopenia, severe renal or hepatic dysfunction Non-cardiac disorder associated with a life expectancy of <1 year LM or graft disease Involved in another study or unable to give informed consent

METHODS Study end-points Primary end-point Secondary end-points 3-year MACE 3-year TLR 3-year TVR 3-year TVF MACE: composite of cardiac and non-cardiac death, Q-wave and non-Q-wave MI, TLR TLR: repeated PCI or CABG of the target lesion driven by symptoms of ischemia, positive stress test due to the target vessel or in-stent restenosis >70% TVR: repeated revascularization within the treated vessel TVF: combination of TVR, recurrent MI or target vessel-related death

RESULTS Baseline characteristics of SES and BMS groups N. patients 160 160 Age, years (mean, range) 63 (54-70) 62 (52-72) 0.81 Male gender, n. (%) 128 (80) 128 (80) Diabetes mellitus, n. (%) 28 (17.5) 37 (23.7) 0.13 Hypertension, n. (%) 87 (54.3) 98 (58.7) 0.20 Hyperlipidemia, n. (%) 123 (62.5) 105 (65%) 0.12 Smoker, n. (%) 91 (56.8) 83 (51.7) 0.1 Prior myocardial infarction, n. (%) 9 (5.6) 20 (12.5) 0.047 Prior PCI, n. (%) 15 (9.4) 17 (10.6%) 0.38 Time from symptom onset to PCI (h) (mean, range) 4 (3-7) 4 (3-6) 0.64 Rescue PCI, n. (%) 28 (17.5) 29 (18.2) 0.54 TIMI risk score (mean) 3.7 3.1 0.10 *DAT (days±SD) † 375±12 369±35 NS SES BMS p * Dual anti-platelet therapy

RESULTS Procedural characteristics of SES and BMS groups SES group BMS group p Abciximab therapy (%) 124 (77.5) 118 (74%) NS Infarct-related vessel (%): LAD 46.6 52.5 0.29 Cx 13.3 12.7 0.54 RCA 40.1 34.8 0.46 TIMI III pre-procedural (%) 17.2 19.3 0.58 TIMI III post-procedural (%) 93.8 96.2 0.35 Stent length (mm±SD) 19.4±4.8 16.9±4.1 0.001 Stent diameter (mm±SD) 3.02±0.28 3.14±0.034 0.001

1-year angiographic follow-up p<0.05 p<0.05 % 21.3 17.2 9.3 5.6 Menichelli M et al. J Am Coll Cardiol 2007;49:1924-30

CLINICAL OUTCOME: 1-year follow-up % p<0.005 p<0.02 p<0.015 p<0.007 18.7 16.8 13.1 11.2 8.7 6.8 5 4.3 Menichelli M et al. J Am Coll Cardiol 2007;49:1924-30

CLINICAL OUTCOME: 3-year follow-up % 21 20.5 16 12.7 13.5 11.5 p=NS 8.3 7 5 3.2 2.5 2.5 1.9 1.3 Complete SES group F-U: 98% Complete BMS group F-U: 97.5%

Actuarial rate of survival free from MACE 1.00 87% p<0.05 79% 0.75 MACE-free survival (%) 0.50 0.25 0.00 6 12 18 24 30 36 Months BMS SES

Actuarial rate of survival free from TLR 1.00 93% p<0.05 86.5% 0.75 TLR-free survival (%) 0.50 0.25 0.00 6 12 18 24 30 36 Months BMS SES 17

Actuarial rate of survival free from TVF 1.00 89.5% p<0.05 79.5% 0.75 TVF Free Survival (%) 0.50 0.25 0.00 6 12 18 24 30 36 Months BMS SES 18

Stent Thrombosis p=NS p=NS 1.9 % 1.3 0.8 0.7

Clinical events during 12 to 36 months’ follow-up SES group BMS group p N. patients 144 127 Death, n. (%) (95% C.I.) 2 (1.4) (0.1-4) 1 (0.8) (0.01-4.3) NS Re-infarction, n. (%) (95% C.I.) 1 (0.7) (0.01-3) 1 (0.8) (0.01-4.3) NS Stent thrombosis n. (%) (95% C.I.): Definite 1 (0.7) (0.01-3) 1 (0.8) (0.01-4.3) NS Probable/possible 0 0 NS MACE, n. (%) (95% C.I.) 7 (4.8) (1.9-9) 5 (3.9) (1.2-8.9) NS TLR, n. (%) (95% C.I.) 4 (2.7) (0.7-6.9) 3 (2.3) (0.4-6.7) NS TVR, n. (%) (95% C.I.) 6 (4.1) (1.5-8.8) 7 (5.5) (2.2-11) NS TVF, n. (%) (95% C.I.) 7 (4.8) (1.9-9.7) 8 (6.3) (2.7-12) NS Death/ re-MI, n. (%) (95% C.I.) 3 (2) (0.4-5.9) 2 (1.5) (0.1-5.5) NS

LIMITS Small, single center study designed to compare the efficacy of the SES vs BMS in the STEMI setting Not powered to demonstrate significant differences in terms of death, re-MI or ST

Conclusions The SESAMI trial demonstrated that: The cumulative incidence of MACE, TLR, TVR and TVF remains lower in the SES group compared to the BMS group at 3-year clinical follow-up The better results in the SES group are due primarily to the different rate of TLR No significant differences in terms of death, re-MI or ST were found with 1-year dual anti-platelet therapy No increased risk of adverse events was found following withdrawal of dual anti-platelet therapy