The SOS Stenting Of Saphenous vein grafts Randomized

The SOS (Stenting Of Saphenous vein grafts) Randomized, Controlled Trial of a Paclitaxel-Eluting Stent Vs. a Similar Bare Metal Stent in Saphenous Vein Graft Lesions Emmanouil S. Brilakis, MD, Ph. D Director, Cardiac Catheterization Laboratory VA North Texas Healthcare System On behalf of the SOS investigators

Disclosure Statement of Financial Interest I, Emmanouil Brilakis 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.

Funding • Veteran Affairs, VISN-17 • Clark R. Gregg fund, Harris Methodist Foundation, Fort Worth, Texas

SOS design • DESIGN: Prospective, randomized, multi-center trial comparing the Taxus™ paclitaxel-eluting stent (PES) with a similar Express 2™ bare metal stent (BMS) in saphenous vein graft (SVG) lesions • OBJECTIVE: To compare the 12 -month angiographic and 24 -month clinical outcomes between PES and BMS in SVG lesions • PRINCIPAL INVESTIGATOR: Emmanouil S. Brilakis, MD, Ph. D. VA North Texas Healthcare System, Dallas, Texas

SOS: sample size determination • 31 patients needed per group to have 80% power (2 -sided alpha 0. 05) to detect a 66% reduction in binary angiographic restenosis assuming 50% restenosis in BMS group and 1 lesion treated per pt • Target enrollment: 40 patients per group to account for losses during follow-up

SOS: Patient flow 80 patients (112 lesions) enrolled between 2005 and 2007 in 5 clinical sites in USA and Europe BMS 39 pts 55 lesions PES 41 pts 57 lesions Died: 4 pts Emergent CABG: 1 pt Declined: 3 pts Died: 1 pt Declined: 5 pts Angiographic follow-up at 12 months 33 pts 47 lesions Angiographic follow-up at 12 months 33 pts 43 lesions Died: 1 pt Clinical follow-up at 24 months median follow-up: 18 months

SOS trial centers Iowa City VAMC • James Rossen, MD Michael E. De. Bakey VAMC • Biswajit Kar, MD Little Rock VAMC • Joe K. Bissett, MD • Rajesh Sachdeva, MD VA North Texas HCS Coordinating Ctr • Emmanouil Brilakis, MD, Ph. D • Subhash Banerjee, MD • Christopher Lichtenwalter, MD • James de Lemos, MD • Owen Obel, MD • Michele Roesle, RN Onassis Cardiac Surgery Ctr Athens, Greece • Vassilios Voudris, MD • Panagiotis Karyofillis, MD Collaborators: Peter Berger, MD Panayotis Fasseas, MD

Baseline characteristics I Age (yrs) Men (%) White (%) Diabetes (%) Current smoker (%) Hypertension (%) Hyperlipidemia (%) BMS n = 39 67 ± 9 100 90 44 23 95 95 PES n = 41 66 ± 9 100 98 44 29 93 98 P Value 0. 71 1. 0 0. 19 0. 98 0. 53 0. 69 0. 53

Baseline characteristics II Years since CABG Presentation - Stable angina (%) - ACS (%) BMI (kg/m 2) Prior MI (%) Normal ejection fraction (%) BMS n = 39 12 ± 6 33 57 29 ± 4 59 61 PES P Value n = 41 11 ± 6 0. 84 0. 53 29 63 30 ± 5 0. 32 56 0. 79 51 0. 53

Procedural description I BMS n = 39 SVG recipient vessel - LAD/diagonal (%) - Circumflex/OM (%) - RCA/PDA (%) Lesion location - Aortic anastomosis (%) PES P Value n = 41 0. 37 30 27 30 40 44 29 0. 80 27 26 - Body (%) 66 67 - Distal anastomosis (%) 7 7

Procedural description II BMS n = 39 PES n = 41 P Valu e Number of SVGs treated 1. 15 ± 0. 37 1. 12 ± 0. 33 0. 68 Number of lesions treated Number of stents/lesion 1. 41 ± 0. 64 1. 39 ± 0. 70 0. 89 1. 13 ± 0. 34 1. 09 ± 0. 29 0. 50 Predilatation (%) Embolic protection (%) Max balloon diameter, mm 29 56 33 51 0. 63 0. 56 3. 20 ± 0. 48 3. 30 ± 0. 52 0. 40 Max inflation pressure, atm 17 ± 3 0. 37 Stent length, mm 18 ± 6 0. 90

Procedural description III Heparin (%) GP IIb/IIIa inhibitors (%) Contrast, m. L Fluoroscopy, min Post PCI MI (%) Procedural success (%) BMS n = 39 PES n = 41 P Value 79 83 0. 69 13 10 0. 66 257 ± 105 262 ± 98 0. 84 20 ± 9 21 ± 11 0. 64 7 6 0. 87 97 95 0. 59

Late Loss BMS (47 lesions), PES (43 lesions) ± 1. 03 ± 0. 98 mm ± 0. 57 Diff (95% CI) -0. 87 (-0. 51, -1. 22) P<0. 0001 ± 0. 54 Diff (95% CI) -0. 81 (-0. 48, -1. 46) P<0. 0001

Binary angiographic restenosis Primary study endpoint % relative risk: 0. 18 95% CI: 0. 07, 0. 48 p < 0. 0001

Cumulative frequency distribution curves 100 Before intervention 75 % BMS PES 50 25 0 0 1 2 3 Minimum lumen diameter (mm) 4

Cumulative frequency distribution curves 100 Before intervention 75 % BMS PES 50 After intervention (in-stent minimum lumen diameter) 25 0 0 1 2 3 Minimum lumen diameter (mm) 4

Cumulative frequency distribution curves 100 75 BMS PES Follow-up BMS % 50 After intervention 25 Follow-up PES 0 0 1 2 3 4 In-stent minimum lumen diameter (mm)

Clinical outcomes median follow-up: 1. 5 years

Clinical outcomes median follow-up: 1. 5 years BMS n = 39 Death (%) 5 PES P Value n = 41 12 0. 27

Clinical outcomes median follow-up: 1. 5 years BMS n = 39 Death (%) Myocardial infarction (%) 5 31 PES P Value n = 41 12 15 0. 27 0. 10

Clinical outcomes median follow-up: 1. 5 years BMS n = 39 PES P Value n = 41 Death (%) Myocardial infarction (%) 5 31 12 15 0. 27 0. 10 TLR (%) TVR (%) Any revascularization (%) 28 31 41 5 15 20 0. 003 0. 08 0. 02

Clinical outcomes median follow-up: 1. 5 years BMS n = 39 PES P Value n = 41 Death (%) Myocardial infarction (%) 5 31 12 15 0. 27 0. 10 TLR (%) TVR (%) Any revascularization (%) Target vessel failure (%) 28 31 41 5 15 20 0. 003 0. 08 0. 02 46 22 0. 03 Overall MACE (%) 49 37 0. 20

Clinical outcomes median follow-up: 1. 5 years BMS n = 39 PES P Value n = 41 Death (%) Myocardial infarction (%) TLR (%) TVR (%) Any revascularization (%) Target vessel failure (%) 5 31 28 31 41 12 15 5 15 20 0. 27 0. 10 0. 003 0. 08 0. 02 46 22 0. 03 Overall MACE (%) 49 37 0. 20 ARC definite/probable stent thrombosis (%) 13 2 0. 07

Death from any cause % of Patients 60 50 40 Hazard ratio, 1. 56 P=0. 27 30 20 SBO 10 MI COPD MI Stroke PES Lung CA unknown 0 0 0. 5 1 1. 5 BMS 2 Years from stenting No. at risk BMS 39 37 31 22 12 PES 41 40 34 19 12

Myocardial infarction % of Patients 60 50 Hazard ratio, 0. 67 P=0. 10 40 30 BMS 20 PES 10 0 0 0. 5 1 1. 5 2 Years from stenting No. at risk BMS 39 30 23 15 10 PES 41 39 30 15 8

Target lesion revascularization % of Patients 60 50 40 Hazard ratio, 0. 38 P=0. 003 30 BMS 20 10 PES 0 0 0. 5 1 1. 5 2 Years from stenting No. at risk BMS 39 33 23 13 8 PES 41 40 32 17 10

Target vessel failure Cardiac death, MI, TVR % of Patients 60 BMS 50 Hazard ratio, 0. 65 P=0. 03 40 30 PES 20 10 0 0 0. 5 1 1. 5 2 Years from stenting No. at risk BMS 39 PES 41 28 38 19 27 11 13 6 7

Clopidogrel use % of Patients P=NS

Conclusions In saphenous vein graft lesions, compared to a similar bare metal stent, the Taxus™ PES resulted in:

Conclusions In saphenous vein graft lesions, compared to a similar bare metal stent, the Taxus™ PES resulted in: • Significant reduction in 12 -month binary angiographic restenosis, target lesion revascularization and target vessel failure

Conclusions In saphenous vein graft lesions, compared to a similar bare metal stent, the Taxus™ PES resulted in: • Significant reduction in 12 -month binary angiographic restenosis, target lesion revascularization and target vessel failure • Trends for lower target vessel revascularization, myocardial infarction

Conclusions In saphenous vein graft lesions, compared to a similar bare metal stent, the Taxus™ PES resulted in: • Significant reduction in 12 -month binary angiographic restenosis, target lesion revascularization and target vessel failure • Trends for lower target vessel revascularization, myocardial infarction • No difference in mortality and stent thrombosis