Randomized Trial to Compare Bilateral Versus Single Internal

Randomized Trial to Compare Bilateral Versus Single Internal Mammary Coronary Artery Bypass Grafting (CABG): One Year Results of the Arterial Revascularisation Trial (ART) DP Taggart, DG Altman, AM Gray, B Lees, F Nugara, LM Yu, H Campbell, M Flather, on behalf of the ART Investigators John Radcliffe Hospital Oxford, University of Oxford, Royal Brompton & Harefield NHS Foundation Trust London and Imperial College London ESC Hot Line 2010, Stockholm On Line publication in EHJ

o o Background CABG remains best therapy for severe CAD (SYNTAX trial) CABG is limited by eventual failure of vein grafts (50 -75% by 10 years) o 10 years after CABG an IMA risk of: • Death (x 1. 6), MI (x 1. 4), angina (x 1. 25), redo surgery (x 2) • Patency rate of IMA > 95% at 10 years (veins = 25% - 50%) o Benefits persist into 2 nd and 3 rd decade of follow up Effect of Arterial Revascularization on Survival: a Systematic Review of Studies comparing bilateral and single internal mammary arteries. David P Taggart, Roberto D’Amico, Douglas G Altman Lancet 2001; 358: 870 -5 o 4693 BIMA vs 11269 o Matched for age, gender, LV function, DM o HR for death with BIMA: 0. 80 [95% CI=0. 70 -0. 94] o NNT of 13 -16 (to prevent one death)

Use of BIMA in Routine Clinical Practice o Uncommon • <10% of CABG patients in Europe • <5% of CABG patients in USA o Potential reasons for NOT using BIMA • • • Technically more challenging Adds to duration of operation Increases early mortality Increases early major morbidity Increases risk of sternal wound breakdown

2 1 IMA RA 3 SVG 4

Trial Design o Protocol published (Trials 2006, 7: 7) o Funded: UK Medical Research Council (MRC) & British Heart Foundation (BHF) o Sample size • 3000 patients • 5% in 10 year mortality (from 25% to 20%) • 90% power, 5% alpha required 2928 patients o Two arm randomised trial • Randomised 1: 1 SIMA to BIMA • Supplementary vein/artery grafts as required o On or Off-pump procedure o Multi-centre (n=28 hospitals in 7 countries worldwide)

ART Endpoints o Primary • Survival at 10 years o Secondary • Cause specific & 30 day mortality • Need for re-intervention • Clinical events • Quality of Life (SF-36, Rose and Euro. Qol) • Cost effectiveness o Sub-groups • Diabetes • Age (<70 yrs vs >70 yrs) • On vs off pump • Radial artery vs vein grafts • Number of grafts • Impaired ventricular function

Randomized patients n= 3102 Allocated to SIMA N= 1554 Allocated to BIMA n= 1548 Received surgery, n= 1546 (99. 5%) SIMA, n= 1494 BIMA , n= 38 Other, n = 14 Did not receive surgery, n= 8 1 - 1 died prior to surgery - 2 surgery cancelled - 1 had PTCA - 4 withdrew from trial Received surgery, n= 1531 (98. 9%) BIMA, n= 1294 SIMA , n= 215 Other, n = 22 Did not receive surgery, n= 16 1 - 1 died prior to surgery - 3 surgery cancelled - 3 withdrew from surgery - 1 had PTCA - 8 withdrew from trial Treatment received unknown, n=1 1 • 22 Died • 1 Withdrew At 6 weeks follow-up, n= 1525 • 13 Died • 5 Lost to follow-up • 3 Unable to contact Notes 1 2 Patient consent for data collection (SIMA=2; BIMA=7) Including participants who died before 1 year follow up (SIMA=36; BIMA=38) • 19 Died • 2 Lost to follow-up At 6 weeks follow-up, n= 1517 • 18 Died • 4 Lost to follow-up • 3 Unable to contact • 1 Withdrew At 1 year follow-up, n= 1504 At 1 year follow-up, n= 1491 Analysed at 1 year follow-up 2, n= 1540 Analysed at 1 year follow-up 2, n= 1529

ART Patient Characteristics SIMA (n=1554) BIMA (n=1548) 63. 5 (9. 1) 63. 7 (8. 7) 86% 85% 23. 4% 24% 7. 9% 7. 6% 43. 8% 40% Prior stenting 16% 15. 6% Prior CVA 3. 1% 2. 7% Peripheral arterial disease 7. 6% 6. 6% Age: years mean (±SD) Male Diabetes Urgent CABG Prior myocardial infarction

ART Surgery SIMA (n=1552) BIMA (n=1542) 40% 41. 8% 1 0. 7% 0. 5% 2 17. 7% 17. 8% 3 48. 5% 50. 4% 4+ 33. 2% 31. 3% 199 (58) 222 (61) Off-Pump Grafts Surgery length: mins mean (SD) Ventilation length: mins mean (SD) 863 (3293) Δ 23 mins 968 (3029) 105 mins Duration ITU stay: hours mean (SD) 38 (106) 41 (94) 3 hours Duration of post-op stay: days mean (SD) 7. 5 (7. 6) 8. 0 (7. 4) 0. 5 days Re-exploration for any cause 3. 5% 4. 3% Blood transfusion 12% Intra Aortic Balloon Pump 3. 7% 4. 4% Renal support 4. 4% 5. 9%

ART Outcomes 30 days 1 year SIMA (n=1552) BIMA (n=1542) All Mortality 1. 2% CVA 1. 2% 1. 0% MI 1. 5% 1. 4% Revasc 0. 4% 0. 7% Wound reconstruction 0. 6% 1. 9% All Mortality 2. 3% 2. 5% CVA 1. 8% 1. 5% MI 2. 0% Revasc 1. 3% 1. 8% Δ 1. 3%

ART Summary and Conclusions o ART is largest RCT in cardiac surgery comparing two operations • Confirms feasibility of international multi-centre RCT o Shows that routine use of BIMA is feasible in CABG patients o Testament to safety of contemporary CABG with 1 or 2 IMA • 30 day mortality 1. 2%; 1 year mortality 2. 5% o Use of BIMA does not increase • • • 30 day or 1 year mortality duration of post op stay risk of stroke, MI, revascularization o Use of BIMA results in a slight increase in the risk of sternal wound reconstruction by 1. 3% o ART is funded for 10 years to determine if BIMA reduce mortality and need for repeat revascularization (expected completion 2015) o ART will also report on costs, cost-effectiveness & Qo. L measures

ART Participating Centres (n=28)

ART Trial Steering and Data Monitoring Committees