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, StockholmOn Line publication in EHJ

Backgroundo CABG remains best therapy for severe CAD (SYNTAX trial)

o CABG is limited by eventual failure of vein grafts (50-75% by 10 years)

o 10 years after CABG an IMA risk of:

• Death (x1.6), MI (x1.4), angina (x1.25), redo surgery (x2)

• Patency rate of IMA > 95% at 10 years (veins = 25% - 50%)

o Benefits persist into 2nd and 3rd decade of follow up

o 4693 BIMA vs 11269o Matched for age, gender, LV function, DMo HR for death with BIMA:0.80 [95% CI=0.70 -0.94]

o NNT of 13-16 (to prevent one death)

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

Use of BIMA in Routine Clinical Practice

oUncommon• <10% of CABG patients in Europe• <5% of CABG patients in USA

oPotential 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

IMA

RA

SVG

1 2

3 4

Trial Designo 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 EuroQol)• 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

Notes1 Patient consent for data collection (SIMA=2; BIMA=7)2 Including participants who died before 1 year follow up (SIMA=36; BIMA=38)

Received surgery, n= 1531 (98.9%)BIMA, n= 1294SIMA ,n= 215Other, n = 22

Did not receive surgery, n= 161

- 1 died prior to surgery- 3 surgery cancelled- 3 withdrew from surgery- 1 had PTCA- 8 withdrew from trial

Treatment received unknown, n=11

At 6 weeks follow-up, n= 1517

At 1 year follow-up, n= 1491

• 19 Died• 2 Lost to follow-up

Analysed at 1 year follow-up2, n= 1529

Received surgery, n= 1546 (99.5%)SIMA, n= 1494BIMA ,n= 38Other, n = 14

Did not receive surgery, n= 81

- 1 died prior to surgery- 2 surgery cancelled- 1 had PTCA- 4 withdrew from trial

At 6 weeks follow-up, n= 1525

At 1 year follow-up, n= 1504

Analysed at 1 year follow-up2, n= 1540

• 13 Died• 5 Lost to follow-up• 3 Unable to contact

Allocated to BIMAn= 1548

Allocated to SIMAN= 1554

Randomized patientsn= 3102

• 18 Died• 4 Lost to follow-up• 3 Unable to contact• 1 Withdrew

• 22 Died• 1 Withdrew

ART Patient Characteristics

SIMA (n=1554) BIMA (n=1548)

Age: years mean (±SD) 63.5 (9.1) 63.7 (8.7)

Male 86% 85%

Diabetes 23.4% 24%

Urgent CABG 7.9% 7.6%

Prior myocardial infarction 43.8% 40%

Prior stenting 16% 15.6%

Prior CVA 3.1% 2.7%

Peripheral arterial disease 7.6% 6.6%

ART Surgery

SIMA(n=1552)

BIMA (n=1542)

Δ

Off-Pump 40% 41.8%

Grafts

1 0.7% 0.5%

2 17.7% 17.8%

3 48.5% 50.4%

4+ 33.2% 31.3%

Surgery length: mins mean (SD) 199 (58) 222 (61) 23 mins

Ventilation length: mins mean (SD) 863 (3293) 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% 12%

Intra Aortic Balloon Pump 3.7% 4.4%

Renal support 4.4% 5.9%

ART Outcomes

SIMA (n=1552)

BIMA (n=1542)

Δ

30 days

All Mortality 1.2% 1.2%

CVA 1.2% 1.0%

MI 1.5% 1.4%

Revasc 0.4% 0.7%

Wound reconstruction 0.6% 1.9% 1.3%

1 year

All Mortality 2.3% 2.5%

CVA 1.8% 1.5%

MI 2.0% 2.0%

Revasc 1.3% 1.8%

ART Summary and Conclusionso 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 & QoL measures

ART Participating Centres (n=28)City Hospital SurgeonsBrighton Royal Sussex County Forsyth, Trivedi, Hyde, Cohen, Lewis

Bydgoszcz Szpital Uniwersytecki Anisimowicz, Bokszanski

Cambridge Papworth Nair, Jenkins, (Ritchie), (Choong)

Cardiff University Hospital o f Wales O’Keefe, Von Oppell, M ehta

Edinburgh Edinburgh Royal Infirmary Zamvar

Gdansk M edical University Pawlaczyk, Szyndler

Hull Castle Hill Cale, Cowan, Grffin, Guvendik

Hyderabad Care Hospital M annam

Katowice M edical University of Silesia (Dept 1) Bochenek, Cisowski

Katowice M edical University of Silesia (Dept 2) Wos, (Widenka), Jasinski

Krakow John Paul II Sadowski, Gaweda, Rudzinski

Leicester Glenfield Spyt, Hickey, Sonowski

Liverpool Cardiothoracic Centre Kuduvalli (Dihmis)

London Harefield Gaer, Amrani, Bahrami, Soleimani

London King's College Hospital Desai, John

London Royal Brompton Pepper, De Souza, Trimlett, Petrou

London St George’s Chandrasekaran, Kanagasaby

M anchester Royal Infirmary Hasan, Keenan

M elbourne Austin and Repatriation M edical Centre Buxton, Seevanayagam, M atalanis, Rosalion

Newcastle Freeman Clark, Dark, Tocewicz, Pillay

New Delhi Escorts Heart Institute M ehawal, (Trehan)

Oxford John Radcliffe Taggart, Ratnatunga

Recife Heart Institute of Pernambuco M oraes

Rzeszow Oddzial Kardiochirurgii Widenka, Szymanik

Sheffield Northern General Briffa, Braidley, Cooper, Locke

St Polten Landesklinikum St Polten Podesser, Holzinger

Turin Ospedele M auriziano Casabona, Actis-Dato

Zabrze Silesian Centre for Heart Disease Szafron, Zembala , Pacholewicz

ART Trial Steering and Data Monitoring Committees

TRIAL STEERING COMMITTEE

Vermes,Geza Patient Lay Member Emeritus Professor of Hebrew Studies Oxford

Altman, Douglas Statistician Professor of Statistics in Medicine Oxford

Channon, Keith Cardiologist Professor of Cardiovascular Medicine Oxford

Collins, Rory Epidemiologist Professor of Epidemiology/Medicine Oxford

Dark, John Lead Surgeon Professor of Cardiac Surgery Newcastle

Farrell, Barbara Trials Advisor Co-Director, Resource Centre for Trials Oxford

Flather, Marcus Co-Principal InvestigatorDirector, CTEU, Royal Brompton Hospital London

Gray, Alastair Health Economist Professor of Health Economics Oxford

Pepper, John Lead Surgeon Professor of Cardiac Surgery London

Sleight, Peter CHAIRMAN Emeritus Professor of Cardiovascular MedicineOxford

Stables, Rod Cardiologist Consultant Cardiologist Liverpool

Taggart, David Principal Investigator Consultant Cardiac Surgeon Oxford

DATA MONITORING COMMITTEE

Julian, Desmond Cardiology Advisor Emeritus Professor of Cardiology London

Pocock, Stuart Statistician Professor of Statistics in Medicine London

Treasure, Tom Surgical Advisor Professor of Cardiothoracic Surgery London

Yusuf, Salim CHAIRMAN Professor of Medicine Hamilton,Ca