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 Endpointso 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 SurgerySIMA

(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 minsVentilation length: mins mean (SD) 863 (3293) 968

(3029)105 mins

Duration ITU stay: hours mean (SD) 38 (106) 41 (94) 3 hoursDuration 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 OutcomesSIMA

(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, LewisBydgoszcz Szpital Uniwersytecki Anisimowicz, BokszanskiCambridge P apworth Nair, J enkins, (Ritchie), (Choong)Cardiff University Hospital of Wales O’Keefe, Von Oppell, MehtaEdinburgh Edinburgh Royal Infirmary ZamvarGdansk Medical University P awlaczyk, SzyndlerHull Castle Hill Cale, Cowan, Grffin, GuvendikHyderabad Care Hospital MannamKatowice Medical University of Silesia (Dept 1) Bochenek, CisowskiKatowice Medical University of Silesia (Dept 2) Wos, (Widenka), J asinskiKrakow J ohn P aul II Sadowski, Gaweda, RudzinskiLeicester Glenfield Spyt, Hickey, SonowskiLiverpool Cardiothoracic Centre Kuduvalli (Dihmis)London Harefield Gaer, Amrani, Bahrami, SoleimaniLondon King's College Hospital Desai, J ohnLondon Royal Brompton P epper, De Souza, Trimlett, P etrouLondon St George’s Chandrasekaran, KanagasabyManchester Royal Infirmary Hasan, KeenanMelbourne Austin and Repatriation Medical Centre Buxton, Seevanayagam, Matalanis, RosalionNewcastle Freeman Clark, Dark, Tocewicz, P illayNew Delhi Escorts Heart Institute Mehawal, (Trehan)Oxford J ohn Radcliffe Taggart, RatnatungaRecife Heart Institute of P ernambuco MoraesRzeszow Oddzial Kardiochirurgii Widenka, SzymanikSheffield Northern General Briffa, Braidley, Cooper, LockeSt P olten Landesklinikum St P olten P odesser, HolzingerTurin Ospedele Mauriziano Casabona, Actis-DatoZabrze Silesian Centre for Heart Disease Szafron, Zembala , P acholewicz

ART Trial Steering and Data Monitoring Committees

TRIAL STEERING COMMITTEEVermes,Geza Patient Lay Member Emeritus Prof essor of Hebrew Studies Oxf ordAltman, Douglas Statistician Prof essor of Statistics in Medicine Oxf ordChannon, Keith Cardiologist Prof essor of Cardiovascular Medicine Oxf ordCollins, Rory Epidemiologist Prof essor of Epidemiology/ Medicine Oxf ordDark, J ohn Lead Surgeon Prof essor of Cardiac Surgery NewcastleFarrell, Barbara Trials Advisor Co-Director, Resource Centre f or Trials Oxf ordFlather, Marcus Co-Principal I nvestigatorDirector, CTEU, Royal Brompton Hospital LondonGray, Alastair Health Economist Prof essor of Health Economics Oxf ordPepper, J ohn Lead Surgeon Prof essor of Cardiac Surgery LondonSleight, Peter CHAI RMAN Emeritus Prof essor of Cardiovascular MedicineOxf ordStables, Rod Cardiologist Consultant Cardiologist LiverpoolTaggart, David Principal I nvestigator Consultant Cardiac Surgeon Oxf ord

DATA MONITORING COMMITTEEJ ulian, Desmond Cardiology Advisor Emeritus Prof essor of Cardiology LondonPocock, Stuart Statistician Prof essor of Statistics in Medicine LondonTreasure, Tom Surgical Advisor Prof essor of Cardiothoracic Surgery LondonYusuf , Salim CHAI RMAN Prof essor of Medicine Hamilton,Ca