Coronary Artery Revascularisation in Diabetes Trial Dr Akhil Kapur London Chest Hospital, Barts and the London NHS Trust, London, UK On behalf of the CARDia Investigators Friday 30th January 2009

MY CONFLICTS OF INTEREST ARE Grants: Cordis, Eli-Lilly, BMS-Sanofi, Boston Scientific, Medtronic

Revascularisation in Diabetic Patients with Multivessel Disease No specific randomised comparison of CABG and PCI until now Largest randomised comparison to date

CARDia Trial Design Diabetic patients with multivessel disease or complex single vessel disease Suitable for PCI or CABG Inclusion and exclusion criteria met CONSENT Randomisation Up to date CABG Optimal PCI stent +abciximab DES 72% BMS 28%

Main Exclusion Criteria Informed consent could not be obtained Age >80 years Previous CABG or PCI Left main stem disease Cardiogenic shock Recent ST elevation myocardial infarction Contraindications to abciximab, aspirin and clopidogrel

Endpoints Primary endpoint: Composite event rate at 1 year of death/non-fatal MI/non-fatal stroke (time to first event) Major secondary: Further revascularisation at 1 year Secondary Severe bleeding complications at 30 days New requirement for permanent dialysis Neurological morbidity Quality of life Cost difference between treatments Change in LV function

CARDia Patient flow Chart 510 Pts randomised CABG PCI 254 patients 1 died 7 withdrew 2 no procedure 256 patients 2 withdrew 230=received CABG 14=cross over to PCI 253=received PCI 1=cross over to CABG 3 lost to follow up 2 withdrawn 4 lost to follow up 2 withdrawn 95% (242) in 1 year follow up 97% (248) in 1 year follow up 26 25 5 26 23 24 24 24 24 24

Baseline Clinical Characteristics Variable Units CABG PCI p value Number in group   254 256 Age Years 63.6 64.3 0.434 Male % 77.9 70.7 0.065 Systolic Blood pressure mmHg 137.3 136.7 0.745 Diastolic blood pressure mmhg 73.3 73.6 0.730 Heart rate Beats/min 69.9 68.7 0.361 BMI Kg/m2 29.4 29.2 0.734 Ethnicity White 72.4 67.1 0.585 South Asian 20.1 25.9 Black 2.4 2.5 Other 4.4 4.7

Baseline Clinical Characteristics Variable Units CABG PCI p value Admission Type %   Acute 23.6 21.5 0.564 Elective 76.4 78.5 Diabetes Status Type 1 6.7 3.1  0.097  Insulin treated Non Insulin treated 39.1 60.9 36.5 65.5 0.536  Years with Diabetes Yrs 10.4 10.1 0.804 Smoking Status Non-smoker 63.4 63.3 0.928 

Baseline Clinical Characteristics Variable Units CABG PCI p value 3 vessel disease % 59.7 64.8 0.224 Hypertension history 80.6 76.6 0.273 Hyperlipidaemia history 87.3 92.9 0.033 Renal failure 4.0 5.5 0.425 Peripheral vascular disease history 9.5 9.4 0.954 Chronic lung disease history 5.6 3.5 0.289 Cerebrovascular disease history 13.1 11.3 0.543 HbA1c 7.9 0.599 Creatinine   107.0 104.2 0.634 LV function Normal or Good 59.3 55.4 0.853 EF 60.0 59.1 0.582

Procedural details units Valid n CABG PCI Time from randomisation to index procedure median days 498 64 38 Time in hospital 494 9 1

PCI procedural details Use prior to procedure of: aspirin - 100% clopidogrel - 95% abciximab - 95% --------------------------------------------------------------------------------- 3 vessel disease - 65% 3 vessels treated in these patients - 88% average no. of stents per patient - 3.6 average stent length - 71mm DES patients (cypher) - 72% (181) BMS patients - 28% (72)

CABG procedural details 3 vessel disease - 60% 3 vessels treated in these patients - 90% ---------------------------------------------------------------------------- average no of grafts - 2.9 LIMAs - 94% % with at least two arterial grafts - 17% % off pump - 31%

Results - Intention to treat analysis Adjudicated events post randomisation CABG (248) PCI (254) p value HR and 95% CI Death 3.2 % 3.2% 0.97 0.98 (0.37,2.61) Non fatal MI (Periprocedural MI) 5.7% (4.4%) 9.8% (4.7%) 0.088 (0.819) 1.77 (0.92,3.40) Non fatal stroke 2.8% 0.4% 0.066 0.14 (0.02,1.14) Death, MI and stroke at one year – primary outcome 10.5% 13.0% 0.393 1.25 (0.75,2.09) Further revascularisation 2.0% 11.8% <0.001 6.18 (2.40,15.94) Composite outcome of death, MI, stroke, repeat revasc at 1 year 11.3% 19.3% 0.016 (1.11,2.82) TIMI Major Bleed at 1 year 6.1% 1.2% 0.009 0.19 (0.06,0.67)

Primary composite outcome at 1 year

Individual 1 year outcomes p=0.97 p=0.09 p=0.07 9.8% (n=25) CABG (n=248) PCI (n=254) 5.7% (n=14) 3.2 % (n=8) 3.2 % (n=8) 2.8% (n=7) 0.4% (n=1) Death Non fatal MI Non fatal stroke

CCS Class at 12 months CCS Class CABG baseline n=244 % PCI baseline p value CABG 12 months PCI 12 months 15.5 15.1 0.719 88.5 71.3 0.001 I 67.1 72.6 7.4 16.6 II 11.0 7.5 3.7 9.4 III 4.9 3.6 0.5 0.9 IV 0.4 1.4 IVa 1.2 0.8 IVb

Survival at 1 year CABG vs PCI

Death, MI, stroke and repeat revascularisation

Subgroup - CABG vs PCI-DES Comparison of CABG vs DES in PCI group CABG n=248 PCI (DES) n=181 p value CABG vs DES Death 3.2% 3.9% 0.721 Non fatal MI 5.7% 7.7% 0.398 Non fatal stroke 2.8% 0% 0.023 Composite outcome of death, non fatal MI and non fatal stroke at one year – primary outcome 10.5% 11.6% 0.735 Further revascularisation at 1 year 2.0% 9.4% 0.002 Composite outcome of death, non fatal MI, non fatal stroke and repeat revasc at 1 year 11.3% 17.1% 0.094 TIMI Major Bleed at 1 year 6.1% 1.1%

Subgroup - CABG vs PCI-DES Composite endpoint at 1 year

Study Limitations Planned recruitment not achieved 510 patients out of 600 recruited – 85% Formal non-inferiority parameters not fulfilled (insufficient power) we did not match the predicted PCI event rate originally estimated to be lower than predicted CABG rate

Test of non inferiority of PCI vs Test of non inferiority of PCI vs. CABG for primary endpoint - upper boundary of 1.3 (red line) shown

CARDia: Main Conclusions First randomised comparison of coronary revascularisation in diabetes Broadly similar primary endpoint at 1 year More repeat revascularisation in the PCI group Rate of stroke in respective arms consistent with other interventional studies We will follow up patients for 5 years to increase power

CARDia Participating Centres Local investigator Patients Recruited Hammersmith Hospital, London Kevin Beatt, Punit Ramrakha 84 St Mary’s Hospital, London Iqbal Malik 62 London Chest Hospital Martin Rothman, Akhil Kapur 52 St James Hospital, Dublin Peter Crean 42 Royal Sussex County, Brighton Steve Holmberg, Adam de Belder 34 Bristol Royal Infirmary Andreas Baumbach, Gianni Angelini 33 James Cook University Hosp, Middlesboro Mark de Belder 32 Western Infirmary, Glasgow Keith Oldroyd 30 King’s College Hospital Martyn Thomas 27 Manchester Royal infirmary Fath Ordoubadi 19 Hairmyres Hospital Keith Oldroyd, Barry Vallance 13 St Thomas’ Hospital Simon Redwood, Graham Venn 12

CARDia Participating Centres continued Local investigator Patients recruited City Hospital, Birmingham Teri Millane 12 Royal Victoria, Blackpool David Roberts 11 Beaumont, Dublin David Foley St Bartholomew’s Hospital, London Richard Schilling, Akhil Kapur 10 Papworth Hospital, Cambridge Peter Schofield 8 Royal Brompton Hospital Carlo di Mario 4 North Staffs, Stoke Mark Gunning City Hospital, Nottingham Kamran Baig, Rob Henderson 3 CTC, Liverpool Rod Stables Northern General, Sheffield Ever Grech 2 Harefield Hospital Charles Ilsley 1 Mayday, Surrey Kevin Beatt