Dr Akhil Kapur London Chest Hospital, Barts and the London NHS Trust, London, UK

On behalf of the CARDia InvestigatorsFriday 30th January 2009

2

MY CONFLICTS OF INTEREST ARE

Grants: Cordis, Eli-Lilly, BMS-Sanofi, Boston Scientific, Medtronic

3

Revascularisation in Diabetic Patients with Multivessel Disease

• No specific randomised comparison of CABG and PCI until now

• Largest randomised comparison to date

4

CARDia Trial Design

Diabetic patients with multivessel diseaseor 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%

5

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

6

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

Endpoints

7

CARDia Patient flow Chart

254 patients1 died

7 withdrew2 no procedure

510 Pts randomised

CABG PCI

95% (242) in 1 year follow up 97% (248) in 1 year follow up

230=received CABG

14=cross over to PCI

256 patients

2 withdrew

253=received PCI

1=cross over to CABG

3 lost to follow up

2 withdrawn

4 lost to follow up

2 withdrawn

8

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  

9

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 treatedNon Insulin treated

  39.160.9

36.565.5

0.536 

Years with Diabetes

Yrs 10.4 10.1 0.804

Smoking Status %      

Non-smoker   63.4 63.3 0.928 

10

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 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

11

Procedural details

units Valid n CABG PCI

Time from randomisation to index procedure

median days 498 64 38

Time in hospital median days 494 9 1

12

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)

13

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%

14

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 1.77

(1.11,2.82)

TIMI Major Bleed at 1 year 6.1% 1.2% 0.009 0.19(0.06,0.67)

15

Primary composite outcome at 1 year

16

1 2 3

Individual 1 year outcomes Individual 1 year outcomes

3.2 %3.2 % (n=8)(n=8)

DeathDeath

p=0.97 p=0.09 p=0.07

Non fatal MINon fatal MI

3.2 %3.2 % (n=8)(n=8)

5.7%5.7% (n=14)(n=14)

9.8%9.8% (n=25)(n=25)

2.8%2.8% (n=7)(n=7)

0.4%0.4% (n=1)(n=1)

Non fatal strokeNon fatal stroke

CABG (n=248)

PCI (n=254)

17

CCS Class at 12 months

CCS Class

CABG baseline

n=244%

PCI baseline

n=250%

p value CABG 12 months n=244

%

PCI 12 monthsn=250

%

p value

0 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 0.4 0 1.4

IVa 1.2 0.8 0 0

IVb 0 0 0 0.5

18

Survival at 1 year CABG vs PCI

19

Death, MI, stroke and repeat revascularisation

20

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% 0.023

21

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

22

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

23

Test of non inferiority of PCI vs. CABG for primary

endpoint - upper boundary of 1.3 (red line) shown

24

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

25

CARDia Participating Centres

Centre 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

26

CARDia Participating Centres continued

Centre Local investigator Patients recruited

City Hospital, Birmingham Teri Millane 12

Royal Victoria, Blackpool David Roberts 11

Beaumont, Dublin David Foley 11

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 4

City Hospital, Nottingham Kamran Baig, Rob Henderson 3

CTC, Liverpool Rod Stables 3

Northern General, Sheffield Ever Grech 2

Harefield Hospital Charles Ilsley 1

Mayday, Surrey Kevin Beatt 1