1. 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

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 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%

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. 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

7. 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2 withdrawn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2 withdrawn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

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 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 

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
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
494 9 1

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

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

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
(1.11,2.82)
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. Individual 1 year outcomes
p= p= 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

17. 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

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%

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
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
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
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