dr akhil kapur london chest hospital, barts and the london nhs trust, london, uk on behalf of the...
TRANSCRIPT
Dr Akhil Kapur London Chest Hospital, Barts and the London NHS Trust, London, UK
On behalf of the CARDia InvestigatorsFriday 30th January 2009
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Revascularisation in Diabetic Patients with Multivessel Disease
• No specific randomised comparison of CABG and PCI until now
• Largest randomised comparison to date
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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%
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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
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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
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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2 withdrawn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2 withdrawn
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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
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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
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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
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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
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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)
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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%
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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)
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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)
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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
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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
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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
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Test of non inferiority of PCI vs. CABG for primary
endpoint - upper boundary of 1.3 (red line) shown
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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
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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
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Bristol Royal Infirmary Andreas Baumbach, Gianni Angelini
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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
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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