AA 2007

Bifurcation PCI and UK Trial Update

Rosie Swallow

Royal Bournemouth Hospital

AA 2007

No conflicts of interest

AA 2007

Randomized Study on Simple Versus Complex Stenting of Coronary Artery

Bifurcation Lesions.

The Nordic Bifurcation Study

Circulation. 2006;114: 1955-1961

AA 2007

Background

•  Optimal stenting strategy in coronary artery bifurcation lesions is unknown

•  Sirolimus coated stents reduce the rate of restenosis in

simple and complex coronary artery lesions

AA 2007

Nordic Bifurcation Study

•  Non blinded •  Randomised •  Multi-centre •  28 cardiology centres – Denmark, Sweden, Finland,

Norway and Latvia •  September 2004 – May 2005

AA 2007

Aim

Compare two stenting strategies in de novo bifurcation lesions using Sirolimus Eluting Stents (SES):

I. Stenting Main Vessel and optional stenting of side

branch (MV)

II. Stenting Main Vessel and Side Branch (MV+SB)

AA 2007

Randomised patients (n:413)

Stenting main vessel only (MV) (n: 207)

Stenting main vessel and side branch (MV+SB) (n: 206)

Clinical Follow up, 6 months (n: 207)

Clinical Follow up, 6 months (n: 206)

Scheduled angiographic Follow up after 8 months

(n: 176)

Scheduled angiographic Follow up after 8 months

(n: 182)

Angiographic Follow up available (n: 151)

Angiographic Follow up available (n: 156)

AA 2007

Inclusion criteria

•  Stable or unstable AP or silent ischemia •  Bifurcation lesion (including LMS in RCA dominant) •  Diameter of main vessel by visual estimate ≥2.5 mm •  Diameter of side branch by visual estimate ≥2.0 mm

AA 2007

Exclusion criteria

•  ST- elevation AMI within 24 hours

•  Expected survival <1year

•  Serum creatinine >200 µmol/l

•  Allergy to aspirin, clopidogrel or ticlopidine

•  Allergy to sirolimus

•  Left main bifurcation in a non-right dominant system

AA 2007

Primary end points

Combined end point at 6 months of : •  Cardiac death •  Myocardial infarction •  Stent thrombosis •  Target vessel revascularisation

AA 2007

Secondary end points

•  Combined end point of cardiac death, index lesion MI, target lesion revascularization (TLR), stent thrombosis

•  Procedure related biomarker increase •  Angiographic follow-up after 8 months

AA 2007 AA 2007

AA 2007 AA 2007

AA 2007

AA 2007 AA 2007

AA 2007 AA 2007

AA 2007 AA 2007

AA 2007

QCA Analysis at 8/12

307 patients MV MV+SB p (n:151) (n:156)

MLD SB (mm) 1.52 ± 0.58 1.86 ± 0.60 <0.001 late lumen loss SB (mm) -0.04 ± 0.52 0.2 ± 0.57 <0.001

Restenosis MV (%) 4.6 5.1 0.84 Restenosis SB(%) 19.2 11.5 0.062

AA 2007

Study Limitations

•  Open design

•  No ischaemia testing

•  Underpowered given low MACE rate

•  Variety of lesion types and locations

•  Clinical follow up at 6/12

•  Angiography at 8/12

•  Long term results not known

AA 2007

Conclusions

•  Excellent 6/12 clinical and 8/12 angiographic results •  Procedural success rates high, MACE low, angiographic

restenosis low, independent of stenting strategy •  Reduced procedure and fluoroscopy times, reduced

contrast and reduced risk of biomarker elevation in simple strategy

•  Simple strategy recommended as routine for bifurcations

AA 2007

Balloon-pump assisted Coronary Intervention Study (BCIS-1)

Study Update

A British Cardiovascular Intervention Society Project

Funded by Datascope, Cordis and Lilly

AA 2007

Study Design

•  Prospective, open, multi centre, randomised trial

•  Randomisation to Elective IABP or No Planned IABP

•  Sample size 300

•  Follow-up to hospital discharge or 28 days after randomisation

•  Six month follow-up ONS / GROS

AA 2007

Main Eligibility Criteria - Inclusion

•  Proposed single or multi-vessel PCI

•  Presence of both the following 1. EF<30%

2. Large area of myocardium at risk (one of the following)

– Unprotected LMS target lesion

–  Jeopardy score ≥8

–  Target vessel provides collateral supply to an occluded 2nd vessel which supplies > 40% myocardium

AA 2007

Main Eligibility Criteria - Exclusion

•  Systolic BP<85mmHg despite correction of hypovolaemia

•  Acute MI within previous 48 hours

•  Planned staged PCI within 28 days of index PCI

•  CI to IABP

AA 2007

Outcomes

Primary Outcome •  MACE at hospital discharge or

28 days

Secondary Outcomes •  Mortality at 6/12

•  Procedural complications

•  Bleeding complications

•  Access site complications

AA 2007

Institution Principal Investigator Study Co-ordinator Birmingham Heartlands Dr Mike Pitt Juliet Hulse Glenfield Hospital Dr Anthony Gershlick Amanda Lloyd Kings College London Dr Martyn Thomas Joanne Gregory Manchester Heart Centre Dr Doug Fraser Heather Iles-Smith Liverpool CTC Dr Rod Stables Heather Rodgers Royal Victoria Hospital Dr David Roberts Lesley Radford Royal Sussex County Hospital Dr Adam de Belder Nina Cooter Royal Bournemouth General Dr Rosie Swallow Nicki Lakeman St George's Dr Stephen Brecker Sue Brown St Thomas Hospital Dr James Coutts Alison Child University Hospital of North Staffordshire Dr Jim Nolan Julie Machin Wessex CTC Dr Nick Curzen Zoe Nicholas Western Infirmary Dr Keith Oldroyd Joanne Kelly Wythenshaw Hospital Dr Bernard Prendegast Teresa Coppenger Wolverhampton Heart & Lung Centre Dr James Cotton Andy Smallwood Yorkshire Heart Centre Dr Dan Blackman Claire Priestley

AA 2007

BCIS-1 Study Recruitment at 19th January 2006

0246810121416

Liverpo

ol CTC

RSCH Brighto

n

Kings C

ollege Lo

ndon

Yorkshir

e HC

Wessex C

TC

Western

Infirmary

St Georg

e's

St Thomas'

Birmingh

am Heartland

s

Royal V

ictoria

Blackpoo

l

Royal B

ournem

outh

Wolverhampton

Heart&Lung

Universi

ty of N

orth Staffo

rdshire

Total 88 patients

AA 2007

0

25

50

75

100

125

150

175

200

225

250

275

300

Dec-05

Feb-06

Apr-06

Jun-0

6

Aug-06

Oct-06

Dec-06

Feb-07

Apr-07

Jun-0

7

Aug-07

Oct-07

Dec-07

Feb-08

Apr-08

Jun-0

8

Aug-08

Actual per monthActual cummulative totalPredicted 10 pts per monthPredicted 15 pts per month

Average recruitment per site last 4 months is 0.7pts/month

BCIS-1 Projected Study Recruitment

End Sep 2008 End Feb 2008

AA 2007

Study Timelines

MREC submission 24th Mar 2005

MREC approval 28th Apr 2005

1st REC approval 13th May 2005

First patient 20th Dec 2005

New target of 25 – 30 centres

Invite more centres Jan/Feb 2007

Projected end recruitment Feb/Mar 2008

AA 2007

Join BCIS-1Centres - Contacts

Rod Stables rod.stables@ctc.nhs.uk

Simon Redwood simon.redwood@gstt.nhs.uk

Divaka Perera divaka.perera@gstt.nhs.uk

Jean Booth j.booth@rbht.nhs.uk

AA 2007

BBC ONE

The British Bifurcation Coronary study: Old, New and Evolving strategies

A randomised comparison of simple versus complex drug-eluting

stenting for bifurcation lesions

AA 2007

BBC ONE

Inclusion criteria >18 yrs

Stable or unstable angina

Bifurcation types I-IV suitable for stenting of both vessels

Vessel diameters ≥ 2.25mm side,

≥ 2.5mm main

AA 2007

BBC ONE

•  Simple – provisional T-stenting Following main vessel stenting, the side branch should not be treated further unless there is:

•  <TIMI 3 flow in the side branch •  Severe ostial pinching (>90%) of the side branch •  Threatened side vessel closure •  Side-branch dissection >type A

•  Complex – crush or culotte

AA 2007

BBC ONE

Primary endpoints (9 months)

•  Death •  Target vessel failure

–  main vessel or side branch TIMI<3 (after vasodilators) on further angiogram

–  main vessel or side branch undergoes attempted repeat PCI/CABG

•  Myocardial infarction

AA 2007

BBC ONE January 1st 2007

Steering committee: David Hildick-Smith Rod Stables Nick Curzen Keith Oldroyd

No. Patients recruited

310 RECRUITING CENTRES

CENTRE INVESTIGATOR ADMINISTRATOR RECRUITMENT

Brighton Hildick-Smith Cooter 82

Wolverhampton Cotton Smallwood 27

Coventry Glennon Gill 26

Bristol Baumbach Singh 25

Kings College Thomas Gregory 23

Liverpool Stables Matata 22

Dublin (St. James) Mulvihill Walsh 17

Glasgow Oldroyd Kelly 15

Southampton Curzen Kitt 15

Nottingham Henderson Burton 11

St George’s Brecker Brown 11

Bournemouth Talwar Lakeman 11

London (St. Thomas) Redwood Evans 8

Dublin (Beaumont) Foley McGrath 6

Stoke Butler Machin 3

Manchester Faz-Ordoubadi Gray 2

Birmingham Ludman Blount 1

Reading Orr Turner 1

Edinburgh Starkey Osborne 1

Birmingham (West) Varma Varma 1

AA 2007

0 10 20 30 40 50 60 70 80 90

BrightonWolverhampton

CoventryBristol

King's CollegeLiverpool

Dublin (St James)Glasgow

SouthamptonNottingham

St. GeorgesBournemouth

St ThomasDublin (Beaumont)

StokeManchester

ReadingBirmingham

Birmingham (West)Edinburgh

LeedsBlackpoolPapw orthLeicester

BBC ONE recruitment to January 1st 2007

(Ethics-approved centres)

AA 2007

BBC ONE current and target recruitment January 1st 2007

0

100

200

300

400

500

600

Sept

embe

r

Oct

ober

Nove

mbe

r

Dece

mbe

r

Jan-

06

Febr

uary

Mar

ch

April

May

June

July

Augu

st

Sept

embe

r

Oct

ober

Nove

mbe

r

Dece

mbe

r

Jan-

07

Febr

uary

Mar

ch

April

May

June

July

Target recruitmentCurrent recruitment

AA 2007

Study Timelines

•  Regulatory Approval (COREC/MHRA) Nov 2004 •  Pilot Study (Brighton Site Only) Jan 2005 •  First Wave of UK Sites recruiting Nov 2005 •  1st Interim analysis (220 pts) Sep 2006 •  2nd Interim analysis (350 pts) •  Final patient recruited July 2007 •  Follow up complete Mar 2008 •  Presentation May 2008

AA 2007

BBC 1 Contacts

David Hildick Smith david.hildick-smith@bsuh.nhs.uk

Nina Cooter Nina.Cooter@bsuh.nhs.uk

AA 2007

The CARDia Trial

Coronary Artery Revascularisation in Diabetes

AA 2007

•  Multi-centre, randomised, prospective comparison of PCI vs CABG for diabetics with MV or complex SVD

•  ‘Up-to-date’ strategy – DES, GPIIbIIIa, Arterial conduits, off-

pump, optimum glucose control •  Non Inferiority design, target 600 patients, revised to 500

Dec 2006

Study Design

AA 2007

Diabetic patients with multivessel disease or complex single vessel disease

Suitable for PCI or CABG

Inclusion and exclusion criteria met

CONSENT

Randomisation

CABG PCI +DES

No registry

No registry

No registry

AA 2007

Primary endpoint: •  Composite event rate at 1 year of death/non-fatal MI/

non-fatal stroke Major secondary endpoint: •  Further revascularisation procedures

•  Follow up is at 30 days, 6 months, 1 year, 2 years

AA 2007

CARDia Centres

The 8 centres London are:

Hammersmith St Mary’s St Thomas’ Kings College London Chest Harefield St Bart’s Royal Brompton

Hairmyers Glasgow Western

James Cook University

Dublin

Brighton Southampton

Papworth

LONDON Bristol

Birmingham

Nottingham

Blackpool Liverpool Sheffield

Manchester Stoke

AA 2007

Recruitment

0

100

200

300

400

500

600

Jan-05

Feb-05

March-05

April-05

May-05

Jun-05Jul-05

Aug-05

Sep-05

Oct-05

Nov-05

Dec-05

Jan-06

Feb-06

Mar-06

Apr-06

May-06

Jun-06Jul-06

Aug-06

Sep-06

Oct-06

Nov-06

Dec-06

Jan-07

AA 2007

Study Timelines

•  MREC approval was granted August 2001

•  First sites activated January 2002

•  Plan to finish recruitment April 2007

•  Application for additional funding to support follow up at 5 years.

AA 2007

CARDia Contacts •  Co-chief Investigator and Chairman of Steering Committee - Prof Roger

Hall (Norfolk and Norwich and Hammersmith Hospitals) •  Co-chief investigator and Project Manager - Dr Akhil Kapur (London

Chest Hospital) •  Director CTEU - Dr Marcus Flather (Royal Brompton Hospital) •  Study co-ordinator - Nicola Delahunty (CTEU, Royal Brompton Hospital) •  Study has been managed by CTEU at the Royal Brompton Hospital

since April 2006. Prior to this time it was managed at the Hammersmith Hospital.