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:

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

QCA Analysis at 8/ patientsMVMV+SBp (n:151)(n:156) MLD SB (mm)1.52 ± ±0.60<0.001 late lumen loss SB (mm)-0.04 ± ± 0.57<0.001 Restenosis MV (%) Restenosis SB(%)

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 2 nd 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 InstitutionPrincipal InvestigatorStudy Co-ordinator Birmingham HeartlandsDr Mike PittJuliet Hulse Glenfield HospitalDr Anthony GershlickAmanda Lloyd Kings College LondonDr Martyn ThomasJoanne Gregory Manchester Heart CentreDr Doug FraserHeather Iles-Smith Liverpool CTCDr Rod StablesHeather Rodgers Royal Victoria HospitalDr David RobertsLesley Radford Royal Sussex County HospitalDr Adam de BelderNina Cooter Royal Bournemouth GeneralDr Rosie SwallowNicki Lakeman St George'sDr Stephen BreckerSue Brown St Thomas HospitalDr James CouttsAlison Child University Hospital of North StaffordshireDr Jim NolanJulie Machin Wessex CTCDr Nick CurzenZoe Nicholas Western InfirmaryDr Keith OldroydJoanne Kelly Wythenshaw HospitalDr Bernard PrendegastTeresa Coppenger Wolverhampton Heart & Lung CentreDr James CottonAndy Smallwood Yorkshire Heart CentreDr Dan BlackmanClaire Priestley

AA 2007 BCIS-1 Study Recruitment at 19 th January 2006 Total 88 patients

AA 2007 Average recruitment per site last 4 months is 0.7pts/month BCIS-1 Projected Study Recruitment End Sep 2008End Feb 2008

AA 2007 Study Timelines MREC submission24 th Mar 2005 MREC approval28 th Apr st REC approval13 th May 2005 First patient20 th Dec 2005 New target of 25 – 30 centres Invite more centresJan/Feb 2007 Projected end recruitmentFeb/Mar 2008

AA 2007 Join BCIS-1Centres - Contacts Rod Simon Redwood Divaka Jean

AA 2007 BBC ONE The B ritish B ifurcation C oronary study: O ld, N ew and E volving 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 1 st 2007 Steering committee: David Hildick-Smith Rod Stables Nick Curzen Keith Oldroyd No. Patients recruited 310 RECRUITING CENTRES CENTREINVESTIGATORADMINISTRATORRECRUITMENT BrightonHildick-SmithCooter82 WolverhamptonCottonSmallwood27 CoventryGlennonGill26 BristolBaumbachSingh25 Kings CollegeThomasGregory23 LiverpoolStablesMatata22 Dublin (St. James)MulvihillWalsh17 GlasgowOldroydKelly15 SouthamptonCurzenKitt15 NottinghamHendersonBurton11 St George ’ sBreckerBrown11 BournemouthTalwarLakeman11 London (St. Thomas)RedwoodEvans8 Dublin (Beaumont)FoleyMcGrath6 StokeButlerMachin3 ManchesterFaz-OrdoubadiGray2 BirminghamLudmanBlount1 ReadingOrrTurner1 EdinburghStarkeyOsborne1 Birmingham (West)Varma 1

AA 2007 BBC ONE recruitment to January 1 st 2007 (Ethics-approved centres)

AA 2007 BBC ONE current and target recruitment January 1 st 2007

AA 2007 Study Timelines Regulatory Approval (COREC/MHRA) Nov 2004 Pilot Study (Brighton Site Only) Jan 2005 First Wave of UK Sites recruiting Nov st Interim analysis (220 pts) Sep nd 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 Nina Cooter

AA 2007 The CARDia Trial C oronary A rtery R evascularisation in Dia betes

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 CABGPCI +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 LiverpoolSheffield Manchester Stoke

AA 2007 Recruitment

AA 2007 Study Timelines MREC approval was granted August 2001 First sites activated January 2002 Plan to finish recruitmentApril 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 Prior to this time it was managed at the Hammersmith Hospital.