BBC ONEBBC ONE

David Hildick-SmithDavid Hildick-SmithSussex Cardiac CentreSussex Cardiac Centre

Brighton, UKBrighton, UK

on behalf of the BBC ONE Investigatorson behalf of the BBC ONE Investigators

BBC ONEBBC ONE

The The BBritish ritish BBifurcation ifurcation CCoronary oronary study: study:

OOld, ld, NNew and ew and EEvolving strategies volving strategies

a randomized comparison of simple versus a randomized comparison of simple versus complex complex

drug-eluting stenting for bifurcation lesionsdrug-eluting stenting for bifurcation lesions

TechniquesTechniques

Simple – stepwise provisional T-Simple – stepwise provisional T-stentingstenting

Complex – total lesion coverage: crush Complex – total lesion coverage: crush or culotte or culotte

(according to operator preference)(according to operator preference)

Study organisationStudy organisation

• Steering Committee: Steering Committee: Curzen, Stables, Oldroyd, Hildick-Curzen, Stables, Oldroyd, Hildick-SmithSmith

• Initiation visit: Initiation visit: CooterCooter

• Randomisation and data entry:Randomisation and data entry: secure e-CRF at secure e-CRF at www.www.e-dendrite.come-dendrite.com

• DSMB: DSMB: Walsh, Wilcox, ScraseWalsh, Wilcox, Scrase

• CEC: CEC: Thomas, MacCarthyThomas, MacCarthy • Monitoring visit: Monitoring visit: Cooter, Bennett, WilsonCooter, Bennett, Wilson

• Data management: Data management: Dendrite Clinical SystemsDendrite Clinical Systems

• Continous remote monitoring: Continous remote monitoring: Cooter, Bennett, Cooter, Bennett, HowarthHowarth

• Statistician: Statistician: ClaytonClayton

Inclusion criteriaInclusion criteria

• Bifurcation coronary artery disease Bifurcation coronary artery disease requiring stentingrequiring stenting

• Vessel diametersVessel diameters• ≥≥2.25mm side2.25mm side• ≥≥2.5mm main2.5mm main

Exclusion criteriaExclusion criteria

• Unprotected left main stem narrowing Unprotected left main stem narrowing ≥50%≥50%

• Primary angioplastyPrimary angioplasty• Cardiogenic shockCardiogenic shock• CTO of either bifurcation-related vesselCTO of either bifurcation-related vessel• Additional Type C or bifurcation lesions Additional Type C or bifurcation lesions

requiring PCIrequiring PCI• Left ventricular ejection fraction ≤20%Left ventricular ejection fraction ≤20%

Statistical hypothesisStatistical hypothesis

• Assumption:Assumption:

• Death, MI, TVF (at nine months) Death, MI, TVF (at nine months) • 10% vs 20% in the two groups10% vs 20% in the two groups

• Sample size of 400 patients would achieve 80% Sample size of 400 patients would achieve 80% power at a 5% significance level power at a 5% significance level

• To allow for patients lost to follow-up and To allow for patients lost to follow-up and protocol violations it is proposed to recruit 500 protocol violations it is proposed to recruit 500 patients to the study. patients to the study.

Technique (simple)Technique (simple)

• Stage 1Stage 1• Stent main vesselStent main vessel

Technique (simple)Technique (simple)

• Following main vessel stenting, the side branch Following main vessel stenting, the side branch should not be treated further unless there is:should not be treated further unless there is:

• <TIMI 3 flow in the side branch<TIMI 3 flow in the side branch• Severe ostial pinching (>90%) of the side Severe ostial pinching (>90%) of the side

branchbranch• Threatened side vessel closureThreatened side vessel closure• Side-branch dissection >type ASide-branch dissection >type A

• if any of these applies, the operator if any of these applies, the operator may may → → Stage 2Stage 2

Technique (simple)Technique (simple)

• Stage 2 Stage 2 • Kissing inflationKissing inflation

Technique (simple)Technique (simple)

• Following kissing inflations, the side branch Following kissing inflations, the side branch should not be treated further unless there is:should not be treated further unless there is:

• <TIMI 3 flow in the side branch<TIMI 3 flow in the side branch• Severe ostial pinching (>70%) of the side Severe ostial pinching (>70%) of the side

branchbranch• Threatened side vessel closureThreatened side vessel closure• Side-branch dissection >type ASide-branch dissection >type A

• if any of these applies, the operator if any of these applies, the operator may may → → Stage 3Stage 3

Technique (simple)Technique (simple)

• Stage 3Stage 3• T-stentT-stent

Technique (simple)Technique (simple)

• Mandatory kissingMandatory kissing

Technique (complex) Technique (complex)

• CulotteCulotte• wire both vesselswire both vessels• stent first vesselstent first vessel

Technique (complex) Technique (complex)

• CulotteCulotte• Rewire main vesselRewire main vessel• stent 2stent 2ndnd vessel vessel• mandatory kissingmandatory kissing

Technique (complex) Technique (complex)

• CrushCrush• stent side vesselstent side vessel• crush with crush with

balloon/stentballoon/stent

Technique (complex) Technique (complex)

• CrushCrush• stent mainstent main• recross siderecross side• mandatory kissingmandatory kissing

PRIMARY ENDPOINTPRIMARY ENDPOINT

composite at 9 months of:composite at 9 months of:

• DeathDeath• Target vessel failure Target vessel failure • Myocardial infarctionMyocardial infarction

SECONDARY ENDPOINTSSECONDARY ENDPOINTS

• DeathDeath• Myocardial infarctionMyocardial infarction• Target vessel failureTarget vessel failure• Angina status – CCS and Angina Angina status – CCS and Angina

indexindex• Repeat angiographyRepeat angiography

• Procedural successProcedural success• TIMI 3 flow and <30% stenosis main vessel, andTIMI 3 flow and <30% stenosis main vessel, and• TIMI 3 flow side branchTIMI 3 flow side branch

• Kissing balloons success Kissing balloons success • In-hospital MACEIn-hospital MACE• In-hospital serious adverse events (non-MACE)In-hospital serious adverse events (non-MACE)• Procedure duration, fluoroscopy, cGy.cmProcedure duration, fluoroscopy, cGy.cm22, ,

contrastcontrast• Procedural consumables (wires, balloons, Procedural consumables (wires, balloons,

stents)stents)

PROCEDURAL ENDPOINTSPROCEDURAL ENDPOINTS

Additional detailsAdditional details

• Operators >150 PCI/yrOperators >150 PCI/yr• (96% procedures took place at surgical centres)(96% procedures took place at surgical centres)

• TAXUS stentsTAXUS stents

• Clopidogrel and Aspirin for 9 monthsClopidogrel and Aspirin for 9 months

RecruitmentRecruitment

0

50

100

150

200

250

300

350

400

450

500

Dec-04Jun-05

Dec-05Jun-06

Dec-06Jun-07

Dec-07

Recruiting centresRecruiting centres

Wolverhampton, 42Coventry, 39

King's College, 33Southampton, 31

Bristol, 30Liverpool, 28Dublin (St J), 28

Glasgow, 27Nottingham, 20St Thomas, 20

Edinburgh, 15St George's, 14

Bournemouth, 13Dublin (Beaumont), 10

Birmingham, 8Manchester, 8

Stoke, 6Birmingham (West), 6

Leicester, 3Reading, 3

0 10 20 30 40 50 60 70 80

Brighton, 116

RESULTSRESULTS

Baseline characteristicsBaseline characteristics

Complex Complex (n=250)(n=250) Simple Simple (n=250)(n=250)

Age (years) mean Age (years) mean (SD)(SD)

64 (11)64 (11) 64 (10)64 (10)

% male % male 77%77% 77%77% BMI (kg/mBMI (kg/m22) mean ) mean (SD)(SD)

28 (5)28 (5) 28 (5)28 (5)

DiabetesDiabetes 28 (11%)28 (11%) 31 (13%)31 (13%) Smoking (current)Smoking (current) 43 (17%)43 (17%) 42 (17%)42 (17%) Family historyFamily history 103 (41%)103 (41%) 104 (42%)104 (42%) HypertensionHypertension 154 (62%)154 (62%) 142 (57%)142 (57%) HypercholesterolaeHypercholesterolaemiamia

189 (76%)189 (76%) 188 (76%)188 (76%)

Clinical presentationClinical presentation

Stable67%

ACS (troponin -ve)12%

ACS (troponin +ve)16%

ST elevation MI5%

Site of bifurcation lesionSite of bifurcation lesion

LAD/D182%

Cx/OM13%

RCA/branch4%

Other1%

Bifurcation types Bifurcation types (MEDINA)(MEDINA)

1,1,160%

1,1,09%

1,0,19%

1,0,04%

0,1,114%

0,1,03%

0,0,11%

Glycoprotein IIb/IIIa useGlycoprotein IIb/IIIa use

Complex Complex (n=248)(n=248)

Simple Simple (n=249)(n=249)

P valueP value

GPI usedGPI used 110 110 (44%)(44%) 70 70 (28%)(28%) <0.001<0.001

Lesion and stent Lesion and stent characteristicscharacteristics

Complex Complex (n=250)(n=250)

Simple Simple (n=250)(n=250)

Main vesselMain vessel

Stent diameter (mm; SD)Stent diameter (mm; SD) 3.2 (0.3)3.2 (0.3) 3.0 (0.3)3.0 (0.3) Stent length (mm; SD)Stent length (mm; SD) 22 (6)22 (6) 21 (6)21 (6) Stenosis pre-procedure Stenosis pre-procedure (%)(%)

85 (11)85 (11) 87 (10)87 (10)

Stenosis post-procedure Stenosis post-procedure (%)(%)

4 (16)4 (16) 3 (13)3 (13)

Lesion and stent Lesion and stent characteristicscharacteristics

Complex Complex (n=250)(n=250)

Simple Simple (n=250)(n=250)

Side branchSide branch

Stent diameter (mm; SD)Stent diameter (mm; SD) 2.6 (0.3)2.6 (0.3) -- Stent length (mm; SD)Stent length (mm; SD) 16 (5)16 (5) -- Stenosis pre-procedure Stenosis pre-procedure (%)(%)

68 (29)68 (29) 63 (31)63 (31)

Stenosis post-procedure Stenosis post-procedure (%)(%)

12 (24)12 (24) 37 (33)37 (33)

Lesion and stent Lesion and stent characteristicscharacteristics

CompleComplexx

SimpleSimple P valueP value

Total stented length Total stented length (mm; SD)(mm; SD)

41 (16)41 (16) 24 (10)24 (10) <0.001<0.001

500

SIMPLE250

COMPLEX250

SIMPLE 249

COMPLEX 248

1 withdrew consent,1 no treatment attempted

1 randomisation delay

SIMPLESIMPLE

Procedure

n=249

No stent to main vessel

n=42%

Stent to main vesselNo kiss

n=17268%

Stent to main vesselKissing balloons

n=6627%

Stent to main vesselT-stent to side

Kissing balloonsn=73%

COMPLEX COMPLEX (Culotte)(Culotte)

Procedure n=75

≥1 vessel not stented

n=5

7%

Stent to both vesselsFailed kiss

n=3

4%

Stent to both vesselsKissing balloons

n=67

89%

COMPLEX COMPLEX (Crush)(Crush)

Procedure n=169

≥1 vessel not stented

n=16

9%

Stent to both vessels

Failed kissn=31

18%

Stent to both vessels

Kissing balloonsn=122

72%

PRIMARY ENDPOINTPRIMARY ENDPOINTComposite Composite (9months)(9months) Death, MI, TVF Death, MI, TVF

ComplexComplex SimpleSimple P valueP value DeathDeath 22 (0.8%) (0.8%) 11 (0.4%) (0.4%) -- Myocardial Myocardial infarctioninfarction 28 28 (11.2%)(11.2%) 9 9 (3.6%)(3.6%) --

Target vessel Target vessel failurefailure 18 18 (7.2%)(7.2%) 14 14 (5.6%)(5.6%) --

Primary Primary endpointendpoint 38 38 (15.2%)(15.2%) 20 20 (8.0%)(8.0%)

0.0090.009HR 2.0 (1.2 to HR 2.0 (1.2 to

3.5)3.5)

0%

5%

10%

15%

20%C

umu

lativ

e %

de

ath

, M

I, T

VF

0 3 6 9

Follow-up time (months)

Complex

Simple

PRIMARY ENDPOINTPRIMARY ENDPOINTDeath, MI, TVFDeath, MI, TVF

ComplexComplex 250250 218218 214214 208208

SimpleSimple 250250 241241 234234 227227

p=0.009

MYOCARDIAL INFARCTIONMYOCARDIAL INFARCTION

0%

5%

10%

15%

20%C

um

ula

tive

pe

rce

nta

ge

0 3 6 9

Follow-up time (months)

ComplexSimple

p=0.001

Biomarker dataBiomarker data

Complex Complex (n=248)(n=248)

Simple Simple (n=249)(n=249)

CKCK 231 231 (93%)(93%) 233 233 (94%)(94%)

TroponinTroponin 222 222 (90%)(90%) 233 233 (94%)(94%)

CK or TroponinCK or Troponin 240 240 (97%)(97%) 244 244 (98%)(98%)

TARGET VESSEL FAILURETARGET VESSEL FAILURE

0%

5%

10%

15%

20%C

um

ula

tive

pe

rce

nta

ge

0 3 6 9

Follow-up time (months)

ComplexSimple

p=ns

Target vessel failureTarget vessel failure

ComplComplexex

SimpleSimple

No. patients No. patients 1818 (7.2%)(7.2%)

14 14 (5.6%)(5.6%)

Immediate CABG 2 (0.8%) 0

Inpatient CABG 1(0.4%) 0

Stent thrombosis (ARC definite)

5 (2.0%) 1 (0.4%)

Revascularisation Revascularisation (restenosis)(restenosis)

99 1212

Revascularisation (distant Revascularisation (distant lesion)lesion)

1 1

In-hospital MACEIn-hospital MACE

CompleComplexx

SimpleSimple P valueP value

No. patientsNo. patients 20 20 (8.0%)(8.0%) 5 5 (2.0%)(2.0%) 0.0020.002RR 4.0 (1.5 to RR 4.0 (1.5 to

10.5)10.5)

DeathDeath 1 0

Myocardial Myocardial infarctioninfarction

18 5

CABGCABG 3 0

In-hospital serious adverse In-hospital serious adverse eventsevents

(non-MACE)(non-MACE)

ComplexComplex SimpleSimple

No. patients No. patients 1010 44 Bleed (TIMI major) 3 1

Stroke 1 0

Cardiac tamponade 2 1

Perforation without tamponade

3 1

Transfusion 6 1

Left main stem dissection 1 1

Vascular surgery 0 1

Procedural endpointsProcedural endpoints

ComplComplexex

SimpleSimple P P valuevalue

Procedure timeProcedure time (mins; mean, (mins; mean, SE)SE)

78 (1.9)78 (1.9) 57 (1.6)57 (1.6) <0.001<0.001

Fluoroscopy time (min; mean, SE)mean, SE)

22 (0.8) 15 (0.7) <0.001

Diamentor (cGy.cm2; mean, mean, SE)SE)

7900 (350)

6140 (300)

<0.001

No. guidewires used No. guidewires used (mean, SE)(mean, SE)

3.11 3.11 (0.08)(0.08)

2.21 2.21 (0.06)(0.06)

<0.001

No. balloons used (mean, (mean, SE)SE)

3.97 (0.11)

2.26 (0.09)

<0.001

No. stents used (mean, SE)(mean, SE)2.21

(0.07)1.17

(0.04) <0.001<0.001

CONCLUSIONSCONCLUSIONS

• For unselected bifurcation lesions, a For unselected bifurcation lesions, a stepwise provisional T stent strategy stepwise provisional T stent strategy

is superior to a systematic dual is superior to a systematic dual stenting strategy in all domains:stenting strategy in all domains:

• procedural successprocedural success• procedural complicationsprocedural complications

• in-hospital and 9-month MACEin-hospital and 9-month MACE

CONCLUSIONSCONCLUSIONS

• Further studies will examine Further studies will examine whether there are bifurcation whether there are bifurcation subsets in which total lesion subsets in which total lesion

coverage may be advantageouscoverage may be advantageous