Left Main Stem Intervention Trials & Registries Keith D. Dawkins MD FRCP FACC Southampton University Hospital UK

Left Main Stem InterventionLeft Main Stem InterventionTrials & RegistriesTrials & Registries

Left Main Stem InterventionLeft Main Stem InterventionTrials & RegistriesTrials & Registries

Keith D. Dawkins MD FRCP FACCKeith D. Dawkins MD FRCP FACC

Southampton University HospitalSouthampton University Hospital

UKUK

http://www.crf.org/

2

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Advisory Board or Consultant:AbbottBoston Scientific CorporationConorMedEli LillyGuidantNycomed

Assessing the Left Main DataAssessing the Left Main Data

Anatomy: Anatomy: Ostium, Body, BifurcationOstium, Body, Bifurcation

Elective Elective vs.vs. Emergency Emergency

Surgical candidate or not?Surgical candidate or not?

Left Ventricular FunctionLeft Ventricular Function

Protected or not?Protected or not?

Co-Morbidity: Co-Morbidity: Diabetes, Renal impairmentDiabetes, Renal impairment

Technical Approach: Technical Approach: Debulking, IVUS, IABPDebulking, IVUS, IABP

Drug Elution?Drug Elution?

Why is the Left Main special?Why is the Left Main special?

Concern over Concern over haemodynamic stabilityhaemodynamic stability

Concern in relation to the Concern in relation to the consequences of coronary consequences of coronary dissectiondissection

Unknown comparative Unknown comparative efficacy of the available efficacy of the available bifurcation techniquesbifurcation techniques

Doubt concerning Doubt concerning long-term resultslong-term results

Balloon AngioplastyBalloon Angioplasty 1977

Bare metal stentsBare metal stents 1993

Drug-Eluting stentsDrug-Eluting stents 2002

Left Main Stem: Left Main Stem: Ultima RegistryUltima Registry

24.3

15.0

5.06.4

3.8

8.7 8.79.1

0

10

20

30

Three Months FUTwelve Months FU

Even

ts (

%)

Cardiac Death Q-AMI MACE

Tan WA. Circ 2001;104:1609-1614Tan WA. Circ 2001;104:1609-1614

CABG

BMS 68.8%, DES 0%, POBA 15.1%

N=279

Bare MetalBare Metal Drug-ElutionDrug-Elution

The contribution of DES to LMS outcomes remains uncertain! The contribution of DES to LMS outcomes remains uncertain!

Left Main DES: Left Main DES: RestenosisRestenosis

DES Stent Thrombosis ~1-2%DES Stent Thrombosis ~1-2%

LMS: Medical TreatmentLMS: Medical Treatment

++Left Main Stem Medical Treatment

Mortality (5 years) = 36.5%Odds Ratio (vs. CABG) = 0.32 [0.15-0.70], p=0.04

Mortality (5 years) = 36.5%Odds Ratio (vs. CABG) = 0.32 [0.15-0.70], p=0.04

Yusuf et al. Lancet 1994;344:563-570Yusuf et al. Lancet 1994;344:563-570

CABGCABG PCIPCI

OROR

http://www.ctsnet.org/file/SCTS2000pages116-121LMS.pdfhttp://www.ctsnet.org/file/SCTS2000pages116-121LMS.pdf


Left Main Stem: Left Main Stem: CABG MortalityCABG Mortality

5.0

11.4

2.6 2.3

6.04.5

5.9

14.0

0

5

10

15

20

25

Off- Pump On- Pump

Death

(%

)

Beauford12 mths

Yeatman24 mths

French Registry12 mths

Mack1m

Off/On PumpCCAB

Lu12 mths

N=3904


CABG has not been standing still…CABG has not been standing still…

Graft PatencyGraft PatencyLIMA, SVG and Radial artery graftsLIMA, SVG and Radial artery graftsGraft PatencyGraft PatencyLIMA, SVG and Radial artery graftsLIMA, SVG and Radial artery grafts

33.730.1

4.80

10

20

30

40

50

Khot UN et al. Circ 2004;109:2086-2091

Occ

luded

(%

)*

p=0.28

p<0.0001

Radial SVG LIMA

*Mean follow-up 565 ± 511 days

0

200

400

600

800

1000

1200

1400

2000 2001 2002

PCI ST CABG O- CABG

7.6% 10.1% 12%

per million populationper million population

European RevascularisationEuropean RevascularisationEuropean RevascularisationEuropean Revascularisation

Unger F (2004)Unger F (2004)

Graft Patency: Graft Patency: On-Pump On-Pump vs.vs. Off-Pump Off-PumpGraft Patency: Graft Patency: On-Pump On-Pump vs.vs. Off-Pump Off-Pump

98

88

80

84

88

92

96

100

Khan NE et al. N Engl J Med 2004;350:21-28

Pate

ncy

Rate

(%

)*

p<0.002

On-Pump Off-Pump

*Mean follow-up 3 months

Circ 2005;111:2858-2864Circ 2005;111:2858-2864

Length of hospital stay, mortality rate, and long-termLength of hospital stay, mortality rate, and long-term

neurological function and cardiac outcome appear toneurological function and cardiac outcome appear to

be similar in the two groups. To definitively answer thebe similar in the two groups. To definitively answer the

remaining questions of whether either strategy is superior,remaining questions of whether either strategy is superior,

a large-scale prospective randomized trial is required.a large-scale prospective randomized trial is required.

Evolution of Evolution of RevascularizationRevascularization

P C IC A B G

Over the last decade, the standard of care for both CABG and PCI has continuously improved, leveling the playing field.

+ Off pump Off pump techniquetechnique

+ Less invasive Less invasive approachapproach

+ Increased arterialIncreased arterialrevascularizationrevascularization

+ Optimal Optimal perioperative perioperative monitoringmonitoring

+ Improved Improved techniquetechnique

+ Improved Improved stent designstent design

+ DESDES

High costsHigh costs InvasiveInvasive

- RestenosisRestenosis- Repeat Repeat

revascularizatiorevascularizationn

?

Heart Team (surgeon & interventionalist)

amenable for only one treatment approach

Two Registry Arms

amenable for both treatment options

SynTax: SynTax: All-Comers DesignAll-Comers Design

All patients with 3VD/LM

TAXUS CABGvs

Randomized ArmN=1800 (1:1)

PCIall captured w/ follow up

CABG2750 captured

(750 w/ follow up)

Run-In Qualification Phase

Site Selection

Run-in Phase DataRun-in Phase Data: : Overall ResultsOverall Results

0

2,000

4,000

6,000

8,000

10,000

12,000

14,000

0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

8,000

9,000

10,000

Total # patients entered as of 12 May

2005

Run

-in p

hase

data

12072 8895

3177

Total # CABG patients

Total # PCI patients

0

10

20

30

40

50

60

70

80

90

100

PCI (104 Sites)

CABG (103 Sites)86.4

30.5

60.3

22.3 26.0

8.3

Patient ratio of PCI:CABG is 1:3Ratio of PCI:CABG for both 3VD and LM disease is 1:3

Mean #

of

Pati

ents

/Sit

e

Total Patients 3VD Left Main

Total 8895 6215 2680

Total 3177 2317 860

Run-in Phase Data: Run-in Phase Data: Overall ResultsOverall Results

0

5

10

15

20

25

30

35

40

45

50

Run-In Phase: Run-In Phase: Left Main DataLeft Main Data

PCI:CABG ratio for LM+3VD is 1:10

26.0

2.6

7.12.7

14.5

Mean Isolated +1VD

1.82.3 1.9 1.5

8.3

+2VD +3VD

Total 2680 185 274 729 1492

Total 860 274 240 193 153

PCI (104 Sites)

CABG (103 Sites)

Mean #

of

Pati

ents

/Sit

e

0

5

10

15

20

25

30

35

40

45

50

Run-In Phase: Run-In Phase: Left Main DataLeft Main Data

Similar rates & types of LM procedures were performed in Europe & North America.

PCI: Total LM - 212CABG: Total LM - 813

31.3

0.8

8.1

1.8

20.6

Mean Isolated +1VD

North America

3.8 2.0 1.4 0.7

7.9

+2VD +3VD0

5

10

15

20

25

30

35

40

45

50

PCI: Total LM - 648CABG: Total LM - 1867

24.2

2.16.7

2.9

12.4

Mean Isolated+1VD

Europe

2.2 2.4 2.0 1.8

8.4

+2VD +3VD

Mean #

of

Pati

ents

/Sit

e

Run-In Phase: Run-In Phase: Left Main PCI DataLeft Main PCI Data

0

2

4

6

8

10

12

14

North America (27 sites)Europe (77 sites)

8.4 7.9

5.6

1.8

Unprotected LM PCI procedures were performed 3X more often in Europe than in North America.

Mean #

of

Pati

ents

/Sit

e

Total LM UnprotectedTotal 648 429

Total 212 48

Left Main Disease Left Main Disease Procedures Procedures

CABG PCI PCI:CABG Ratio

Europe 24.2 8.4 1:3

Belgium 29.4 4.4 1:7

France 20.2 9.1 1:2

Germany 21.0 8.1 1:3

Netherlands 23.7 18.7 1:1

UK 32.7 6.9 1:5

Mean number of patients per site

The Netherlands performs twice the number of LM PCI, while Belgium performs half, versus the rest of Europe

Left Main PCI ProceduresLeft Main PCI Procedures

Total LM Unprotected%

Unprotected

Europe 8.4 5.6 66

Belgium 4.4 3.0 68

France 9.1 6.3 70

Germany 8.1 4.4 55

Netherlands 18.7 16.0 86

UK 6.9 4.6 66Average number of LM patients with PCI per site

The majority of LM PCI procedures in The Netherlands are unprotected.

Left Main PCI ProceduresLeft Main PCI Procedures

Total Isolated +1VD +2VD +3VD

Europe 8.4 2.2 2.4 2.0 1.8

Belgium 4.4 1.0 2.0 0.8 0.6

France 9.1 2.3 3.8 1.8 1.2

Germany 8.1 1.9 1.8 1.7 2.8

Netherlands 18.7 8.5 4.7 2.3 3.2

UK 6.9 1.8 2.4 1.7 1.0

Average number of LM patients with PCI per site

Almost half of Netherlands LM procedures are isolated LMs; approx. 1/3 of all LM in Germany are LM+3VD

SynTax EnrollmentSynTax Enrollment

445445416416

282282

163163

3737

Oct 14Oct 14thth 2005 2005

Randomized DataRandomized Data

DESDES

++

Left MainLeft Main

None!None!

DES + LMS RegistriesDES + LMS Registries

Patients (n)Patients (n) 102 95* 85

DebulkingDebulking 2.9% 3.2% 0%

IVUSIVUS 86.3%

28.4% ?

IABPIABP 4.9% 15.8%

21.2%

IIb/IIIaIIb/IIIa 7.8% 29.5%

28.5%

Park S-J. J Am Coll Cardiol 2005;45:351-356Park S-J. J Am Coll Cardiol 2005;45:351-356

Valgimigli M. Circ 2005;111:1383-1389Valgimigli M. Circ 2005;111:1383-1389

Chieffo. Circ 2005;111:791-795Chieffo. Circ 2005;111:791-795

*19 protected LM

DES Registries: DES Registries: Bifurcation treatmentBifurcation treatment

Single stentSingle stent

Kissing stentsKissing stents

CulotteCulotte

Crush stentsCrush stents

V stentsV stents

T stentsT stents

Reverse crushReverse crush

± Final Kissing balloons

Left Main: Left Main: Major Adverse Cardiac Major Adverse Cardiac EventsEvents

80.0 76.0

98.0

64.155.0

81.4

0.0

20.0

40.0

60.0

80.0

100.0

Drug Eluting Stents Bare Metal Stents

MA

CE F

ree (

%)

FU 12 months FU 6 months FU 17 months




Left Main: Left Main: DeathDeath

3.5

14.0

0.0

9.3

16.0

0.00.0

5.0

10.0

15.0

20.0

Drug Eluting Stents Bare Metal Stents

Death

(%

)

FU 12 months FU 6 months FU 17 months




Multivariate PredictorsMultivariate Predictors


Distal Left Main DiseaseDistal Left Main Disease

DES UseDES Use

LVEF %LVEF %

Parsonnet ScoreParsonnet Score

Reference Vessel DiameterReference Vessel Diameter

Shock PresentationShock Presentation

Troponin T >0.02 Troponin T >0.02 µµg/lg/l

6 5 4 3 2 1 0 1 2 3 4

DES Better BMS Better

Multivariate PredictorsMultivariate Predictors

Distal Left Main DiseaseDistal Left Main Disease

DES UseDES Use

LVEF %LVEF %

Parsonnet ScoreParsonnet Score

Reference Vessel DiameterReference Vessel Diameter

Shock PresentationShock Presentation

Troponin T >0.02 Troponin T >0.02 µµg/lg/l

6 5 4 3 2 1 0 1 2 3 4

DES Better BMS Better


ConclusionsConclusions

Randomized trials (DES vs. CABG) are required.

They are unlikely to be powered for lesion sub-sets because of variations in PCI approach.

In planning Left Main PCI, consider individual patient and lesion specific risk factors.

Plan the strategy…

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Left Main Stem Intervention Trials & Registries Keith D. Dawkins MD FRCP FACC Southampton University Hospital UK