Left Main Stem Intervention Trials

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Left Main Stem InterventionTrials Registries

• Keith D. Dawkins MD FRCP FACCSouthampton
  University Hospital
• UK

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Presenter Disclosure Information

• The following relationships exist related to this
• Presentation.
• Advisory Board or Consultant
• Abbott
• Boston Scientific Corporation
• ConorMed
• Eli Lilly
• Guidant
• Nycomed

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Assessing the Left Main Data

• Anatomy Ostium, Body, Bifurcation
• Elective vs. Emergency
• Surgical candidate or not?
• Left Ventricular Function
• Protected or not?
• Co-Morbidity Diabetes, Renal impairment
• Technical Approach Debulking, IVUS, IABP
• Drug Elution?

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Why is the Left Main special?

• Concern over haemodynamic stability
• Concern in relation to the consequences of
  coronary dissection
• Unknown comparative efficacy of the available
  bifurcation techniques
• Doubt concerning long-term results

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Left Main Stem Ultima Registry
N279
BMS 68.8, DES 0, POBA 15.1
Events ()
Cardiac Death
Q-AMI
MACE
CABG
Tan WA. Circ 20011041609-1614
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Bare Metal
Drug-Elution
The contribution of DES to LMS outcomes remains
uncertain!
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Left Main DES Restenosis
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DES Stent Thrombosis 1-2
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LMS Medical Treatment

Left Main Stem
Medical Treatment
Mortality (5 years) 36.5 Odds Ratio (vs. CABG)
0.32 0.15-0.70, p0.04
Yusuf et al. Lancet 1994344563-570
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CABG
PCI
OR
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http//www.ctsnet.org/file/SCTS2000pages116-121LMS
.pdf
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http//www.ctsnet.org/file/SCTS2000pages116-121LMS
.pdf
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Left Main Stem CABG Mortality
N3904
Death ()
Beauford 12 mths
Yeatman 24 mths
French Registry 12 mths
Mack 1m
Lu 12 mths
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http//www.ctsnet.org/file/SCTS2000pages116-121LMS
.pdf
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CABG has not been standing still
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Graft PatencyLIMA, SVG and Radial artery grafts
Occluded ()
Radial
SVG
LIMA
Mean follow-up 565 511 days
Khot UN et al. Circ 20041092086-2091
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European Revascularisation
per million population
7.6
10.1
12
Unger F (2004)
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Graft Patency On-Pump vs. Off-Pump
Patency Rate ()
On-Pump
Off-Pump
Khan NE et al. N Engl J Med 200435021-28
Mean follow-up 3 months
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Length of hospital stay, mortality rate, and
long-term neurological function and cardiac
outcome appear to be similar in the two groups.
To definitively answer the remaining questions of
whether either strategy is superior, a
large-scale prospective randomized trial is
required.
Circ 20051112858-2864
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Evolution of Revascularization

• Off pump technique
• Less invasive approach
• Increased arterialrevascularization
• Optimal perioperative monitoring

?

• Improved technique
• Improved stent design
• DES

• Restenosis
• Repeat revascularization

• High costs
• Invasive

Over the last decade, the standard of care for
both CABG and PCI has continuously improved,
leveling the playing field.
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SynTax All-Comers Design
Run-In Qualification Phase
Site Selection
All patients with 3VD/LM
Heart Team (surgeon interventionalist)
amenable for only one treatment approach
amenable for both treatment options
Two Registry Arms
Randomized Arm N1800 (11)
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Run-in Phase Data Overall Results
8895
12072
Run-in phase data
3177
Total CABG patients
Total PCI patients
Total patients entered as of 12 May 2005
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Run-in Phase Data Overall Results
CABG (103 Sites)
86.4
PCI (104 Sites)
60.3
Mean of Patients/Site
30.5
26.0
22.3
8.3
Total Patients
3VD
Left Main
Total 8895 6215 2680
Total 3177 2317 860
Patient ratio of PCICABG is 13 Ratio of
PCICABG for both 3VD and LM disease is 13
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Run-In Phase Left Main Data
CABG (103 Sites)
PCI (104 Sites)
26.0
Mean of Patients/Site
14.5
7.1
8.3
2.7
1.8
2.6
2.3
1.9
1.5
Mean
Isolated
1VD
2VD
3VD
Total 2680 185 274 729 1492
Total 860 274 240 193 153
PCICABG ratio for LM3VD is 110
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Run-In Phase Left Main Data
North America
Europe
31.3
24.2
20.6
Mean of Patients/Site
12.4
8.1
6.7
8.4
7.9
2.9
2.1
1.8
0.8
3.8
2.2
2.4
2.0
1.8
2.0
1.4
0.7
Mean
Isolated
Mean
Isolated
1VD
2VD
3VD
1VD
2VD
3VD
CABG Total LM - 1867
CABG Total LM - 813
PCI Total LM - 648
PCI Total LM - 212
Similar rates types of LM procedures were
performed in Europe North America.
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Run-In Phase Left Main PCI Data
North America (27 sites)
Europe (77 sites)
8.4
7.9
Mean of Patients/Site
5.6
1.8
Total LM
Unprotected
Total 648 429
Total 212 48
Unprotected LM PCI procedures were performed 3X
more often in Europe than in North America.
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Left Main Disease Procedures
CABG PCI PCICABG Ratio
Europe 24.2 8.4 13
Belgium 29.4 4.4 17
France 20.2 9.1 12
Germany 21.0 8.1 13
Netherlands 23.7 18.7 11
UK 32.7 6.9 15
Mean number of patients per site
The Netherlands performs twice the number of LM
PCI, while Belgium performs half, versus the rest
of Europe
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Left 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 66
Average number of LM patients with PCI per site
The majority of LM PCI procedures in The
Netherlands are unprotected.
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Left 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 LM3VD
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SynTax Enrollment
Oct 14th 2005
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Randomized Data

DES
Left Main
None!
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DES LMS Registries

Patients (n) 102 95 85
Debulking 2.9 3.2 0
IVUS 86.3 28.4 ?
IABP 4.9 15.8 21.2
IIb/IIIa 7.8 29.5 28.5
19 protected LM
Park S-J. J Am Coll Cardiol 200545351-356 Valgim
igli M. Circ 20051111383-1389 Chieffo. Circ
2005111791-795
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DES Registries Bifurcation treatment

• Single stent
• Kissing stents
• Culotte
• Crush stents
• V stents
• T stents
• Reverse crush

Final Kissing balloons
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Left Main Major Adverse Cardiac Events
MACE Free ()
FU 12 months
FU 6 months
FU 17 months
Park S-J. J Am Coll Cardiol 200545351-356 Valgim
igli M. Circ 20051111383-1389 Chieffo. Circ
2005111791-795
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Left Main Death
Death ()
FU 12 months
FU 6 months
FU 17 months
Park S-J. J Am Coll Cardiol 200545351-356 Valgim
igli M. Circ 20051111383-1389 Chieffo. Circ
2005111791-795
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Multivariate Predictors
Distal Left Main Disease DES Use LVEF Parsonnet
Score Reference Vessel Diameter Shock
Presentation Troponin T gt0.02 µg/l
Valgimigli M. Circ 20051111383-1389
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Multivariate Predictors
Distal Left Main Disease DES Use LVEF Parsonnet
Score Reference Vessel Diameter Shock
Presentation Troponin T gt0.02 µg/l
Valgimigli M. Circ 20051111383-1389
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Conclusions

• 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