Left Main Disease

Georgios Sianos, MD, PhD, FESC1st Department of Cardiology

AHEPA University HospitalThessaloniki Greece

Round tablePercutaneous interventions in coronary arteries

of high risk patients32nd Panhellenic Congress, 20-22 October, Thessaloniki

11.30-13.00 Room Alexandros

Previous Recommendations

for Unprotected LMCA Stenosis

Guidelines for Percutaneous Coronary Interventions

The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology

Authors/Task Force Members: Sigmund Silber, Chairperson (Germany)*, Per Albertsson, (Sweden), Francisco F. Avilés, (Spain), Paolo G. Camici, (UK), Antonio Colombo, (Italy), Christian Hamm,

(Germany), Erik Jørgensen, (Denmark), Jean Marco, (France), Jan-Erik Nordrehaug, (Norway), Witold Ruzyllo, (Poland), Philip Urban,

(Switzerland), Gregg W. Stone, (USA), William Wijns, (Belgium)Eur. Heart. J 2005;26:804-847

Recommendation Class III

Recommendation Class IIb (C)

Anatomic variations

Ostial stenosis Mid shaft stenosis Distal stenosis

Left main Comlexities

Frequency of Distal LM location

SYNTAX trialHeterogeneity of the anatomy in the Left

Main Group

Favorable vs. Unfavorable LMD for PCI

Favorable for PCI

• Ostial LMD• Mid shaft LMD• Isolated LMD• LM diameter>3.5mm• No/mildly calcified• Patent RCA• Good LV function• Stable

Problematic for PCI

• Distal LM• Ostial LAD/LCX involvement• Sharp LAD/LCX angles• Heavy calcification• LM diameter<3.5 mm• Associated MVD• Associated valve pathology• Occluded RCA• Poor LV function• Urgent

* Studies with >100 patients per arm reported 2000-2008ND=no difference; n/a=not available/not reported

Contemporary Trials of LM PCI vs CABG(> 100 pts, 2000-8)

Trial* N Death MI Stroke Revasc

Sanmartin 2007 341

ND

NDCABG

better

MAIN-COMPARE

20081102

n/aLEMANS 2008 105

Palmerini 2006 311

Chieffo 2006 249PCI

better PCI better

Lee 2006 173ND ND

Makikallio 2008 287 ND

Brener 2008 287n/a n/a n/a

White 2008 343

Drug Eluting Stent for LeFT

Main (DELFT) Registry

Study population

April 2002 April 2004

358 consecutive patients with

de novo ULMCA disease

SES or PES

Meliga et al J Am Coll Cardiol. 2008 Jun 10;51(23):2212-9

DELFT K-M Survival Analysis – Death + MI

~20% emergent treatment

Meliga et al J Am Coll Cardiol. 2008 Jun 10;51(23):2212-9

1000,00

Days

One M

insu C

um

Surv

ival

500,000,00

0,0

0,2

0,4

0,6

0,8

1,0

RR: 2.11

1.37 <RR <3.2

RR: 1.68

0.42 <RR <4.78RR: 1.33

0.22 <RR <7.8

365 d (1y)

Whole: 83.4%

Elec: 86%

Emerg: 72.6%

P=0.005

730 d (2y) 1095d (3y)

Left Main Ostial and ShaftMulticenter Registry - 2 year F/U

Chieffo et al Circulation 2007;116(2):158-162

Death, n (%) 5 (3.4)

Cardiac Death 4 (2.7)

TLR, n (%) 1 (0.7)

TVR, n (%)* 7 (4.7)

MI, n (%) 0

MACE, n (%) 11 (7.4)

n = 147

Late and Very Late Stent ThrombosisMulticenter Registry

Stent Thrombosis - ARC Definitions

* 3 early ST; 1 late ST in a Taxus stent in LAD at 3 mos; none VLST

Chieffo et al Eur Heart J 2008 Jun 18

Definite Stent Thrombosis

4* (0.54%)

Probable Stent Thrombosis

3 (0.4%)

Possible Stent thrombosis

20 (2.7%)

n = 731

0.9%

MAIN-COMPAIRE studyHR for Clinical Outcomes DES vs. Contemporary CABG

Matched Cohort: 396 Pairs

•HR are for the stenting group, as compared with CABG group

Seung KB et al: N Engl J Med 2008; 358:1781-92

Hazard ratio*Outcome (95% CI) P

Death 1.36 (0.80-2.30) 0.26

Composite outcome (death, 1.40 (0.88-2.22) 0.15Q-wave myocardialinfarction, or stroke)

Target-vessel revascularization5.96 (2.51-14.10) <0.001

Wave 2 (396 pairs)

Time after index procedure (days)

LM: One vs Two Stents @ Distal Bifurcation

EFS from TLR @ 3 yrs

Cross-over

2 Stent

Techniques

89.2%

82.7%

97.3%94.8%

p (log-rank) = 0.0062

85.0%

94.8%

Taxus Cypher

%

RR 0.85; 95% CI 0.56 to 1.29

MACE at 1 year

4- 2 0 2-4 6 8

- 2.2% + 95% CI = 2.7%

Pre-specified margin 8%

Difference in MACE

Pnoninferiority Taxus vs. Cypher<.001

ISAR Left MainPrimary Endpoint: 1-Year MACE

305302

Mehilli J. et al. JACC 2009 53;1760-1768

Despite society (ACC/AHA/SCAI and ESC) negative

recommendations for elective LM PCI (Class IIb or III), recent data with DES indicates…

• Elective PCI (non-emergent) with DES is associated with favorable clinical outcomes up to 3 yrs

• LM ostial and shaft lesions have particularly good clinical outcomes, including low repeat revascularization frequency up to 2 years

• Stent thrombosis - esp. late and very late - has been uncommon (rare) in multiple series

Before SYNTAX

DES vs. CABG for LMCA Disease

• Matched comparisons of DES vs. CABG indicate similar “hard” clinical events (death, MI, stroke) but still higher revascularization rates with DES (∆ ~8% at 3 years FU)

• A simplified 1 stent “crossover” technique is favored with lower repeat revascularization cw more complex 2 stent techniques

• There were no significant differences when comparing SES vs. PES in the treatment of unprotected LM lesions (including repeat revascularization)

Before SYNTAX

DES vs. CABG for LMCA Disease

TAXUSn=903

PCIn=198

CABGn=1077

CABGn=897

no f/un=428

5yr f/un=649

PCIall captured w/

follow up

CABG2500

750 w/ f/uvs

Total enrollment N=3075

Stratification: LM and Diabetes

Two Registry ArmsRandomized Armsn=1800

Two Registry ArmsN=1275

Randomized ArmsN=1800

Heart Team (surgeon & interventionalist)

PCIn=198

CABGn=1077

Amenable for only one treatment approach

TAXUS*

n=903CABGn=897

vs

Amenable for bothtreatment options

Stratification: LM and Diabetes

LM33.7%

3VD66.3%

LM34.6%

3VD65.4%

23 US Sites62 EU Sites +

SYNTAX Trial Design

*TAXUS Express

Practice Changing Implications from the SYNTAX LM Cohort

• “Since noninferiority was not proven,

specific information for each subgroup is of

an observational nature and is hypothesis

generating.” NEJM 2009;360:961-72

• The left main subgroup was not powered for

MACCE, let alone the for individual

components of MACCE, nor for the SYNTAX

tertiles.

Complexity of CAD and Long-term Outcomes in patients with Left Main Disease Treated with DES or

CABG1,146 pts from the MAIN-COMPARE registry stratified by Syntax score

Park D-W, et al. J Am Coll Cardiol. 2011;57:2152-2159.

Contemporary Trials of LM PCI vs CABG

Trial* N Death MI Stroke Revasc

Sanmartin 2007 341

ND

NDCABG

better

MAIN-COMPARE

20081102

n/aLEMANS 2008 105

Palmerini 2006 311

Chieffo 2006 249PCI

better PCI better

Lee 2006 173ND ND

Makikallio 2008 287 ND

Brener 2008 287n/a n/a n/a

White 2008 343

SYNTAX 2008 705 NDPCI

betterCABG

better

* Studies with >100 patients per arm reported 2000-2008

ND=no difference; n/a=not available/not reported

Limited Exclusion Criteria

• Previous Coronary Intervention • Acute MI with Creatine

Kinase>2x• Concomitant Cardiac Surgery

Left Main Disease(isolated, +1, +2 or +3 vessels)

3 Vessel Disease(revasc all 3 vascular territories)

SYNTAX-LE MANS Patient PopulationDe novo disease

LE MANS Substudy(patients provided separate

informed consent)

SYNTAX-LE MANS Substudy Design

Angiography for all LE MANS patients at 15±1 months

Primary Endpoints:TAXUS® Express® Stent: Rate of long-term patency of treated left main lesion(s) by QCA

CABG: Ratio of occluded to placed grafts/anastomoses at 15 months

No formal statistical inferences between the two treatment groups were made due to the different primary endpoints for the TAXUS® Express® Stent PCI and CABG treatment groups

All RCT patients with LM

TAXUS*N=156

CABGN=115

271 patients consented at 49 sites (13 US, 36 EU)

15 mo angio performed

TAXUS*N=153

CABGN=115

TAXUS*N=149

CABGN=114

15 mo angio analyzed

3 pts died**

Morice MC et al. Circulation. 2010;121:2645-2653

SYNTAX-LE MANS Principal Results CABG Cohort

Definitions:Occlusion Ratio: ratio of ≥50% obstructed or 100% occluded grafts/anastomoses (visual estimate) to the numberof grafts/anastomoses placed*Proportion of patients with at least 1 obstructed/occluded graft

Gra

fts (

%)

Obstruction/occlusion Ratio at 15 mo (per graft)

10% (26/262)

Primary Endpoint(Per graft):

16%20

10

0

6% (15/262)

=100%

≥ 50% to <100% Per patient:

Obstruction/occlusion Ratio at 15 mo* (per patient)

27%

Pa

tie

nts

(%

)

30

10

0

20

18% (21/114)

9% (10/114)

=100%

≥ 50% to <100%

Morice MC et al. Circulation. 2010;121:2645-2653

Angiographic FU: Binary RestenosisTAXUS Cohort (n=145)

Definitions:Diameter stenosis was assessed by QCA

Pa

tie

nts

(%

)

<50% stenosis at 15 mo

134/145

Primary Endpoint:

LM Non-distal LM Distal

47/48 87/97

Pa

tie

nts

(%

)<50% stenosis at 15 mo

Morice MC et al. Circulation. 2010;121:2645-2653

Symptomatic Graft Occlusion & StentThrombosis to 12 Months

Left Main Subset

2.73.7

CABG TAXUS

P=0.49

Pa

tie

nts

(%

)

n=11 n=9

TAXUS (n=357)CABG (n=348) Location of 10 definiteSTs in 9 TAXUS pts:

LM stem (1)LM bifurcation (LM/LAD (1)

and LM/LCX (1)LAD(4)LCX (2)RCA (1)

5 MIs, 5 revascs and3 deaths

11 graft occlusions:2 MIs, 11 revascs,

0 deaths(and 1 ST after

revasc)

Morice MC et al. Circulation. 2010;121:2645-2653

Left Main Distal Stenting Techniques LM Distal PCI (211 LM lesions)

89% of provisional T-stenting lesions used only 1 stent; 9% used 2 stents

Modified T-

stenting

2%

Classic T-stenting,

Side Branch First

6%Classic T-stenting,

Main Vessel First

14%

Provisional T-

stenting

52%

Culotte/Trousers

11%

Crush

8%

V-stenting,

Kissing/Gun Barrel

7%

Y-stenting,

Touching Stents

0.5%

CABG MACCE (%)

TA

XU

S S

tent

MA

CC

E (%

)

50

30

40

20

10

0

10 20 30 40 50

Size of circle adjusted for number of patients

SYNTAX-One-year MACCE rates per siteCABG vs. TAXUS Express Stent

Circ Cardiovasc Intervent 2009;2:59-68

LMCA PCI is reasonable in pts with class III angina and > 50% LMmstenosis who are not eligible for CABG

Stenting of the LMCA as an alternative to CABG may be considered in pts with anatomic conditions that are associated with a low risk of PCI procedural complications and clinical conditions that predict an increased risk of adverse surgical outcomes

ACC/AHA 2009 Focused Updates for STEMI and PCI.Circulation 2009;120:2271–2306

Left main PCI: 2- or 3-vessel disease,SYNTAX score ≥ 33

Left main PCI: Isolated or 1-vessel ds.with LM distal bifurcation involvementLeft main PCI: 2- or 3-vessel disease,SYNTAX score ≤ 32

Left main PCI: Isolated or 1-vessel ds.with LM ostium/shaft involvement

ESC/EACTS Guidelines on MyocardialRevascularization

Wijns W et al: Euro Heart J. 29, 2010

In 2009, the ACC-AHA PCI Guidelines were updated and raised LM stenting from Class III to Class IIb (level B)1

In 2010, ESC-EACTS Guidelines revised and upgraded LM (isolated or in conjunction with 1 vessel disease) stenting from Class IIb （level C) to IIa (level B)2

1 Kushner et al. Circulation 2009; 120:2271-23062 Wijns et al. EHJ 2010

Guidelines into perspective…

PRECOMBAT: Patient FlowPark SJ et al. N Engl J Med 2011

Death, MI or Stroke

MACCE

PRECOMBATPark SJ et al. N Engl J Med 2011

PRECOMBAT: Ischemia-Driven TVRPark SJ et al. N Engl J Med 2011

PCI vs. CABG Surgery in Left MainCoronary Artery Disease

Meta-analysis of 4 randomized trials involving 1,611 ptsLEMANS/SYNTAX LM/PRECOMBAT/BOUDRIOT et al

Conclusion: MACCE rates are similar for PCI and CABG except in pts with triple-vessel disease, for whom CABG

is favored

Capodanno D, et al. J Am Coll Cardiol. 2011;58:1426-1432.

Until new data become available

patient selection based on

angiographic and clinical criteria,

patient preference and physician-

team experience will generally dictate

the best and most appropriate care

for patients with LM disease

Conclusions