left main disease€¦ · • ostial lmd • mid shaft lmd • isolated lmd • lm...
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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