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D R N A J E E B U L L A H S O F I
L P S I N S T I T U T E O F C A R D I O L O G Y
LMCA : Evolution of management
GABG to PCI
Timeline of myocardial revascularization in LMCA
 The left main coronary artery provides 84% of the blood flow to the left
ventricle in patients with right dominant coronary circulation.
 Left main coronary artery disease accounts for 4–9% of patients referred for
coronary angiography.
 In historical studies, 3-year mortality in patients with unprotected left main
coronary artery disease receiving only medical therapy (mainly nitrate and a β-
blocker) was nearly 50%.
Anatomy and pathophysiology
 The left main coronary artery has an average length of 10 mm (2–23 mm), with
a mean diameter of 3.9 ± 0.4 mm in women and 4.5 ± 0.5 mm in men.
 Divided into three parts: ostium, shaft, and distal segment.
 The ostium lacks an adventitia layer, has abundant smooth muscle cells, and
has the most elastic tissue of the coronary vessels; these histological features
might account for a particular response (for example, higher elastic recoil) to
PCI at this location. The shaft and distal segments have a trilayered
architecture (with intima, media, and adventitia), which is similar to other
epicardial vessels.
 LMCA blood flow peaks in diastole, reaching approximately 200 ml/min/100 g
at a velocity of 40–60 cm/s
 At the bifurcation, the shear forces peak at the carina, creating areas of high
endothelial shear stress.
 The development of atherosclerosis in the LMCA has been linked to flow
haemodynamics, with atherosclerotic plaques described at areas of low
endothelial shear stress in the lateral wall of the bifurcation, opposite to the
carina.
 Conversely, the carina is often free from disease, probably owing to the
protective effect of high shear stress against plaque formation.
 The length of the LMCA also influences stenosis location and morphology. In
short LMCA (<10 mm), lesions develop more frequently near the ostium than
in the bifurcation (55% versus 38%), whereas in long arteries, lesions develop
predominantly near the bifurcation (ostium 18% versus bifurcation 77%).
 Furthermore, ostial lesions more frequently have negative remodelling, larger
luminal areas, and less calcium than distal lesions.
Evaluation
Anatomical assessment
 A diameter stenosis of 50% has been historically used as the threshold for
considering revascularization.
 A negative correlation between visual diameter stenosis of unprotected LMCA,
measured with coronary angiography as a continuous metric, and survival has
been reported.
 Patients with diameter stenosis between 50% and 70% had significantly higher
survival than those with diameter stenosis > 70%.
 Angiography tends to underestimate the severity of left main coronary artery
disease
 Hermiller et al. showed that 89% of patients with an angiographically normal
left main coronary artery had some degree of disease when assessed by IVUS.
 Detailed anatomical or functional evaluation is warranted, particularly in cases
of intermediate diameter stenosis (40–70%).
 Using FFR as the reference standard (FFR ≤ 0.75), Jasti et al. proposed an
IVUS MLA threshold of 5.9 mm2 for predicting physiological significance. A
similar comparison (IVUS versus FFR) in an Asian population yielded a lower
IVUS MLA cut- off of 4.5 mm2.
 The LITRO study prospectively validated an IVUS- derived MLA cut- off of 6
mm2 for deferral of revascularization in patients with unprotected LMCA
disease. At 2 years, MACE rates and cardiac death- free survival were similar in
patients who were deferred (MLA ≥ 6 mm2) and those who underwent
revascularization (MLA < 6 mm2).
 The disagreement between angiography and this IVUS criterion for a
significant stenosis was substantial. One third of patients with an insignificant
angiographic stenosis of <30% had an MLA of <6 mm2, whereas 43% of
patients with angiographic LM stenosis ≥50% had a prognostically favorable
MLA of ≥6 mm.
 IVUS is a better tool for determining the anatomical extent of disease, FFR is
a better tool for assessing the hemodynamically significance of an LM stenosis.
 FFR may be limited by the frequent presence of significant downstream
stenoses, which may underestimate or overestimate the hemodynamic
significance of the LM lesion.
 However, this is of more concern when there is severe disease present in both
the left anterior descending and circumflex arteries.
 Fearon et al showed that when only one major branch of the left main has
severe disease, downstream disease does not have a clinically relevant impact
on the evaluation of intermediate LM stenosis with the pressure wire placed in
the nondiseased branch.
 Based on their findings, if the FFR of the LM is either ≤0.80 or >0.85, then it
can be assumed that the LM lesion is hemodynamically significant or
insignificant, respectively.
 However, if the FFR is between 0.81 and 0.85, then the hemodynamic
significance of the LM lesion cannot be accurately determined if the combined
FFR of the LM and the downstream disease is ≤0.45. In such situations, IVUS
guidance is preferred
 Coronary CT angiography. Noninvasive coronary CT angiography (CCTA) has
been recommended as the first- line diagnostic test for patients with suspected
coronary artery disease.
 The presence of atherosclerotic disease irrespective of the luminal obstruction
was associated with worse prognosis.
 CCTA can accurately identify patients with in- stent restenosis, even with
metallic stents
 FFR derived from coronary CT angiography. Blood- flow simulation using
patient- specific coronary geometries has recently been introduced into clinical
practice. The FFR derived from CCTA (FFRCT; HeartFlow, USA) has been
shown to have high diagnostic accuracy with invasive FFR as a reference
1 . O P T I M A L M E D I C A L T H E R A P Y
2 . P C I
3 . CA B G
TREATMENT
 A meta- analysis of the early studies showed that patients with
unprotected left main coronary artery disease had the greatest
survival benefit with surgical revascularization (OR 0.32, 95% CI
0.15–0.70, P = 0.0004), establishing CABG surgery as the
treatment of choice for these patients.
 In 1977, Andreas Grüntzig successfully attempted the first balloon angioplasty
for unprotected left main coronary artery disease; however, he subsequently
reported in 1979 that balloon angioplasty was not suitable for unprotected left
main coronary artery disease.
 The first series of studies showed that balloon angioplasty for unprotected left
main coronary artery disease was feasible in 94% of patients. However, a
periprocedural mortality of 9.1% and a survival of 36.0 % at 3 years was
prohibitive.
 The advent of bare- metal stents revived interest in PCI for unprotected left
main coronary artery disease, but the high restenosis rates with bare- metal
stents limited the use of the procedure to patients at high surgical risk.
 The development of drug- eluting stents (DESs) has markedly improved the
prognosis after PCI in patients with unprotected left main coronary artery
disease, with randomized trials demonstrating a similar survival with PCI and
CABG surgery at mid- term follow-up.
PCI vs CABG
 A number of risk score systems have been proposed over the years to guide
decision- making between PCI or CABG surgery in patients with unprotected
left main coronary artery disease, including anatomical, clinical, combined
(anatomic and clinical), and functional risk scores
 The SYNTAX score, which is based entirely on anatomical
characteristics (that is, bifurcation lesions, lesion length, severe calcification,
tortuosity, and thrombus), defines three categories of risk (low, intermediate,
and high) based on conventional thresholds (≤ 22, 23–32, and ≥ 33,
respectively)
 The SYNTAX score II incorporates not only anatomical but also clinical
variables (age, sex, left ventricular ejection fraction, serum creatinine
clearance, presence of left main coronary artery disease, peripheral vascular
disease, and chronic obstructive pulmonary disease plus the anatomical
SYNTAX score) into logistic formulas for estimating 4-year mortality after PCI
and CABG surgery
RCT Registry
 LE MANS
 Boudriot
 PRECOMBAT
 SYNTAX
 EXCEL
 NOBLE
 IRIS-MAIN (Asia)
 MAIN-COMPARE
(Korean)
Left Main RCTs of PCI vs CABG
Left Main RCTs of PCI vs CABG
SYNTAXES trial
Background
 SYNTAX trial was a non-inferiority trial that compared
PCI using first-generation paclitaxel-eluting stents with
CABG in patients with de-novo three-vessel and left
main CAD, and reported results up to 5 years
 SYNTAXES trial examined all-cause death after 10
years of follow-up in patients randomly assigned to
PCI or CABG
Methods
 SYNTAX Extended Survival (SYNTAXES) study is an
investigator-driven extension of follow-up of a multicentre, RCT
done in 85 hospitals across 18 North American and European
countries.
 Patients with de-novo three-vessel and left main CAD were
randomly assigned (1:1) to the PCI group or CABG group.
 Prespecified subgroup analyses were performed according to
the presence or absence of LMCA disease and Diabetes, and
according to coronary complexity defined by core laboratory
SYNTAX score tertiles
Data Primary End Point
 From March, 2005, to April,
2007, 1800 patients were
randomly assigned to the PCI
(n=903) or CABG (n=897) group.
 Vital status information at 10
years was complete for 841
(93%) patients in the PCI group
and 848 (95%) patients in the
CABG group.
 10-year all-cause
death
Results
 At 10 years, 244 (27%) patients had died after PCI and 211
(24%) after CABG (hazard ratio 1·17 [95% CI 0·97-1·41],
p=0·092)
 Among patients with TVD , 151 (28%) of 546 had died after PCI
versus 113 (21%) of 549 after CABG (hazard ratio 1·41 [95% CI
1·10-1·80])
 Among patients with LMCA Ds, 93 (26%) of 357 had died
after PCI versus 98 (28%) of 348 after CABG (0·90 [0·68-1·20],
pinteraction=0·019)
Kaplan-Meier curves for primary analysis of 10-year all-
cause death
Kaplan-Meier curves for prespecified subgroup analysis of 10-year
all-cause death
Kaplan-Meier curves for 10-year all-cause death in prespecified
SYNTAX score tertile subgroups
Forest plot of prespecified subgroup analyses of 10-year
all-cause death
Conclusion
 At 10 years, no significant difference existed in all-
cause death between PCI using first-generation
paclitaxel-eluting stents and CABG
 However, CABG provided a significant survival
benefit in patients with three-vessel disease, but
not in patients with LMCA Ds.
A P R O SP E C T I VE , R A N D O M I ZE D T R I A L
C O M P A R I N G E VE R O L I M U S - E L U T I N G ST E N T S
A N D B Y P A SS G R A F T SU R G E R Y I N SE L E C T E D
P A T I E N T S W I T H L E F T M A I N C O R O N A R Y
A R T E R Y D I SE A SE
FIVE-YEAR OUTCOME
EXCEL trial
Background Trial Design
• Subset analysis from the SYNTAX
trial suggested that DES may be an
acceptable option for pts with
LMCAD and low or moderate CAD
complexity
• Since SYNTAX, PCI and surgical
outcomes have both improved,
necessitating a contemporary trial
examining revascularization
alternatives in LMCAD
 The EXCEL trial included 1,905
patients with unprotected LMCA
disease with low or intermediate
SYNTAX scores randomly assigned
to PCI with contemporary
everolimus- eluting stents or to
CABG surgery.
 Primary outcome was
a composite of death, stroke,
or myocardial infarction
R
Follow-up: 1 month, 6 months, 1 year, annually through 5 years
Primary endpoint: Measured at a median 3-yr FU, minimum 2-yr FU
Study Design
2900 pts with unprotected left main disease
SYNTAX score ≤32
Consensus agreement of eligibility and equipoise by heart team
Yes
(N=1900)
No
(N=1000)
Enrollment
registry
PCI (Xience EES)
(N=950)
CABG
(N=950)
Stratified by diabetes, SYNTAX score and
center
Major Inclusion Criteria Major Exclusion Criteria
 Unprotected LMCAD with ≥70%
DS, or ≥50% - <70% with either i)
non-invasive evidence of LM
ischemia, ii) IVUS MLA ≤6.0
mm2, or iii) FFR ≤0.80
 Syntax score ≤32
 Clinical and anatomic eligibility for
both PCI and CABG as agreed to by
the local Heart Team
 Prior CABG or LM PCI anytime
 Prior non-LM PCI within 1 year
 Need for cardiac surgery other
than CABG
 Inability to tolerate DAPT for 1
year
 CK-MB >ULN
Protocol Procedures
PCI recommendations
• Complete revasc of all ischemic territories with EES
• Provisional LM bifurcation treatment preferred
• IVUS guidance strongly recommended
• DAPT pre-loading and treatment for ≥1 year
• Routine angiographic follow-up not permitted
CABG recommendations
• Performed w/ or w/o CPB per operator discretion
• Complete anatomic revascularization of all vessels
≥1.5 mm in diameter with ≥50% DS
• Arterial grafts strongly recommended
• Epi-aortic ultrasound and TEE recommended
• Clopidogrel use during FU allowed but not mandatory
Guideline-directed medical therapy for both groups
Results
 At 5 years, a primary outcome event had occurred in 22.0% of the
patients in the PCI group and in 19.2% of the patients in the CABG group
(difference, 2.8 percentage points; 95% confidence interval [CI], −0.9 to 6.5; P
= 0.13).
 Death from any cause occurred more frequently in the PCI group than in the
CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2
to 6.1).
 In the PCI and CABG groups, the incidences of definite cardiovascular
death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI,
−1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4
percentage points; 95% CI, −1.3 to 4.2) were not significantly different.
 All cerebrovascular events were less frequent after PCI than
after CABG (3.3% vs. 5.2%; difference, −1.9 percentage points;
95% CI, −3.8 to 0), although the incidence of stroke was not
significantly different between the two groups (2.9% and 3.7%;
difference, −0.8 percentage points; 95% CI, −2.4 to 0.9).
 Ischemia-driven revascularization was more frequent after
PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage
points; 95% CI, 3.7 to 10.0).
• PCI with 2nd generation DES (Xience) was noninferior
to CABG for clinical outcomes at 3 years following
revascularization of unprotected left main lesions
• Adverse clinical events were not uniformly distributed
from a temporal standpoint; hazard was highest with
CABG vs. PCI in the first 30 days. Between 30 days-
3 years, outcomes were inferior with PCI vs. CABG
CABG
(n = 957)
EES PCI
(n = 948)
EXCEL Results at 3Yrs
• Primary endpoint: Death/MI/stroke: PCI vs. CABG:
15.4% vs. 14.7%, pnon-inferiority = 0.018; psuperiority = 0.98
• Death/stroke/MI at 30 days: 4.9% vs. 7.9%, p = 0.008;
Between 30 days-3 years: 11.5% vs. 7.9%, p = 0.02
• 3-year stent thrombosis/graft occlusion: 0.7% vs. 5.4%,
p < 0.001; revascularization: 12.6% vs. 7.5%, p <
0.0001
Results
Conclusions
Stone GW, et al. N Engl J Med 2016;375:2223-5
Primary endpoint
pnoninferiority = 0.018
psuperiority = 0.98
%
Five-Year Outcomes EXCEL Trial
Conclusion
 In the EXCEL trial, treatment of patients with LMCAD and
visually-assessed low or intermediate SYNTAX scores with CoCr-
EES resulted in similar rates of the clinically meaningful
composite outcome of death, stroke or MI at 5 years.
 The early benefits of PCI due to reduced peri-procedural risk were
attenuated by the greater number of events occurring during
follow-up, such that at 5 years the cumulative mean time free
from adverse events was similar with both treatments
• The 3-year primary outcomes are confirmed at 5-years.
• PCI showed to have better outcomes in the initial period
• After 36 months, there is an inversion of the curves showing
better outcomes in the CABG group.
• CABG was associated with a reduced risk of ID-TVR
when compared to PCI.
A P R O SP E C T I VE , R A N D O M I ZE D , O P E N - L A B E L ,
N O N - I N F E R I O R I T Y T R I A L , C A R R I E D O U T A T 3 6
H O SP I T A L S I N L A T VI A , E ST O N I A , L I T H U A N I A ,
G E R M A N Y , N O R W A Y , SW E D E N , F I N L A N D ,
U N I T E D K I N G D O M , A N D D E N M A R K
E N R O L L M E N T : D E C E M B E R 2 0 0 8 T O J A N U A R Y
2 0 15
NOBLE Trial
 Inclusion Criteria
 Stable angina, unstable angina, or acute
coronary syndrome
 A significant left main lesion
 Visually assessed
stenosis diameter >50%
or fractional flow reserve
≤0.80
 Located in the ostium,
mid-shaft, or bifurcation
 No more than three additional non-
complex lesions
 Local interventional cardiologists and
cardiac surgeons determined that
equivalent revascularization could be
achieved with CABG or PCI
 Exclusion Criteria
 Additional non left main complex lesions
• Chronic total
occlusions
• Bifurcation lesions
requiring two stent
techniques
• Calcified or tortuous
vessel morphology
 ST-elevation infarction within 24 h
 Being considered too high-risk for CABG
or PCI
 Expected survival of less than 1 year
Primary Endpoint
 A composite of major adverse cardiac and cerebrovascular events
(MACCE)
 Death from any cause
 Non-procedural myocardial infarction
 Repeat revascularization
 Stroke
 The NOBLE trial included 1,201 patients randomly assigned to PCI with
biolimus- eluting or sirolimus- eluting stents or to CABG surgery.
 In Kaplan–Meier analyses at 5 years, MACCE rates were significantly
increased with PCI compared with CABG surgery (29% versus 19%; P =
0.0066), and the noninferiority hypothesis was not met.
 Mortality was similar in both groups, but CABG surgery was
associated with significant reductions in nonprocedural myocardial
infarction, stroke, and repeat revascularization.
 Procedural myocardial infarction was not assessed in this trial, and
the stent thrombosis rate was substantially higher than in the EXCEL trial,
probably reflecting the different stent types used in each trial.
 In addition, an inexplicably high rate of late stroke in the PCI group
contributed to the increased risk of MACCE associated with this procedure in
the NOBLE trial
Results
Primary endpoint: MACCE
HR 1·48 (1·11–1·96); p=0·0066
28·9%
19·1%
PCI did not show non-inferiority
and CABG was superior to PCI
Results
All-cause mortality
11.5%
9.5%
HR 1·07 (0·67–1·72); p=0·77
11·6%
9·5%
Results
Non-procedural myocardial infarction
HR 2·88 (1·40–5·90); p=0·004
6·9%
1·9%
Results
Total repeat revascularization
HR 1·50 (1·04–2·17); p=0·03
10·4%
16·2%
Results
Stroke
HR 2·25 (0·92–5·48); p=0·07
4·9%
1·7%
PCI CABG P–value
Definite ST or
symptomatic graft occlusion* 3%(9) 4%(15) 0·22
Procedural myocardial
infarction (post hoc) 5%(16/296) 7%(16/238) 0·52
Results
Secondary endpoints
*Kaplan-Meier 5 year estimates by intention-to-treat
PCI CABG P–value
Repeat
revascularization 16%(71) 10%(47) 0·032
Target lesion
revascularization 12%(50) 8%(36) 0·14
De novo lesion
revascularization 6%(24) 3%(11) 0·018
Target LMCA
revascularization 10%(41) 9%(33) 0·37
Results
Secondary endpoints
Kaplan-Meier 5 year estimates by intention-to-treat
Kaplan-Meier 5 year estimates by
intention-to-treat
4.9%
1.9%
K-M estimates
Results
SYNTAX score subgroups
4.9%
1.9%
K-M estimates
HR 1·88 (1·23–2·89); p=0·0031 HR 1·16 (0·76–1·78); p=0·48 HR 1·41 (0·62–3·20); p=0·41
SYNTAX score assessed by independent corelab (CERC)
Conclusions
PCI did not meet non-inferiority for the primary endpoint of
5-year MACCE compared to CABG
CABG was superior to PCI
PCI resulted in higher rates of non-procedural myocardial
infarctions
Repeat revascularization was higher after PCI, primarily due
to de novo lesions and non LMCA target lesion
revascularization
All-cause mortality was similar for PCI and CABG
IRIS-MAIN REGISTRY
SECULAR TRENDS IN LMCA DISEASE:
RESULTS FROM THE IRIS-MAIN REGISTRY
IRIS-MAIN REGISTRY
 A nonrandomized, multinational, multicenter
observational study
 Patients were recruited from 50 academic and
community hospitals in Asia (China, India, Indonesia, Japan,
Malaysia, South Korea, Taiwan, and Thailand)
OBJECTIVE METHODS
 To evaluate patient
characteristics and long-
term outcomes for the
treatment of LMCA disease
over time in “real-world”
clinical practice
 Authors analysed data
from a large “all-comers”
registry that includes
patients who received
medical therapy, PCI, or
CABG for unprotected
LMCA disease.
STUDY POPULATION
 Study population was a part of IRIS-MAIN registry
 5,833 with significant LMCA disease were identified
between January 1995 and December 2013 at 50
participating sites
 616, 2,866 & 2,351 were treated with Medical therapy
alone, PCI & CABG respectively
 Patients who had prior CABG and those who
underwent concomitant valvular or aortic surgery were
excluded
 For the analyses, 3 historical time periods were chosen on the
basis of the generation of stent used in PCI: wave 1 (BMS) for
1995 to 2002; wave 2 (first generation DES) for 2003 to 2006;
and wave 3 (second-generation DES) for 2007 to 2013.
Results: Trends of patient characteristics and treatments
 Over time, the proportion of patients treated with PCI rather than
CABG increased substantially, whereas the proportion of patients
who received medical therapy remained steady
 During the study period, there was an increase of age for all 3
treatments, and more patients tended to present with stable
angina.
 Among the patients who underwent coronary revascularization,
there was an increased risk of patient comorbidities and anatomic
complexity over time.
 Improved chronic pharmacotherapy was found for all treatment
groups, particularly in terms of greater use of antiplatelet agents
and statins.
 In the PCI group, the type of stents used dramatically changed,
and the number and length of stents significantly increased with
increasing disease complexities.
 Despite an increased proportion of patients with distal bifurcation
involvement, more patients were treated with the simple 1-stent
crossover technique.
 In the CABG group, over time, off-pump surgery was more
frequently performed, and the total number of grafts has
decreased.
 Grafting using the internal mammary artery was more frequently
performed, but adoption rates varied for the radial artery.
Follow Up
 Median follow-up time was 9.7 years, 5.6 years,
and 3.0 years for patients treated in waves 1, 2,
and 3, respectively
Patient Characteristics Over Time in Each
Treatment Stratum
Patient Characteristics Over Time in Each
Treatment Stratum
OUTCOMES
 Clinical outcomes of interest were
 All-cause death
 Serious composite outcome (death, MI, or stroke)
 Repeat revascularization
 Major adverse cardiac and cerebrovascular events
(MACCE)[defined as the composite of death, MI, stroke, and repeat
revascularization]
Trends in Medications and Procedural and Surgical
Characteristics Over Time in Each Treatment Stratum
Results
 Medical therapy group:
 Adjusted risks for mortality; composite of death, MI, or stroke; and MACCE
gradually decreased over time
 PCI group:
 Trends toward decreasing risks for mortality, composite outcomes, and
repeat revascularization were also statistically significant.
 CABG group:
 Risks for any clinical outcomes remained relatively stable, with exception of
decreasing risk of repeat revascularization
Risk-Adjusted Trends of Hazard Ratios for Clinical
Outcomes Over Time in Each Treatment Stratum
Risk-Adjusted Trends of Hazard Ratios for Clinical
Outcomes Over Time in Each Treatment Stratum
Results
 During all time periods Medically treated patients had an
extremely higher rate of mortality and composite of death, MI,
or stroke than those who received PCI or CABG.
 Risks of mortality and composite of death, MI, or stroke were
comparable between PCI and CABG
 Risks of repeat revascularization and MACCE were higher in
PCI than CABG group
 Adjusted hazard ratios for risks of all clinical outcomes after PCI
relative to CABG gradually decreased over time
 This suggest that gap in treatment effect between PCI and
CABG has been narrowed.
Risk-Adjusted HRs of Relative Clinical Outcomes
Between Treatment Strategies Over Time
Risk-Adjusted HRs of Relative Clinical Outcomes
Between Treatment Strategies Over Time
Secular Changes of Treatment Effect and Guideline Recommendations in Relation to
Medical Advances of Each Treatment Stratum for Left Main Coronary Artery Disease
CONCLUSIONS
 Patient risk profiles and treatment of medical and
revascularization therapy have evolved remarkably over time
among patients with unprotected LMCA disease
 Gap in treatment effect between PCI and CABG has
progressively diminished, mainly due to more improved
outcomes with PCI.
Revascularization for Unprotected Left MAIN
Coronary Artery Stenosis: COMparison of
Percutaneous Coronary Angioplasty versus
Surgical REvascularization from Multi-Center
Registry
( K O R E A N R E G I ST R Y )
The MAIN-COMPARE Study
Study Population
 Consecutive patients with
unprotected left main coronary
disease who received stenting and
underwent CABG between
January 2000 and June 2006.
 From the second quarter of 2003
(May 2003), DES have been
exclusively used as treatment
device for PCI at participating
centers.
January, 2000
Second quarter,
2003
June, 2006
Wave I
BMS CABG
Wave II
DES CABG
MAIN-COMPARE Registry
Stenting (BMS vs. DES) vs. CABG
Unprotected
LMCA disease
Unprotected
LMCA disease
Study Design
Inclusion Criteria Exclusion Criteria
 Patients with unprotected left main
disease (defined as stenosis of
more than 50%) who underwent
stenting or isolated CABG.
 Primary End Point
 Death
 Composite of death, Q-wave
myocardial infarction, or stroke
 Target-vessel revascularization
• Prior CABG
• Concomitant valvular or aortic
surgery
• ST-elevation MI
• Cardiogenic shock at presentation
January, 2000
Second quarter
(May), 2003
June, 2006
Wave I
LMCA disease
BMS (N=318) CABG (N=448)
Wave II
LMCA disease
DES (N=784) CABG (N=690)
MAIN-COMPARE Study
Stenting (BMS or DES) vs. CABG
PCI (N=1102) CABG(N=1138)Total (N=2240)
Asan Medical Center
PCI patients (N=1102)
Reason for PCI
4Without suitable bypass conduits
12Concurrent severe medical illness
2Current malignancy
3Limited life expectancy
8Age ≥ 80 years and poor performance status
1073 (97%)
Physician’s preference
-”good candidate for stenting or CABG”
Patient’s preference/ Patient refused surgery
-“poor candidate for stenting”
29 (3%)Physician refused surgery
-“poor candidates for CABG”
Asan Medical Center
Angiographic Characteristics
Variable
Stents
(n=1102)
CABG
(n=1138) P Value
Involved location 0.04
Ostium and/or mid-shaft 50.6 46.2
Distal bifurcation 49.4 53.8
Extent of diseased vessel <0.001
Left main only 25.2 6.2
Left main plus single-vessel disease 24.0 10.5
Left main plus double-vessel disease 26.0 26.3
Left main plus triple-vessel disease 24.8 57.0
Right coronary artery disease 35.9 70.7 <0.001
Restenotic lesion 2.9 1.2 0.005
DEATH (Overall PCI and CABG matched cohort: 542 pairs)
Death, Q-MI, or Stroke : Overall
Target-vessel revascularization (Over All)
Asan Medical Center
Hazard Ratios for Clinical Outcomes
(Overall PCI and CABG matched cohort: 542 pairs)
Overall Patients
(N=542 pairs)
Outcome
Hazard Ratio*
(95% CI) P value
Death 1.18 (0.77-1.80) 0.45
Composite outcome
(death, Q-wave myocardial infarction, or
stroke)
1.10 (0.75-1.62) 0.61
Target-vessel revascularization 4.76 (2.80-8.11) <0.001
*HR are for the stenting group, as compared with CABG group
(BMS and contemporary CABG matched cohort: 207pairs)
Death: BMS and contemporary CABG matched cohort: 207pairs
Death, Q-MI, or Stroke
BMS and contemporary CABG matched cohort: 207pairs
Target-vessel revascularization
BMS and contemporary CABG matched cohort: 207pairs
Asan Medical Center
Hazard Ratios for Clinical Outcomes
Wave 1
(N=207 pairs)
Outcome
Hazard Ratio*
(95% CI) P value
Death 1.04 (0.59-1.83) 0.90
Composite outcome
(death, Q-wave myocardial infarction, or
stroke)
0.86 (0.50-1.49) 0.59
Target-vessel revascularization 10.70 (3.80-29.90) <0.001
*HR are for the stenting group, as compared with CABG group
(BMS and contemporary CABG matched cohort: 207pairs)
DEATH: DES and contemporary CABG matched cohort: 396 pairs
Death, Q-MI, or Stroke
DES and contemporary CABG matched cohort: 396 pairs
Target-vessel revascularization
DES and contemporary CABG matched cohort: 396 pairs
Asan Medical Center
Hazard Ratios for Clinical Outcomes
Wave 2
(N=396 pairs)
Outcome
Hazard Ratio*
(95% CI) P value
Death 1.36 (0.80-2.30) 0.26
Composite outcome
(death, Q-wave myocardial infarction, or
stroke)
1.40 (0.88-2.22) 0.15
Target-vessel revascularization 5.96 (2.51-14.10) <0.001
*HR are for the stenting group, as compared with CABG group
(DES and contemporary CABG matched cohort: 396 pairs)
Conclusion
 In a cohort of patients with unprotected left main coronary artery disease, we
found no statistical significant difference in the risk of death and serious
composite outcomes (death, Q-wave myocardial infarction, or stroke) between
patients receiving stenting and those undergoing CABG.
 These results were consistent when comparing bare-metal stents or drug-
eluting stents with concurrent CABG controls, although a statistically
nonsignificant trend was noted toward higher risk in the analysis for drug-
eluting stents.
 However, the rate of target-vessel revascularization was significantly lower in
the CABG group than in the PCI group, regardless of stent type.
Changes in PCI Guideline Recommendations for
LMCA Disease
Changes in PCI Guideline Recommendations for
LMCA Disease
Changes in PCI Guideline Recommendations
for LMCA Disease
Recommendation for the type of revascularization in
patients with Left main CAD
Neumann FJ et al., European Heart Journal (2019) 40, 87–165
LMCA : Evolution of management  GABG to PCI
LMCA : Evolution of management  GABG to PCI

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LMCA : Evolution of management GABG to PCI

  • 1. D R N A J E E B U L L A H S O F I L P S I N S T I T U T E O F C A R D I O L O G Y LMCA : Evolution of management GABG to PCI
  • 2. Timeline of myocardial revascularization in LMCA
  • 3.  The left main coronary artery provides 84% of the blood flow to the left ventricle in patients with right dominant coronary circulation.  Left main coronary artery disease accounts for 4–9% of patients referred for coronary angiography.  In historical studies, 3-year mortality in patients with unprotected left main coronary artery disease receiving only medical therapy (mainly nitrate and a β- blocker) was nearly 50%.
  • 4. Anatomy and pathophysiology  The left main coronary artery has an average length of 10 mm (2–23 mm), with a mean diameter of 3.9 ± 0.4 mm in women and 4.5 ± 0.5 mm in men.  Divided into three parts: ostium, shaft, and distal segment.  The ostium lacks an adventitia layer, has abundant smooth muscle cells, and has the most elastic tissue of the coronary vessels; these histological features might account for a particular response (for example, higher elastic recoil) to PCI at this location. The shaft and distal segments have a trilayered architecture (with intima, media, and adventitia), which is similar to other epicardial vessels.  LMCA blood flow peaks in diastole, reaching approximately 200 ml/min/100 g at a velocity of 40–60 cm/s
  • 5.  At the bifurcation, the shear forces peak at the carina, creating areas of high endothelial shear stress.  The development of atherosclerosis in the LMCA has been linked to flow haemodynamics, with atherosclerotic plaques described at areas of low endothelial shear stress in the lateral wall of the bifurcation, opposite to the carina.  Conversely, the carina is often free from disease, probably owing to the protective effect of high shear stress against plaque formation.  The length of the LMCA also influences stenosis location and morphology. In short LMCA (<10 mm), lesions develop more frequently near the ostium than in the bifurcation (55% versus 38%), whereas in long arteries, lesions develop predominantly near the bifurcation (ostium 18% versus bifurcation 77%).  Furthermore, ostial lesions more frequently have negative remodelling, larger luminal areas, and less calcium than distal lesions.
  • 6.
  • 8. Anatomical assessment  A diameter stenosis of 50% has been historically used as the threshold for considering revascularization.  A negative correlation between visual diameter stenosis of unprotected LMCA, measured with coronary angiography as a continuous metric, and survival has been reported.  Patients with diameter stenosis between 50% and 70% had significantly higher survival than those with diameter stenosis > 70%.  Angiography tends to underestimate the severity of left main coronary artery disease  Hermiller et al. showed that 89% of patients with an angiographically normal left main coronary artery had some degree of disease when assessed by IVUS.  Detailed anatomical or functional evaluation is warranted, particularly in cases of intermediate diameter stenosis (40–70%).
  • 9.  Using FFR as the reference standard (FFR ≤ 0.75), Jasti et al. proposed an IVUS MLA threshold of 5.9 mm2 for predicting physiological significance. A similar comparison (IVUS versus FFR) in an Asian population yielded a lower IVUS MLA cut- off of 4.5 mm2.  The LITRO study prospectively validated an IVUS- derived MLA cut- off of 6 mm2 for deferral of revascularization in patients with unprotected LMCA disease. At 2 years, MACE rates and cardiac death- free survival were similar in patients who were deferred (MLA ≥ 6 mm2) and those who underwent revascularization (MLA < 6 mm2).  The disagreement between angiography and this IVUS criterion for a significant stenosis was substantial. One third of patients with an insignificant angiographic stenosis of <30% had an MLA of <6 mm2, whereas 43% of patients with angiographic LM stenosis ≥50% had a prognostically favorable MLA of ≥6 mm.
  • 10.  IVUS is a better tool for determining the anatomical extent of disease, FFR is a better tool for assessing the hemodynamically significance of an LM stenosis.  FFR may be limited by the frequent presence of significant downstream stenoses, which may underestimate or overestimate the hemodynamic significance of the LM lesion.  However, this is of more concern when there is severe disease present in both the left anterior descending and circumflex arteries.
  • 11.  Fearon et al showed that when only one major branch of the left main has severe disease, downstream disease does not have a clinically relevant impact on the evaluation of intermediate LM stenosis with the pressure wire placed in the nondiseased branch.  Based on their findings, if the FFR of the LM is either ≤0.80 or >0.85, then it can be assumed that the LM lesion is hemodynamically significant or insignificant, respectively.  However, if the FFR is between 0.81 and 0.85, then the hemodynamic significance of the LM lesion cannot be accurately determined if the combined FFR of the LM and the downstream disease is ≤0.45. In such situations, IVUS guidance is preferred
  • 12.  Coronary CT angiography. Noninvasive coronary CT angiography (CCTA) has been recommended as the first- line diagnostic test for patients with suspected coronary artery disease.  The presence of atherosclerotic disease irrespective of the luminal obstruction was associated with worse prognosis.  CCTA can accurately identify patients with in- stent restenosis, even with metallic stents  FFR derived from coronary CT angiography. Blood- flow simulation using patient- specific coronary geometries has recently been introduced into clinical practice. The FFR derived from CCTA (FFRCT; HeartFlow, USA) has been shown to have high diagnostic accuracy with invasive FFR as a reference
  • 13. 1 . O P T I M A L M E D I C A L T H E R A P Y 2 . P C I 3 . CA B G TREATMENT
  • 14.  A meta- analysis of the early studies showed that patients with unprotected left main coronary artery disease had the greatest survival benefit with surgical revascularization (OR 0.32, 95% CI 0.15–0.70, P = 0.0004), establishing CABG surgery as the treatment of choice for these patients.  In 1977, Andreas Grüntzig successfully attempted the first balloon angioplasty for unprotected left main coronary artery disease; however, he subsequently reported in 1979 that balloon angioplasty was not suitable for unprotected left main coronary artery disease.  The first series of studies showed that balloon angioplasty for unprotected left main coronary artery disease was feasible in 94% of patients. However, a periprocedural mortality of 9.1% and a survival of 36.0 % at 3 years was prohibitive.
  • 15.  The advent of bare- metal stents revived interest in PCI for unprotected left main coronary artery disease, but the high restenosis rates with bare- metal stents limited the use of the procedure to patients at high surgical risk.  The development of drug- eluting stents (DESs) has markedly improved the prognosis after PCI in patients with unprotected left main coronary artery disease, with randomized trials demonstrating a similar survival with PCI and CABG surgery at mid- term follow-up.
  • 16. PCI vs CABG  A number of risk score systems have been proposed over the years to guide decision- making between PCI or CABG surgery in patients with unprotected left main coronary artery disease, including anatomical, clinical, combined (anatomic and clinical), and functional risk scores  The SYNTAX score, which is based entirely on anatomical characteristics (that is, bifurcation lesions, lesion length, severe calcification, tortuosity, and thrombus), defines three categories of risk (low, intermediate, and high) based on conventional thresholds (≤ 22, 23–32, and ≥ 33, respectively)  The SYNTAX score II incorporates not only anatomical but also clinical variables (age, sex, left ventricular ejection fraction, serum creatinine clearance, presence of left main coronary artery disease, peripheral vascular disease, and chronic obstructive pulmonary disease plus the anatomical SYNTAX score) into logistic formulas for estimating 4-year mortality after PCI and CABG surgery
  • 17. RCT Registry  LE MANS  Boudriot  PRECOMBAT  SYNTAX  EXCEL  NOBLE  IRIS-MAIN (Asia)  MAIN-COMPARE (Korean) Left Main RCTs of PCI vs CABG
  • 18.
  • 19. Left Main RCTs of PCI vs CABG
  • 20.
  • 21.
  • 23. Background  SYNTAX trial was a non-inferiority trial that compared PCI using first-generation paclitaxel-eluting stents with CABG in patients with de-novo three-vessel and left main CAD, and reported results up to 5 years  SYNTAXES trial examined all-cause death after 10 years of follow-up in patients randomly assigned to PCI or CABG
  • 24. Methods  SYNTAX Extended Survival (SYNTAXES) study is an investigator-driven extension of follow-up of a multicentre, RCT done in 85 hospitals across 18 North American and European countries.  Patients with de-novo three-vessel and left main CAD were randomly assigned (1:1) to the PCI group or CABG group.  Prespecified subgroup analyses were performed according to the presence or absence of LMCA disease and Diabetes, and according to coronary complexity defined by core laboratory SYNTAX score tertiles
  • 25. Data Primary End Point  From March, 2005, to April, 2007, 1800 patients were randomly assigned to the PCI (n=903) or CABG (n=897) group.  Vital status information at 10 years was complete for 841 (93%) patients in the PCI group and 848 (95%) patients in the CABG group.  10-year all-cause death
  • 26. Results  At 10 years, 244 (27%) patients had died after PCI and 211 (24%) after CABG (hazard ratio 1·17 [95% CI 0·97-1·41], p=0·092)  Among patients with TVD , 151 (28%) of 546 had died after PCI versus 113 (21%) of 549 after CABG (hazard ratio 1·41 [95% CI 1·10-1·80])  Among patients with LMCA Ds, 93 (26%) of 357 had died after PCI versus 98 (28%) of 348 after CABG (0·90 [0·68-1·20], pinteraction=0·019)
  • 27. Kaplan-Meier curves for primary analysis of 10-year all- cause death
  • 28. Kaplan-Meier curves for prespecified subgroup analysis of 10-year all-cause death
  • 29. Kaplan-Meier curves for 10-year all-cause death in prespecified SYNTAX score tertile subgroups
  • 30. Forest plot of prespecified subgroup analyses of 10-year all-cause death
  • 31. Conclusion  At 10 years, no significant difference existed in all- cause death between PCI using first-generation paclitaxel-eluting stents and CABG  However, CABG provided a significant survival benefit in patients with three-vessel disease, but not in patients with LMCA Ds.
  • 32. A P R O SP E C T I VE , R A N D O M I ZE D T R I A L C O M P A R I N G E VE R O L I M U S - E L U T I N G ST E N T S A N D B Y P A SS G R A F T SU R G E R Y I N SE L E C T E D P A T I E N T S W I T H L E F T M A I N C O R O N A R Y A R T E R Y D I SE A SE FIVE-YEAR OUTCOME EXCEL trial
  • 33. Background Trial Design • Subset analysis from the SYNTAX trial suggested that DES may be an acceptable option for pts with LMCAD and low or moderate CAD complexity • Since SYNTAX, PCI and surgical outcomes have both improved, necessitating a contemporary trial examining revascularization alternatives in LMCAD  The EXCEL trial included 1,905 patients with unprotected LMCA disease with low or intermediate SYNTAX scores randomly assigned to PCI with contemporary everolimus- eluting stents or to CABG surgery.  Primary outcome was a composite of death, stroke, or myocardial infarction
  • 34. R Follow-up: 1 month, 6 months, 1 year, annually through 5 years Primary endpoint: Measured at a median 3-yr FU, minimum 2-yr FU Study Design 2900 pts with unprotected left main disease SYNTAX score ≤32 Consensus agreement of eligibility and equipoise by heart team Yes (N=1900) No (N=1000) Enrollment registry PCI (Xience EES) (N=950) CABG (N=950) Stratified by diabetes, SYNTAX score and center
  • 35. Major Inclusion Criteria Major Exclusion Criteria  Unprotected LMCAD with ≥70% DS, or ≥50% - <70% with either i) non-invasive evidence of LM ischemia, ii) IVUS MLA ≤6.0 mm2, or iii) FFR ≤0.80  Syntax score ≤32  Clinical and anatomic eligibility for both PCI and CABG as agreed to by the local Heart Team  Prior CABG or LM PCI anytime  Prior non-LM PCI within 1 year  Need for cardiac surgery other than CABG  Inability to tolerate DAPT for 1 year  CK-MB >ULN
  • 36. Protocol Procedures PCI recommendations • Complete revasc of all ischemic territories with EES • Provisional LM bifurcation treatment preferred • IVUS guidance strongly recommended • DAPT pre-loading and treatment for ≥1 year • Routine angiographic follow-up not permitted CABG recommendations • Performed w/ or w/o CPB per operator discretion • Complete anatomic revascularization of all vessels ≥1.5 mm in diameter with ≥50% DS • Arterial grafts strongly recommended • Epi-aortic ultrasound and TEE recommended • Clopidogrel use during FU allowed but not mandatory Guideline-directed medical therapy for both groups
  • 37. Results  At 5 years, a primary outcome event had occurred in 22.0% of the patients in the PCI group and in 19.2% of the patients in the CABG group (difference, 2.8 percentage points; 95% confidence interval [CI], −0.9 to 6.5; P = 0.13).  Death from any cause occurred more frequently in the PCI group than in the CABG group (in 13.0% vs. 9.9%; difference, 3.1 percentage points; 95% CI, 0.2 to 6.1).  In the PCI and CABG groups, the incidences of definite cardiovascular death (5.0% and 4.5%, respectively; difference, 0.5 percentage points; 95% CI, −1.4 to 2.5) and myocardial infarction (10.6% and 9.1%; difference, 1.4 percentage points; 95% CI, −1.3 to 4.2) were not significantly different.
  • 38.  All cerebrovascular events were less frequent after PCI than after CABG (3.3% vs. 5.2%; difference, −1.9 percentage points; 95% CI, −3.8 to 0), although the incidence of stroke was not significantly different between the two groups (2.9% and 3.7%; difference, −0.8 percentage points; 95% CI, −2.4 to 0.9).  Ischemia-driven revascularization was more frequent after PCI than after CABG (16.9% vs. 10.0%; difference, 6.9 percentage points; 95% CI, 3.7 to 10.0).
  • 39. • PCI with 2nd generation DES (Xience) was noninferior to CABG for clinical outcomes at 3 years following revascularization of unprotected left main lesions • Adverse clinical events were not uniformly distributed from a temporal standpoint; hazard was highest with CABG vs. PCI in the first 30 days. Between 30 days- 3 years, outcomes were inferior with PCI vs. CABG CABG (n = 957) EES PCI (n = 948) EXCEL Results at 3Yrs • Primary endpoint: Death/MI/stroke: PCI vs. CABG: 15.4% vs. 14.7%, pnon-inferiority = 0.018; psuperiority = 0.98 • Death/stroke/MI at 30 days: 4.9% vs. 7.9%, p = 0.008; Between 30 days-3 years: 11.5% vs. 7.9%, p = 0.02 • 3-year stent thrombosis/graft occlusion: 0.7% vs. 5.4%, p < 0.001; revascularization: 12.6% vs. 7.5%, p < 0.0001 Results Conclusions Stone GW, et al. N Engl J Med 2016;375:2223-5 Primary endpoint pnoninferiority = 0.018 psuperiority = 0.98 %
  • 41.
  • 42. Conclusion  In the EXCEL trial, treatment of patients with LMCAD and visually-assessed low or intermediate SYNTAX scores with CoCr- EES resulted in similar rates of the clinically meaningful composite outcome of death, stroke or MI at 5 years.  The early benefits of PCI due to reduced peri-procedural risk were attenuated by the greater number of events occurring during follow-up, such that at 5 years the cumulative mean time free from adverse events was similar with both treatments
  • 43. • The 3-year primary outcomes are confirmed at 5-years. • PCI showed to have better outcomes in the initial period • After 36 months, there is an inversion of the curves showing better outcomes in the CABG group. • CABG was associated with a reduced risk of ID-TVR when compared to PCI.
  • 44. A P R O SP E C T I VE , R A N D O M I ZE D , O P E N - L A B E L , N O N - I N F E R I O R I T Y T R I A L , C A R R I E D O U T A T 3 6 H O SP I T A L S I N L A T VI A , E ST O N I A , L I T H U A N I A , G E R M A N Y , N O R W A Y , SW E D E N , F I N L A N D , U N I T E D K I N G D O M , A N D D E N M A R K E N R O L L M E N T : D E C E M B E R 2 0 0 8 T O J A N U A R Y 2 0 15 NOBLE Trial
  • 45.  Inclusion Criteria  Stable angina, unstable angina, or acute coronary syndrome  A significant left main lesion  Visually assessed stenosis diameter >50% or fractional flow reserve ≤0.80  Located in the ostium, mid-shaft, or bifurcation  No more than three additional non- complex lesions  Local interventional cardiologists and cardiac surgeons determined that equivalent revascularization could be achieved with CABG or PCI  Exclusion Criteria  Additional non left main complex lesions • Chronic total occlusions • Bifurcation lesions requiring two stent techniques • Calcified or tortuous vessel morphology  ST-elevation infarction within 24 h  Being considered too high-risk for CABG or PCI  Expected survival of less than 1 year
  • 46. Primary Endpoint  A composite of major adverse cardiac and cerebrovascular events (MACCE)  Death from any cause  Non-procedural myocardial infarction  Repeat revascularization  Stroke
  • 47.  The NOBLE trial included 1,201 patients randomly assigned to PCI with biolimus- eluting or sirolimus- eluting stents or to CABG surgery.  In Kaplan–Meier analyses at 5 years, MACCE rates were significantly increased with PCI compared with CABG surgery (29% versus 19%; P = 0.0066), and the noninferiority hypothesis was not met.  Mortality was similar in both groups, but CABG surgery was associated with significant reductions in nonprocedural myocardial infarction, stroke, and repeat revascularization.  Procedural myocardial infarction was not assessed in this trial, and the stent thrombosis rate was substantially higher than in the EXCEL trial, probably reflecting the different stent types used in each trial.  In addition, an inexplicably high rate of late stroke in the PCI group contributed to the increased risk of MACCE associated with this procedure in the NOBLE trial
  • 48. Results Primary endpoint: MACCE HR 1·48 (1·11–1·96); p=0·0066 28·9% 19·1% PCI did not show non-inferiority and CABG was superior to PCI
  • 49. Results All-cause mortality 11.5% 9.5% HR 1·07 (0·67–1·72); p=0·77 11·6% 9·5%
  • 50. Results Non-procedural myocardial infarction HR 2·88 (1·40–5·90); p=0·004 6·9% 1·9%
  • 51. Results Total repeat revascularization HR 1·50 (1·04–2·17); p=0·03 10·4% 16·2%
  • 53. PCI CABG P–value Definite ST or symptomatic graft occlusion* 3%(9) 4%(15) 0·22 Procedural myocardial infarction (post hoc) 5%(16/296) 7%(16/238) 0·52 Results Secondary endpoints *Kaplan-Meier 5 year estimates by intention-to-treat
  • 54. PCI CABG P–value Repeat revascularization 16%(71) 10%(47) 0·032 Target lesion revascularization 12%(50) 8%(36) 0·14 De novo lesion revascularization 6%(24) 3%(11) 0·018 Target LMCA revascularization 10%(41) 9%(33) 0·37 Results Secondary endpoints Kaplan-Meier 5 year estimates by intention-to-treat
  • 55. Kaplan-Meier 5 year estimates by intention-to-treat 4.9% 1.9% K-M estimates
  • 56. Results SYNTAX score subgroups 4.9% 1.9% K-M estimates HR 1·88 (1·23–2·89); p=0·0031 HR 1·16 (0·76–1·78); p=0·48 HR 1·41 (0·62–3·20); p=0·41 SYNTAX score assessed by independent corelab (CERC)
  • 57. Conclusions PCI did not meet non-inferiority for the primary endpoint of 5-year MACCE compared to CABG CABG was superior to PCI PCI resulted in higher rates of non-procedural myocardial infarctions Repeat revascularization was higher after PCI, primarily due to de novo lesions and non LMCA target lesion revascularization All-cause mortality was similar for PCI and CABG
  • 58.
  • 59. IRIS-MAIN REGISTRY SECULAR TRENDS IN LMCA DISEASE: RESULTS FROM THE IRIS-MAIN REGISTRY
  • 60. IRIS-MAIN REGISTRY  A nonrandomized, multinational, multicenter observational study  Patients were recruited from 50 academic and community hospitals in Asia (China, India, Indonesia, Japan, Malaysia, South Korea, Taiwan, and Thailand)
  • 61. OBJECTIVE METHODS  To evaluate patient characteristics and long- term outcomes for the treatment of LMCA disease over time in “real-world” clinical practice  Authors analysed data from a large “all-comers” registry that includes patients who received medical therapy, PCI, or CABG for unprotected LMCA disease.
  • 62. STUDY POPULATION  Study population was a part of IRIS-MAIN registry  5,833 with significant LMCA disease were identified between January 1995 and December 2013 at 50 participating sites  616, 2,866 & 2,351 were treated with Medical therapy alone, PCI & CABG respectively  Patients who had prior CABG and those who underwent concomitant valvular or aortic surgery were excluded
  • 63.  For the analyses, 3 historical time periods were chosen on the basis of the generation of stent used in PCI: wave 1 (BMS) for 1995 to 2002; wave 2 (first generation DES) for 2003 to 2006; and wave 3 (second-generation DES) for 2007 to 2013.
  • 64. Results: Trends of patient characteristics and treatments  Over time, the proportion of patients treated with PCI rather than CABG increased substantially, whereas the proportion of patients who received medical therapy remained steady  During the study period, there was an increase of age for all 3 treatments, and more patients tended to present with stable angina.  Among the patients who underwent coronary revascularization, there was an increased risk of patient comorbidities and anatomic complexity over time.
  • 65.  Improved chronic pharmacotherapy was found for all treatment groups, particularly in terms of greater use of antiplatelet agents and statins.  In the PCI group, the type of stents used dramatically changed, and the number and length of stents significantly increased with increasing disease complexities.  Despite an increased proportion of patients with distal bifurcation involvement, more patients were treated with the simple 1-stent crossover technique.
  • 66.  In the CABG group, over time, off-pump surgery was more frequently performed, and the total number of grafts has decreased.  Grafting using the internal mammary artery was more frequently performed, but adoption rates varied for the radial artery.
  • 67. Follow Up  Median follow-up time was 9.7 years, 5.6 years, and 3.0 years for patients treated in waves 1, 2, and 3, respectively
  • 68. Patient Characteristics Over Time in Each Treatment Stratum
  • 69. Patient Characteristics Over Time in Each Treatment Stratum
  • 70. OUTCOMES  Clinical outcomes of interest were  All-cause death  Serious composite outcome (death, MI, or stroke)  Repeat revascularization  Major adverse cardiac and cerebrovascular events (MACCE)[defined as the composite of death, MI, stroke, and repeat revascularization]
  • 71. Trends in Medications and Procedural and Surgical Characteristics Over Time in Each Treatment Stratum
  • 72. Results  Medical therapy group:  Adjusted risks for mortality; composite of death, MI, or stroke; and MACCE gradually decreased over time  PCI group:  Trends toward decreasing risks for mortality, composite outcomes, and repeat revascularization were also statistically significant.  CABG group:  Risks for any clinical outcomes remained relatively stable, with exception of decreasing risk of repeat revascularization
  • 73. Risk-Adjusted Trends of Hazard Ratios for Clinical Outcomes Over Time in Each Treatment Stratum
  • 74. Risk-Adjusted Trends of Hazard Ratios for Clinical Outcomes Over Time in Each Treatment Stratum
  • 75. Results  During all time periods Medically treated patients had an extremely higher rate of mortality and composite of death, MI, or stroke than those who received PCI or CABG.  Risks of mortality and composite of death, MI, or stroke were comparable between PCI and CABG  Risks of repeat revascularization and MACCE were higher in PCI than CABG group  Adjusted hazard ratios for risks of all clinical outcomes after PCI relative to CABG gradually decreased over time  This suggest that gap in treatment effect between PCI and CABG has been narrowed.
  • 76. Risk-Adjusted HRs of Relative Clinical Outcomes Between Treatment Strategies Over Time
  • 77. Risk-Adjusted HRs of Relative Clinical Outcomes Between Treatment Strategies Over Time
  • 78. Secular Changes of Treatment Effect and Guideline Recommendations in Relation to Medical Advances of Each Treatment Stratum for Left Main Coronary Artery Disease
  • 79. CONCLUSIONS  Patient risk profiles and treatment of medical and revascularization therapy have evolved remarkably over time among patients with unprotected LMCA disease  Gap in treatment effect between PCI and CABG has progressively diminished, mainly due to more improved outcomes with PCI.
  • 80. Revascularization for Unprotected Left MAIN Coronary Artery Stenosis: COMparison of Percutaneous Coronary Angioplasty versus Surgical REvascularization from Multi-Center Registry ( K O R E A N R E G I ST R Y ) The MAIN-COMPARE Study
  • 81. Study Population  Consecutive patients with unprotected left main coronary disease who received stenting and underwent CABG between January 2000 and June 2006.  From the second quarter of 2003 (May 2003), DES have been exclusively used as treatment device for PCI at participating centers.
  • 82. January, 2000 Second quarter, 2003 June, 2006 Wave I BMS CABG Wave II DES CABG MAIN-COMPARE Registry Stenting (BMS vs. DES) vs. CABG Unprotected LMCA disease Unprotected LMCA disease Study Design
  • 83. Inclusion Criteria Exclusion Criteria  Patients with unprotected left main disease (defined as stenosis of more than 50%) who underwent stenting or isolated CABG.  Primary End Point  Death  Composite of death, Q-wave myocardial infarction, or stroke  Target-vessel revascularization • Prior CABG • Concomitant valvular or aortic surgery • ST-elevation MI • Cardiogenic shock at presentation
  • 84. January, 2000 Second quarter (May), 2003 June, 2006 Wave I LMCA disease BMS (N=318) CABG (N=448) Wave II LMCA disease DES (N=784) CABG (N=690) MAIN-COMPARE Study Stenting (BMS or DES) vs. CABG PCI (N=1102) CABG(N=1138)Total (N=2240)
  • 85. Asan Medical Center PCI patients (N=1102) Reason for PCI 4Without suitable bypass conduits 12Concurrent severe medical illness 2Current malignancy 3Limited life expectancy 8Age ≥ 80 years and poor performance status 1073 (97%) Physician’s preference -”good candidate for stenting or CABG” Patient’s preference/ Patient refused surgery -“poor candidate for stenting” 29 (3%)Physician refused surgery -“poor candidates for CABG”
  • 86. Asan Medical Center Angiographic Characteristics Variable Stents (n=1102) CABG (n=1138) P Value Involved location 0.04 Ostium and/or mid-shaft 50.6 46.2 Distal bifurcation 49.4 53.8 Extent of diseased vessel <0.001 Left main only 25.2 6.2 Left main plus single-vessel disease 24.0 10.5 Left main plus double-vessel disease 26.0 26.3 Left main plus triple-vessel disease 24.8 57.0 Right coronary artery disease 35.9 70.7 <0.001 Restenotic lesion 2.9 1.2 0.005
  • 87. DEATH (Overall PCI and CABG matched cohort: 542 pairs)
  • 88. Death, Q-MI, or Stroke : Overall
  • 90. Asan Medical Center Hazard Ratios for Clinical Outcomes (Overall PCI and CABG matched cohort: 542 pairs) Overall Patients (N=542 pairs) Outcome Hazard Ratio* (95% CI) P value Death 1.18 (0.77-1.80) 0.45 Composite outcome (death, Q-wave myocardial infarction, or stroke) 1.10 (0.75-1.62) 0.61 Target-vessel revascularization 4.76 (2.80-8.11) <0.001 *HR are for the stenting group, as compared with CABG group
  • 91. (BMS and contemporary CABG matched cohort: 207pairs) Death: BMS and contemporary CABG matched cohort: 207pairs
  • 92. Death, Q-MI, or Stroke BMS and contemporary CABG matched cohort: 207pairs
  • 93. Target-vessel revascularization BMS and contemporary CABG matched cohort: 207pairs
  • 94. Asan Medical Center Hazard Ratios for Clinical Outcomes Wave 1 (N=207 pairs) Outcome Hazard Ratio* (95% CI) P value Death 1.04 (0.59-1.83) 0.90 Composite outcome (death, Q-wave myocardial infarction, or stroke) 0.86 (0.50-1.49) 0.59 Target-vessel revascularization 10.70 (3.80-29.90) <0.001 *HR are for the stenting group, as compared with CABG group (BMS and contemporary CABG matched cohort: 207pairs)
  • 95. DEATH: DES and contemporary CABG matched cohort: 396 pairs
  • 96. Death, Q-MI, or Stroke DES and contemporary CABG matched cohort: 396 pairs
  • 97. Target-vessel revascularization DES and contemporary CABG matched cohort: 396 pairs
  • 98. Asan Medical Center Hazard Ratios for Clinical Outcomes Wave 2 (N=396 pairs) Outcome Hazard Ratio* (95% CI) P value Death 1.36 (0.80-2.30) 0.26 Composite outcome (death, Q-wave myocardial infarction, or stroke) 1.40 (0.88-2.22) 0.15 Target-vessel revascularization 5.96 (2.51-14.10) <0.001 *HR are for the stenting group, as compared with CABG group (DES and contemporary CABG matched cohort: 396 pairs)
  • 99. Conclusion  In a cohort of patients with unprotected left main coronary artery disease, we found no statistical significant difference in the risk of death and serious composite outcomes (death, Q-wave myocardial infarction, or stroke) between patients receiving stenting and those undergoing CABG.  These results were consistent when comparing bare-metal stents or drug- eluting stents with concurrent CABG controls, although a statistically nonsignificant trend was noted toward higher risk in the analysis for drug- eluting stents.  However, the rate of target-vessel revascularization was significantly lower in the CABG group than in the PCI group, regardless of stent type.
  • 100. Changes in PCI Guideline Recommendations for LMCA Disease
  • 101. Changes in PCI Guideline Recommendations for LMCA Disease
  • 102. Changes in PCI Guideline Recommendations for LMCA Disease
  • 103. Recommendation for the type of revascularization in patients with Left main CAD Neumann FJ et al., European Heart Journal (2019) 40, 87–165