Unprotected Left Main Intervention: EXCEL Trial Samin K. Sharma, MD, FACC, FSCAI Director, Clinical and Interventional Cardiology Zena & Michael Wiener Professor of Medicine President Mount Sinai Heart Network Dean International Clinical Affiliation Mount Sinai Heart , New York Disclosure/COI: Speaker Bureau for Abbott, BSC, DSI, TMC, Abiomed
Complexity of PCI-treated Patients has Historically Increased with Time
Complexity
Left Main Three Vessels-DM CTO >1 Bifurcation Two Vessels Small Vessels Long Lesions Single Vessel Time
CABG PCI
Today
Appropriateness Criteria: Method of Revascularization of Advanced CAD CABG
PCI
No diabetes & normal LVEF
Diabetes
Depressed LVEF
No diabetes & normal LVEF
Diabetes
Depressed LVEF
Two Vessel Coronary Disease+ Proximal LAD Stenosis
A A
A A
A A
A A
A A
Three Vessel Coronary Disease
A A
A A
A A
A A U U
UU
U U
A
A A
A A
A A
A A
A A
I I
I I
II I
Isolated Left Main stenosis Isolated Left Main and additional Coronary artery disease
Patel MR et al. J Am Coll Cardiol. 2009;53(6):530-553
EXCEL Trial (Evaluation of Xience Prime vs CABG for Examination of LM Disease) LM disease (±1, 2 or 3 vessel disease) and a SYNTAX score of ≤32 Randomize 2600 pts
XIENCE® V/Prime stent ®ABBOTT Vascular
CABG
• The primary endpoint is the composite incidence of death, MI or stroke at a median FU duration of 3 years, powered for sequential non-inferiority and superiority testing. • The major secondary endpoint is the composite incidence of death, MI, stroke or unplanned repeat revascularization. All patients will be followed for 5 years total.
LMCA Stenosis Location
LMCA
D LA
26% Ostium
X C L 66% Bifurcation
8% Body-Shaft
About two third of LMCA Lesions include distal bifurcation
Issues in PCI (DES) of ULMCA Stenosis • Procedural
success
• Acute complications / stent thrombosis • Restenosis / TLR • Sudden death • Long-term follow-up vs. CABG
Meta-analysis of PCI of Unprotected LMCA BMS Clinical Setting MI/UA
F/U
(mths)
Cardiac death (%)
Restenosi s (%)
MACE (%)
107
91 / 16
15±8
10.6
22
30/80
1998
42
All elective
10±5
0
22
19
Karam et al.
1998
39
36 / 3
24±7
15.4
5
20
Kosuga et al.
1999
107
83 / 24
35
11.2
40
22
Wong et al.
1999
55
All elective
16±10
1.8
20
18
Silvestri et al.
2000
140
All elective
12
8.7
23
28
Kosuga et al.
2001
101
86 / 15
34
5.9
20
38
Lee et al.
2001
13
All elective
18±3
7.7
23
38
Park et al.
2001
127
All elective
12±11
0.9
12
13
Tan et al.
2001
279
Various
19
20.2
25
35
Takagi et al.
2002
67
Various
31±23
11.9
24
34
Sharma et al.
2002
200
Various
15±8
6
12
18
16 ±12
9.1
22
26
Author
Year
N
ULTIMA (Ellis)
1997
Park et al.
Total
1077
DES for the Unprotected LMCA Park
Chieffo
Valgimigli
Lee
Price
Migliorini
Erglis
(1)
(2)
(3)
(4)
(5)
(6)
(7)
Patients (n)
102
85
95
50
50
101
53
Distal location (%)
71
81
65
60
94
87
81
0
3.5
11
4
2
11
2
84.3
NR
NR
42
98
96
100
Angiographic resten (%)
7*
19*
NR
NR
44‥
16*
6*
TLR or TVR (%)
2
18.8
6.3
13
38
14
2
Cardiac mortality12 m(%) Angiographic F/U (%)
3. Circulation 4.4% & TLR2005;111:1383; of 11.2% 4. JACC 2006;47:864; 5. JACC 2006;47:871; 6. CCI 2006;68:225; 7. JACC 2007;50:491 (half of the BMS trials) 1.
JACC 2005;45:351;
2. Average Circulation 2005;111:791; Mortality
DES in Non-Bifurcation Unprotected LMCA MACE at Hospitalization and at Long-Term Clinical FU (N = 147)
Event-Free at 1400 days
In-Hospital (N = 147) CI 92.6%
Cardiac death (%)
Follow-Up (886±308 D)
0
2.7
89%
Death in 60 high-risk pts (%)
0
6.6
CI
Death in 87 low-risk pts (%)
0
0
TLR (%)
0.7
0.7
TVR (%)
0.7
4.7
MACE (%)
4.0
7.4
886 Days
MACE at 886±308 days occurred in 11 pts (7.4%);the dashed lines represent the 95% CIs
High-risk pts were defined as EuroSCORE ≥6 and/or Parsonet ≥13 and/or prior bypass surgery with failure of all conduits. Chieffo et al, Circulation 2007;116:158.
A Randomized Comparison of PES vs. BMS for Treatment of Unprotected LMCA Stenosis 6-Months Cumulative Outcomes: All had CB and IVUS BMS (n = 50) PES (n = 53) P Value Total death (%)
2
2
>0.99
MI (%)
14
9
0.548
TLR (%)
16
2
0.014
MACE (%)
30
13
0.054
Angiographic resteno (%)
22
6
0.021
IVUS neointimal volume (mm3)
26 ± 22
17 ± 17
0.014
Erglis et al. J Am Coll Cardiol 2007;50:491
PCI (DES) vs. CABG for ULMCA Lesion • Observational Data: - Main-Compare by Park - Cedars-Sinai data by Lee - Multicenter data by Chieffo - Bolognese registry data
• Randomized Trials - LE MANS Trial - SYNTAX Trial (LM subset) - PRECOMBAT Trial
PCI vs. CABG for ULM Disease: Bologna Registry Clinical Outcomes at Median FU of 430 days CABG (n=154) PCI (n=157)
30
25.5
25
20
P = NS
30
P = 0.0001
DES (n=94)
25
P = NS
20
%
% 15
12.3
13.4
15
0
10
8.3
10
4.5
5
Mortality
12.5
11.7
MI
5.3 2.6 TLR
5
0
Mortality
MI
TLR
Palmerini et al. Am J Cardiol 2006;98:54
MAIN-COMPARE Registry: Stents versus CABG for Left Main Coronary Artery Disease KMDEATH Curves for LM Matched for Propensity Scores for DES or CABG DEATH, Q-wave MI or STROKE (N= 396 pairs) 96.9 95.9 93.1 94.9 95.9
93.6
94.9
91.0 DES CABG
P = 0.26
P = 0.26
TVR
93.9 91.7
92.0 88.5
DES CABG
P = 0.16
P = 0.16
99.5
98.4
98.4
93.8
92.3
90.7
P <0.0001 DES CABG
Seung et al. New Engl J Med 2008;358:1781
LE MANS Trial 1-Yr Outcomes After PCI vs. CABG for ULM Intervention PCI (n=52)
CABG (n=59)
P
2
13
0.03
1- yr MACCE-Free Survival (%)
71.2
75.5
0.29
In-stent restenosis (%)
9.6
-
-
Stent thrombosis (%)
0
-
-
Change in LVEF (%)
3.3 ± 6.7
0.5 ± 0.8
0.047
Outcome
30-day MACCE (%)
Kahn et al. J Am Coll Cardiol 2008
PRECOMBAT Trial: DES vs. CABG ULMCA Disease Cumulative Incidence of the Primary End Point of MACE or CVA
Cumulative Incidence of Death from Any Cause, MI, or Stroke
Park S published online at NEJM.org April 4, 2011
PRECOMBAT Trial: DES vs. CABG ULMCA Disease
Clinical End Points 24 Mo after Randomization 18
PCI n=300 CABG n=300
16
p=0.12 14 12
12.2
p=0.02
% 10 8
8.1
p=0.45
6
4.4 4.7
4
3.4 2.4
2 0
9.0
p=0.83
MACE
Death/ MI/ Death Stroke
p=0.49
4.2
p=0.25
p=0.56 1.7
MI
1.0
1.4
0.4 0.7
Stroke
0.3
TVR
ST
Park S published online at NEJM.org April 4, 2011
SYNTAX Trial Eligible Patients
Syntax Objective: To compare the MACCE rate at 12 months between patients treated with TAXUS速 stents vs. patients undergoing CABG for de novo 3VD and/or LM disease. (*MACCE = major adverse cardiac and cerebrovascular events; defined as death, stroke, MI, or repeat revascularization)
De novo disease Isolated left main Limited Exclusion Criteria Previous interventions (PCI or CABG) Acute MI with CPK>2x Concomitant valve surgery
left main + 1-vessel disease left main + 2-vessel disease
3-vessel disease Revascularization in all 3 vascular territories
left main + 3-vessel disease Serruys P et al. NEJM 2009;360:961.
SYNTAX Trial: Left Main and 3 V CAD Subgroup MACCE Rates at 12 Months
25
20
CABG Taxus
19.8
15.8 15
13.7
13.2
% 10
14.4
8.5
7.1
19.3
19.2
15.4 11.5
7.5
5
0
All LM N=705
LM Isolated N=91
LM+1VD N=138
LM+2VD N=218
LM+3VD N=258
3VD ( w/o LM) N=1095
Serruys PW et al. N Engl J Med 2009;360:961-72.
• SYNTAX score is purely an anatomic score of the extent of CAD (>50%) in a pt • Each lesion is assigned a numerical number and then sum of all lesions score for a patient is calculated to come up with the final numerical SYNTAX score • Pt are divided in 3 groups: Low <22 Intermediate 23-32
High >32 Serruys P et al. NEJM 2009;360:961.
SYNTAX Trial LM Subgroup:
MACCE in Relation to SYNTAX Score 30
CABG TAXUS
P = .008 25.3
MACCE at 12 Months (%)
25 20 15
P = .19
P = .54 15.5
13.0
10
12.6
12.9
7.7
5 0
N=103
≤22
N=118
N=92
N=195
23-32 SYNTAX Score
N=150 N=135
≥33
Serruys PW et al. N Engl J Med 2009;360:961-72.
MACCE to 5 Years by SYNTAX Score Tercile LM Subset Low Scores 0-22 CABG (N=104) TAXUS (N=118) Cumulative Event Rate (%)
LM Disease 50
CABG
PCI
P
Death
11.3%
7.0%
0.28
CVA
4.1%
1.8%
0.28
MI
3.1%
6.2%
0.32
Death, CVA or 15.2% MI
13.9%
0.71
Revasc 20.3%
23.0%
0.65
P=0.74 31.5% 30.4%
25
0 0
12
24
36
48
Months Since Allocation
60
MACCE to 5 Years by SYNTAX Score Tercile LM Subset Intermediate Scores 23-32 CABG (N=92) TAXUS (N=103) LM Disease Cumulative Event Rate (%)
50
CABG
PCI
P
Death
19.3%
8.9%
0.04
CVA
3.6%
1.0%
0.23
MI
4.6%
6.0%
0.71
Death, CVA or 24.9% 15.7% MI
0.11
Revasc 16.6% 22.2%
0.40
P=0.88 32.7% 32.3%
25
0 0
12
24
36
48
Months Since Allocation
60
MACCE to 5 Years by SYNTAX Score Tercile LM Subset High Scores â&#x2030;Ľ33
CABG (N=149) TAXUS (N=135) LM Disease Cumulative Event Rate (%)
50
29.7% 25
0 12
24
36
Death
PCI
P
14.1% 20.9%
0.11
CVA
4.9%
1.6%
0.13
MI
6.1%
11.7%
0.13
Death, CVA or 22.1% 26.1% MI
0.40
46.5%
P=0.003
0
CABG
48
Months Since Allocation
60
Revasc 11.6% 34.1% <0.001
Clinical Case #2: Complex Intervention for Non-STEMI and Mild Hypotension • 73 yrs old male patient with Non-STEMI and BP 86/60mmHg • History: HTN, NIDMM, Hyperlipidemia, Angina/SOB on exertion with (+) MPS suggestive of LAD ischemia • Medication: ASA, Clopidogrel, Metformin, IV Dopamine • Cath: LVEDP normal, LVEF 25% III vessel CAD LM disease No aortic stenosis • Planned Impella assisted high risk PCI of LM/LAD/LCx using Rotational atherectomy for LAD and CB PTCA for LCx followed by DES and SKS for dLM lesion
Clinical Case #2: Complex Intervention for Non-STEMI and Mild Hypotension • 73 yrs old male patient with Non-STEMI and BP 86/60mmHg • History: HTN, NIDMM, Hyperlipidemia, Angina/SOB on exertion with (+) MPS suggestive of LAD ischemia • Medication: ASA, Clopidogrel, Metformin, IV Dopamine • Cath: LVEDP normal, LVEF 25% III vessel CAD LM disease No aortic stenosis
• Successful intervention of: RA 1.75mm burr and LMDistal (Xience 3.5/18), LAD-mid (Xience 3/33) and 2.75mm Flextome and then LCx-prox (Xience3/18), LCx-OM2 (Xience 2.75/28)
2011 ACCF/AHA/SCAI Guideline for Coronary Revascularization: Percutaneous Coronary Intervention and Coronary Artery Bypass Surgery JACC. 2011:58;2550. GNL 2011
ACCF/AHA/SCAI Guidelines 2011: UPLM Revascularization to Improve Survival Revasc Method CABG PCI
COR I IIaFor SIHD when low risk of PCI complications and high likelihood of good long-term outcome (e.g., SYNTAX score of ≤22, ostial or trunk left main CAD), and a signficantly increased CABG risk (e.g., STS-predicted risk of operative mortality ≥5%)
LOE B B
IIbFor SIHD when low to intermediate risk of PCI complications and intermediate to high likelihood of good long-term outcome (e.g., SYNTAX score of <33, bifurcation left main CAD) and increased CABG risk (e.g., moderate-severe COPD, disability from prior stroke, prior cardiac surgery, STS-predicted operative mortality >2%)
B
III: HarmFor SIHD in patients (versus performing CABG) with unfavorable anatomy for PCI and who are good candidates for CABG
B
IIaFor UA/NSTEMI if not a CABG candidate IIaFor STEMI when distal coronary flow is <TIMI grade 3 and PCI can be performed more rapidly and safely than CABG
B C
GNL 2011
Method of Revascularization of Multi-vessel and LM Coronary Artery Disease CABG
PCI
Two-vessel CAD with proximal LAD stenosis
A
A
Three Vessel CAD with low CAD burden (i.e., three focal stenosis, low SYNTAX score)
A
A
Three-vessel CAD with intermediate to high CAD burden (i.e., multiple diffuse lesions, CTO, or high SYNTAX score >32)
A
U
Isolated left main stenosis
A
U
Left main stenosis and additional CAD with low CAD burden (i.e., one to two vessel additional involvement, low SYNTAX score <33)
A
U
Left main stenosis and additional CAD with intermediate to high CAD burden (i.e., three vessel involvement, presence of CTO, or high SYNTAX score >32)
A
I
Patel et al., JACC 2012; 59:0000
European Guidelines
ACCF/AHA/SCAI Guidelines for Coronary Revascularization 2011:
Heart Team Approach to UPLM or Complex CAD
GNL 2011
Proposed Approach to LM PCI Sign LCX
Crush or T stenting
Kissing stents
50% Insign or small LCX
Single across LCX Small LM
Single across LCX 4 mm
Large LM
LM Bifurcation Lesion: Two Stent Approach An approach for bifurcation lesions when using 2 stents as intention to treat Bifurcation lesion with no disease proximal to the bifurcation or very short proximal lesion
SKS/VSTENT
Bifurcation lesion with main branch disease extending proximal to the bifurcation and side branch which has origin with about 900 angle
T- STENT Culotte
Bifurcation lesion with main branch disease extending proximal to the bifurcation and side branch which has origin with about 600 angle
SHORTMINI Crush
EXCEL Trial (Evaluation of Xience Prime vs. CABG for Examination of LM Disease) LM disease (±1, 2 or 3 vessel disease) and a SYNTAX score of ≤32 Randomize 2600 pts
ABBOTT Vascular XIENCE Prime stent
CABG
• The primary endpoint is the composite incidence of death, large MI or stroke at a median FU duration of 3 years, powered for sequential non-inferiority and superiority testing. • The major secondary endpoint is the composite incidence of death, MI, stroke or unplanned repeat revascularization. All patients will be followed for 5 years total.
16TH AUNNUAL LIVE SYMPOSIUM June 12-15,2013
Take Home Message:
Techniques of LM Stenting with Circulatory Support Many studies have shown the feasability and safety of LM stenting with DES and MACE outcomes upto 3 yrs remains equal to CABG in the majority Optimal technique, strategy, stent deployment and positioning remain crucial in this setting In many patients a single stent cross-over has shown excellent long-term results