Transcript Randomized Comparison of Percutaneous Coronary Intervention with Sirolimus-Eluting Stents versus Coronary Artery Bypass Grafting in Unprotected Left Main Stem Stenosis E.

Randomized Comparison of Percutaneous
Coronary Intervention with Sirolimus-Eluting
Stents versus Coronary Artery Bypass Grafting
in Unprotected Left Main Stem Stenosis
E. Boudriot*, H.Thiele*, T.Walther, C.Liebetrau,
P.Boeckstegers, T.Pohl, B.Reichart, H.Mudra, F.Beier, B.
Gansera, F.J.Neumann, M.Gick, T. Zietak, S. Desch,
G.Schuler, F.W.Mohr
* Both authors contributed equally
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Disclosures: supported in part by Deutsche Stiftung für Herzforschung
Study
Prospective randomized trial
CABG (arterial grafts) versus PCI + Sirolimus-Eluting Stent
in left main stem stenosis
• Primary combined endpoint within 12 months
- Mortality
- Myocardial infarction
- Target vessel revascularization (TVR)
 Secondary endpoints
- Individual clinical endpoints
- Periinterventional complications
- CCS-classification
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1)
low output syndrome (intravenous catecholamines and/or
IABP)
2) Congestive heart failure requiring hospital admission
3) cerebrovascular events (stroke, coma, TIA, PRIND)
4) pericardial tamponade
5) arrhythmia (ventricular fibrillation, VT, A. fibrillation)
6) major bleeding requiring blood transfusion
7) re-thoracotomy for bleeding
8) renal failure requiring dialysis
9) major infections compromising post-procedural rehabilitation
10) vascular access site complications requiring surgery
11) Sternum instability requiring additional treatment
Study Centers
Universität München - Großhadern
Klinikum Neuperlach München
Herzzentrum Bad Krozingen
Herzzentrum Leipzig
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Statistics – Sample Size
Zone of non-inferiority
Limit of equivalence (10.0%)
90% CI
Inferior
Inferior
-15.0
-10.0
-5.0
Stenting better
0
5.0
10.0
15.0
CABG better
Difference in MACE rates
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Assumed event rates: CABG: 15%, DES: 12.5%
Difference in MACE rates of 2.5%  2 x 100 patients to show non-inferiority
Study Flow Chart
430 Patients with Unprotected Left Main Disease
229 Non-Eligible
179 CABG
201 Eligible
100 Assigned to PCI
101 Assigned to CABG
3 Converted to
CABG
5 No
Angiographic
Follow-up
0 Lost to
Follow-up
100 Included in Primary
Analysis
100 Included in Secondary
Analysis
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20 No
Angiographic
Follow-up
1 Lost to
Follow-up
100 Included in Primary
Analysis
100 Included in Secondary
Analysis
22 Infarction < 48 Hours
11 Cardiogenic Shock
8 Chronic Total Occlusion
65 Lesion Length > 30 mm
6 Non-CABG Suitable
14 Prior Cardiac Surgery
36 Age > 80 Years
21 Malignancy
27 Combined Cardiac Surgery
19 Dominant Left Circumflex
40 PCI
10 Conservative
Patient Characteristics
Variable
PCI *
(n=100)
CABG
(n=101)
P Value
Age (y), median (IQR)
66 (62;73)
69 (63;73)
0.24
Men, No. (%)
72 (72)
78 (77)
0.49
Body-mass-index (kg/m2), median (IQR)
27.2 (24.6;31.5)
27.0 (24.9;30.1)
0.31
Cardiovascular risk factors, No. (%)
Current smoking, No. (%)
Hypertension, No. (%)
Hypercholesterolemia, No. (%)
Diabetes mellitus, No. (%)
35 (35)
82 (82)
68 (68)
40 (40)
28 (28)
83 (82)
65 (64)
33 (33)
0.34
0.88
0.89
0.35
19 (19)
17 (17)
2 (2)
14 (14)
10 (10)
4 (4)
0.43
Previous stroke, No. (%)
3 (3)
6 (6)
0.51
Baseline creatinine, median (IQR), mol/l
86.0 (76.5;100.0)
86.0 (75.0;97.0)
0.52
Left ventricular ejection fraction (%), median (IQR)
65.0 (55.0;70.0)
65.0 (55.0;68.0)
0.88
Logistic EuroSCORE, median (IQR)
2.4 (1.5;3.7)
2.6 (1.7;4.9)
0.08
Discharge medication, No. (%)
Aspirin, No. (%)
Clopidogrel, No. (%)
Beta-blocker, No. (%)
ACE-inhibitor‡/AT-1-ant.§, No. (%)
Statins, No. (%)
100 (100)
100 (100)
99 (99)
98 (98)
97 (97)
101 (100)
32 (32)
96 (95)
93 (92)
95 (94)
0.99
<0.001
0.22
0.11
0.51
Previous myocardial infarction, No. (%)
Q wave infarction, No. (%)
Non-Q wave infarction, No. (%)
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Angiographic Characteristics
Variable
Lesion type, No. (%)
Ostial, No. (%)
Trunk, No. (%)
Distal, No. (%)
PCI
(n=100)
CABG
(n=101)
0.72
20 (20)
6 (6)
74 (74)
23 (23)
8 (8)
70 (69)
Isolated left main, No. (%)
Left main + 1-vessel disease, No. (%)
Left main + 2-vessel disease, No. (%)
Left main + 3-vessel disease, No. (%)
28 (28)
35 (35)
26 (26)
11 (11)
29 (29)
27 (27)
28 (28)
17 (17)
PCI technique for distal left main
T-Stenting, No. (%)
Provisional T-stenting, No. (%)
Crush-Stenting, No. (%)
V-Stenting, No. (%)
40 (40)
30 (30)
3 (3)
1 (1)
-
-
100 (99)
55 (54)
37 (37)
35 (35)
24.0 (19.0;29.0)
23.0 (14.8;28.0)
CABG, conduits per patient
Left internal mammary artery, No. (%)
Right internal mammary artery, No. (%)
Radial artery, No. (%)
Venous graft, No. (%)
SYNTAX score, median (IQR)
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P Value
0.49
0.09
Type of Left Main Stenosis
PCI
20%
CABG
Ostium
23%
6%
Body
8%
74%
Distal
70%
p = 0.72
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Periinterventional Complications
Stenting
(n=100)
CABG
(n=101)
Major bleeding
CV accident
A. fibrillation
Access site complication
Re-thoracotomy
Major infection
Renal failure + dialysis
Critical illness PNP
CHF with readmission
Pericardial tamponade
3 (3%)
1 (1%)
-
2 (2%)
2 (2%)
19 (19%)
2 (2%)
5 (5%)
1 (1%)
1 (1%)
-
Any complication
4 (4%)
30 (30%)
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p
-
<0.001
Change in CCS-Classification
3
CCS-Class
0.5
0.0 (IQR 0.0;1.0)
1
0.0 (IQR 0.0;1.0)
1.5
p=0.67
2.0 (IQR 2.0;4.0)
2
3.0 (IQR 2.0;4.0)
2.5
p=0.19
p<0.001
p<0.001
0
Baseline
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12 Months
PCI
CABG
Primary Endpoint – MACE 12 Months
PCI
(n=100)
CABG
2 (2.0%)
3 (3.0%)
5 (5.0%)
3 (3.0%)
-8.2 to 2.9
-5.8 to 5.9
<0.001
0.002
3 (3.0%)
-
3 (3.0%)
-
-5.8 to 5.9
0.002
Death + AMI
Repeat revasc.
5 (5.0%)
14 (14.0%)
8 (7.9%)
6 (5.9%)
-10.6 to 4.4
-0.3 to 17.1
<0.001
0.35
<30 days
day 30-12 m.
1 (1.0%)
13 (13.0%)
2 (2.0%)
4 (4.0%)
-6.1 to 3.7
-1.3 to 17.6
<0.001
0.45
19 (19.0%)
14 (13.9%)
-5.3 to 15.7 0.19
Death
AMI
<30 days
day 30-12 m.
Any MACE
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95% CI
(n=101)
p-Value
Non-inferiority
MACE 12 Month
PCI
CABG
p value for non-inferiority
30
p = 0.19
25
p = 0.35
20
14
15
10
5
19
14
p < 0.001
5
2
p = 0.02
3
6
3
0
Death
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MI
TVR
MACE
Primary Endpoint – MACE 12 Months
Intention to treat
Limit of equivalence
-9.4
-3.0
2.7
Death
-5.8
AMI
0
<0.001
5.9
0.002
-0.3
Repeat revascularization
17.1
8.1
0.35
5.1
-5.3
15.7
0.19
MACE
-15.0
-10.0
-5.0
PCI better
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0
5.0
10.0
CABG better
15.0
MACE Mid-term Follow-up
Cumulative major adverse cardiac
event free survival (%)
Median follow-up 36.5 months
100
CABG
80
PCI
60
40
Log-rank: p = 0.13
20
0
300
600
900
1200
1500
Days after randomization
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1800
Death and MI – Mid-term Follow-up
Median follow-up 36.5 months
PCI
Cumulative death and MI
event free survival (%)
100
CABG
80
60
Log-rank: p = 0.97
40
20
0
300
600
900
1200
1500
Days after randomization
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1800
TVR - Mid-term Follow-up
Cumulative major adverse cardiac
event free survival (%)
Median follow-up 36.5 months
CABG
100
80
PCI
Log-rank: p = 0.03
60
40
20
0
300
600
900
1200
1500
Days after randomization
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1800
Summary
• In patients with unprotected left main stenosis
PCI using DES failed to show non-inferiority to
CABG.
• The inferiority for PCI is driven by the higher
repeat revascularization rate.
• For death and MI the results in both groups
are comparable.
• Both treatment strategies effectively reduce
symptoms.
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Conclusions
In highly-experienced centers the decision making
process on how to treat unprotected left main
disease should therefore be based on an
interdisciplinary approach taking into account the
- individual success,
- periprocedural risk
- bypass graft occlusion risk
- potential restenosis rate
based on the morphology of the underlying lesion
and patient comorbidities.
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