Transcript PCI in stable angina improves prognosis and is cost

Keynote Lecture
From RITA to SYNTAX
via COURAGE –
15 years on and what can we now tell
patients with multi-vessel disease about
their treatment options?
Patrick W. Serruys
Yoshinobu Onuma
Thorax Center, Erasmus MC, Rotterdam, the Netherlands
10:55-11:40, 28th January 2009
London Hilton Metropolitan Hotel
NO CONFLICT OF INTEREST
TO DECLARE
Déjà vu . . .
• CABRI Trial (Sir Magdi Yacoub) 1987, Antwerp
• ARTS Trial (Prof. F. Unger), 1996,
Rotterdam
• SYNTAX Trial (Prof. F. Mohr), 2004,
Frankfurt
Overview of the keynote lecture
• Meta-analysis of all the trials comparing PCI
and CABG (patient-level data)
• Meta-analysis of the trials comparing
multivessel stenting with BMS and CABG
(patient-level data)
• Critical appraisal of COURAGE
• Critical appraisal of FAME
• Personal view on lessons learned from the
Syntax
Overview of the keynote lecture
• Meta-analysis of all the trials comparing PCI
and CABG (patient-level data)
• Meta-analysis of the trials comparing
multivessel stenting with BMS and CABG
(patient-level data)
• Critical appraisal of COURAGE
• Critical appraisal of FAME
• Personal view on lessons learned from the
Syntax
•A MEDLINE search using the keywords “coronary stenting”, “coronary artery bypass
surgery”, and “multisystem/multivessel disease” was performed with the intention to select
and include all randomized clinical trials comparing PCI with stenting versus CABG in
patients with multivessel coronary artery disease. Finally, four trials were selected: the
ARTS-trail, the SoS-trial, the ERACI-2 trial and the MASS-2 trial.
•Principal investigators of each study group were contacted and individual patient data was
requested.
•The patient level based data was subsequently transferred to Dr. E. Boersma, Erasmus
University Medical Center, Rotterdam, NL and two of the authors (JD, PWS) analyzed and
interpreted the data.
Baseline and procedural characteristics and medications
Age (years)
Median
IQR
Range
Men
Diabetes mellitus
Hyperlipidemia
Hypertension
Family history of CAD
Current smoker
Previous MI
Peripheral vascular disease
Aspirin
Beta-blockers
Calcium channel blockers
Nitrates
Statins
Enrollment diagnosis*
Stable angina
Unstable Angina
Silent ischemia**
Ejection fraction
Median
IQR
Range
No. of segments with >50% stenosis
Median
IQR
Range
Complete revascularization
PCI with stenting
(1518 patients)
CABG
(1533 patients)
61.6
53.5 – 68.0
(30.2, 85.4)
76.5% (1162/1518)
18.1% (275/1518)
60.1% (910/1515)
50.5% (766/1518)
38.1% (498/1307)
28.3% (429/1516)
42.8% (650/1518)
7.0% (107/1518)
93.5% (1419/1518)
79.4% (1205/1518)
37.3% (566/1518)
68.1% (1033/1518)
40.9% (621/1517)
61.6
54.6 – 68.3
(31.9, 86.0)
77.1% (1182/1533)
17.5 (268/1533)
56.5% (866/1532)
51.7% (792/1533)
38.7% (514/1327)
26.5 (406/1533)
41.4% (635/1533)
8.2% (126/1533)
90.2% (1382/1533)
81.7% (1252/1533)
40.2% (617/1533)
69.7% (1068/1533)
39.5% (606/1533)
0.73
0.67
0.051
0.52
0.75
0.27
0.44
0.25
0.001
0.11
0.095
0.35
0.44
68.2% (1036/1518)
28.5% (432/1518)
3.5% (48/1358)
68.9% (1057/1533)
27.3 (418/1533)
2.6% (34/1330)
0.7
0.47
0.15
60
52 - 68
27, 92
60
51 - 67
26, 91
0.91
3
03-2
1, 9
62.0% (809/1304)
3
03-2
1, 8
89.4% (1180/1320)
0.92
P-value
0.37
<0.001
Event rates at 5 years
Total population (n=3051)
Kaplan Meier estimates
Hazard ratio
[95% CI]
Variables
PCI
(1518 pts)
CABGS
(1533 pts)
P-value
Death
8.50%
8.20%
0.95 [0.73 – 1.23]
0.69
Stroke
3.10%
3.60%
1.16 [0.73 – 1.83]
0.54
Myocardial infarction
7.30%
7.60%
0.91 [0.68 – 1.23]
0.54
Repeat revascularization
29.00%
7.90%
0.23 [0.18 – 0.29]
<0.001
Repeat PCI
21.50%
6.90%
0.29 [0.22 – 0.37]
<0.001
Repeat CABG
10.40%
1.50%
0.12 [0.07 – 0.21]
<0.001
Death, stroke or
myocardial infarction
16.70%
16.90%
1.04 [0.86 – 1.27]
0.69
Death, myocardial infarction
or repeat revascularization
37.10%
20.40%
0.50 [0.43 – 0.58]
<0.001
Death, stroke, myocardial
infarction or repeat
revascularization
39.20%
23.00%
0.53 [0.45 – 0.61]
<0.001
5y survival
100
CABG 91.8%
Overall survival (%)
90
PCI 91.5%
80
70
60
Logrank p-value 0.78
50
0
365
730
1095
1460
1825
Days
Days
Group
0
365
730
1095
1460
1825
PCI
1518
1472
1456
1440
1406
1347
CABG
1533
1479
1457
1439
1412
1349
Adjusted hazard ratio
and 95% CI for death
HR 0.95, 95% CI 0.63 - 1.43
ARTS
SoS
HR 0.56, 95% CI 0.33 – 0.95
MASS-II
HR 1.18, 95% CI 0.71 – 1.96
HR 1.69, 95% CI 0.91 – 3.16
ERACI-II
HR 0.97, 95% CI 0.76 – 1.24
All patients
0.1
Favors CABG
0.5 1.0
2.0
1
0
Favors PCI
•We found significant
heterogeneity in the treatment
effect for death at 5 years
between SoS and the other trials
(p=0.0074).
•In SoS, CABG was associated
with a 44% reduction in 5-year
mortality compared with PCI
with stenting (cumulative
survival: 95.5% versus 92.1%
respectively; HR 0.56 and 95%
CI 0.33 - 0.95), whereas no such
reduction was observed in the
remaining trials (91.2% versus
90.0% respectively; HR 1.15 and
95% CI 0.86 – 1.52).
•No heterogeneity was observed
between SoS and ARTS with
respect to the effects of CABG
versus PCI with stenting on 5year mortality (p=0.09).
5y Death/MI/Stroke
Survival free of death, stroke and myocardial
infarction (%)
100
90
PCI 83.3%
80
CABG 83.1%
70
60
Logrank p-value 0.64
50
0
365
730
1095
1460
1825
Days
Days
Group
0
365
730
1095
1460
1825
PCI
1518
1381
913
896
872
846
CABG
1533
1377
908
891
868
845
5y Revascularization
Survival free of repeat revascularizatoin (%)
100
CABG 92.1%
90
80
70
PCI 71.0%
60
Logrank p-value <0.0001
50
0
365
730
1095
1460
1825
Days
Days
Group
0
365
730
1095
1460
1825
PCI
1518
1204
772
740
707
665
CABG
1533
1428
927
911
882
855
5y MACCE
Survival free of death, stroke, myocardial infarction
and repeat revascularization (%)
100
90
CABG 77.0%
80
70
60
PCI 60.8%
Logrank p-value <0.0001
50
0
365
730
1095
1460
1825
Days
Days
Group
0
365
730
1095
1460
1825
PCI
1518
1153
729
691
657
616
CABG
1533
1332
867
846
812
785
Adjusted hazard ratio
and 95% CI for death, stroke or MI
HR 0.80, 95% CI 0.60 – 1.06
ARTS
HR 1.24, 95% CI 0.80 – 1.93
SoS
HR 1.08, 95% CI 0.72 – 1.61
MASS-II
ERACI-II
HR 1.74, 95% CI 1.07 – 2.83
All patients
HR 1.05, 95% CI 0.87 – 1.26
0.1
Favors CABG
0.5 1.0
2.0
1
0
Favors PCI
•No significant
heterogeneity for the
composite endpoint of
death, stroke and MI was
found for any of the clinical
and anatomical subgroup.
Adjusted hazard ratio and 95% CI
for all-cause death, stroke or MI
P for interaction
Age 62 years
Age >62 years
0.95
Men
Women
0.06
Hypertension
No hypertension
0.08
Hypercholesterolemia
No hypercholesterolemia
0.58
Diabetes
No diabetes
0.65
•In patients
withMIdiabetes, the cumulative incidence of mortality was 12.4%
0.84in
Previous
No previous
MI
the PCI group
as compared
to 7.9% in the CABG group (p=0.09).
LVEF 60
LVEF
cumulative>60incidence
0.54
•The
of death, stroke or MI in diabetics was similar following
PCI withTwo
stenting
and CABG (21.4% vs. 20.9% respectively, p=0.9).
0.84
vessel disease
Three vessel disease
•However,
the vascular
hazard
ratio for repeat revascularization in the diabetic subgroup
0.12
Peripheral
disease
No
peripheral
vascular
disease
was 0.18 (95% CI 0.11 – 0.29) due to a three-fold higher cumulative incidence of
repeat revascularization
in the PCI group (29.7% vs. 9.2%; p<0.001).
All patients
0.64
Favors PCI
0.1
Favors CABG
0.5
1.0
2.0
10
Overview of the keynote lecture
• Meta-analysis of all the trials comparing PCI
and CABG (patient-level data)
• Meta-analysis of the trials comparing
multivessel stenting with BMS and CABG
(patient-level data)
• Critical appraisal of COURAGE
• Critical appraisal of FAME
• Personal view on lessons learned from the
Syntax
In stable ischemic heart disease what
is the evidence that revascularization
reduces death or MI ?
PCI vs Conservative Therapy in
Nonacute CAD: a Meta-analysis
11 randomized trials (n=2950)
Risk Ratio: PCI compared to medical therapy
Mortality = 0.94 (0.72 to 1.24)
Cardiac death = 1.17 (0.88 to 1.57)
Myocardial Infarction = 1.28 (0.94 to 1.75)
Katritsis DG, Ioannidis JP Circ 2005, 111:2906-12
Angina/QOL at 1 Year: Med Rx vs. PCI
8 prior (major) randomized trials in
stable CAD
Trial
ACME
ACME 2
QOL
Angina
PCI better PCI better
«
PCI better
«
MASS
PCI better
ACIP
PCI better
RITA 2
AVERT
MASS II
TIME
ETT
«
PCI better
PCI better PCI better
PCI better PCI better
PCI better
PCI better PCI better
PCI better PCI better
PCI better
Refs in: Katritsis DG et al. Circulation 2005;111:2906-12.
Angina/QOL at 1 Year: Med Rx vs. PCI
9 prior (major) randomized trials in
stable CAD
Trial
ACME
ACME 2
QOL
Angina
PCI better PCI better
«
PCI better
«
MASS
PCI better
ACIP
PCI better
RITA 2
AVERT
MASS II
TIME
COURAGE
ETT
«
PCI better
PCI better PCI better
PCI better PCI better
PCI better
PCI better PCI better
PCI better PCI better
PCI better PCI better
PCI better
PCI better
Refs in: Katritsis DG et al. Circulation 2005;111:2906-12.
Why Should COURAGE not Change our Approach
to Patients with Stable Angina?
1.COURAGE confirms prior studies that
demonstrate that PCI is a superior
approach to relieve angina, reduce
medication requirements, and enhance
quality of life
2.No reasonable conclusions can be
drawn from COURAGE regarding
prevention of death/MI
Simulated Distribution of Anginal
Frequency in the COURAGE Trial
250
~42% of pts had absent or minimal
symptoms at baseline before Rx
Patients
200
Of symptomatic patients, the
median number of anginal episodes
per week was 3 [1, 6], with a mean
of 10
150
100
50
0
0
10
20
30
40
50
N episodes angina/week
Diamond, Kaul. JACC 2007
60
70
Simulated Distribution of Anginal
Frequency in the COURAGE Trial
250
~42% of pts had absent or minimal
symptoms at baseline before Rx
Patients
200
Of symptomatic patients, the
median number of anginal episodes
per week was 3 [1, 6], with a mean
of 6*
Who needed PCI within 1 year?
150
100
50
0
0
10
20
30
40
50
60
70
N episodes angina/week
* Recent correction by Courage investigators
Diamond, Kaul. JACC 2007
Simulated Distribution of Anginal
Frequency in the COURAGE Trial
250
~42% of pts had absent or minimal
symptoms at baseline before Rx
Patients
200
Of symptomatic patients, the
median number of anginal episodes
per week was 3 [1, 6], with a mean
of 6*
Who needed PCI within 1 year?
150
100
50
0
0
10
20
30
40
50
60
70
N episodes angina/week
* Recent correction by Courage investigators
Diamond, Kaul. JACC 2007
A North American Trial
19 US Non-VA Hospitals
387 pts (0.5 pts/mo/hosp)
(17% of total)
50 Hospitals
2,287 pts enrolled
15 VA Hospitals
between 6/99-1/04
968 pts (1.6 pts/mo/hosp)
(42% of total)
1 pt per hospital per
month
16 Canadian Hospitals
932 pts (1.5 pts/mo/hosp)
(41% of total)
Boden WE et al. NEJM 2007;356:1503-16
Does COURAGE Represent PCI
in the United States?
Canada
US VA
US non VA
962,732
(98.5%)
14,268
(1.5%)
Boden WE et al. NEJM 2007;356:1503-16
*US data of file, Boston Scientific
COURAGE :Subgroup Analyses
Death from any cause and nonfatal myocardial infarction
Baseline
Characteristics
Hazard Ratio (95% Cl)
Overall
1.05 (0.87–1.27)
Sex
Male
1.15 (0.93–1.42)
Female
0.65 (0.40–1.06)
Age
> 65
1.10 (0.83–1.46)
Health
Care
System
≤ 65
1.00 (0.77–1.32)
Race
White
(0.87–1.34)
Canadian 1.08 1.27
(0.90–1.78)
Not White
0.87 (0.54–1.42)
Health Care System
U.S. non-VA1.270.71
(0.80–1.38)
Canadian
(0.90–1.78)
U.S. Non-VA
0.71 (0.44–1.14)
U.S.
VA VA
1.061.06
(0.80–1.38)
U.S.
(0.80-1.38)
PCI Better
PCI
Medical
Therapy
0.19
0.19
0.19
0.18
0.18
0.26
0.24
0.16
0.22
0.16
0.19
0.17
0.18
0.14
0.15
0.17
0.21
0.14
0.19
0.15
0.22
0.22
0.25 0.50 1.00 1.50 1.75 2.00
0.24
0.21
0.22
0.22
Medical Therapy Better
Boden WE et al. NEJM 2007;356:1503-16
Death/MI (%) at 4.6 years
COURAGE Projections: 3-year death/MI
21% (OMT) vs. 16.4% (PCI + OMT) (22%↓)
30%
25%
OMT
PCI+OMT
20%
15%
P≈0.02
22% 22%
21%
17%
15%
14%
10%
5%
0%
27%↑

29%↓
Canada
US VA
US non-VA
Boden WE et al. NEJM 2007;356:1503-16
Nuclear Substudy
(n=314/2,287)
Hypothesis: Reduction in Ischemia will be greater for
patients randomized to PCI + OMT than for those
randomized to OMT
Serial Rest/Stress Myocardial Perfusion SPECT (MPS)
To compare patient management strategy for
ischemia reduction
Pre-Rx = Off Meds
Pre-Rx ischemia
PCI + OMT
(n=159)
OMT
(n=155)
Repeat MPS
at 6-18M
Repeat MPS
at 6-18M
Pre-Rx = On Meds
Shaw et al. J Nucl cardiol 2006; 13: 685-98
Myocardial Perfusion SPECT
Ischemia based on Total Perfusion Defect (TPD)
TPD: Quantitative Measure of defect extent & severity
% Ischemic Myocardium:
(Stress TPD-Rest TPD)
<5%:
Minimal “No Ischemia”
5.0-9.9%: Mild
≥10%:
Moderate-to-Severe
Significant Reduction
>5% Reduction in Ischemia
Shaw et al. Circulation 2008; 117: 1283-91
Slomka et al. J Nucl cardiol 2005; 12:66-77
Primary Endpoint: % of Patients with
Significant Ischemia Reduction
Ischemia Reduction ≥5%
(≥5% Myocardium, n=314)
50%
40%
33.3%
P = 0.004
30%
19.8%
20%
10%
0%
PCI+OMT
OMT
(n=159)
(n=155)
Shaw et al. Circulation 2008; 117: 1283-91
Rates of Death or MI by Residual
Ischemia on 6-18m MPS
Death or MI Rate (%)
P=0.02
P=0.023
40%
39.3%
P=0.063
30%
22.3%
20%
15.6%
10%
0%
0.0%
0%
1-4.9%
5-9.9%
=/> 10%
(n=23)
(n=141)
(n=88)
(n=62)
Shaw et al. Circulation 2008; 117: 1283-91
“A substudy of the COURAGE trial, which
showed that patients with the greatest relief of
ischemia had the lowest rates of death or
myocardial infarction, further supports the
concept that PCI should be guided by
physiological considerations and not solely by
anatomical ones.”
Fractional Flow Reserve versus Angiography for Guiding Percutaneous
Coronary Intervention, Tonino et al. NEJM Jan 15, 2009
Overview of the keynote lecture
• Meta-analysis of all the trials comparing
PCI and CABG (patient-level data)
• Meta-analysis of the trials comparing
multivessel stenting with BMS and CABG
(patient-level data)
• Critical appraisal of COURAGE
• Critical appraisal of FAME
• Personal view on lessons learned from
the Syntax
Conclusions
Routine measurement of FFR in patients with multivessel
coronary artery disease who are undergoing PCI with drugeluting stents significantly reduces the rate of the composite end
point of death, nonfatal myocardial infarction, and repeat
revascularization at 1 year.
Patient Characteristics
Characteristic
Indicated lesions per patient- no.
Angiography
Group
(N = 496)
2.7±0.9
Extent of occlusion — no. of lesions/total (%)
50–70% narrowing
40.7
71–90% narrowing
41.0
91–99% narrowing
15.3
Total occlusion
3.0
Patients with total occlusion- %
7.5
FFR Group
(N = 509)
2.8±1.0
P Value†
0.34
44.1
37.5
14.3
4.1
10.6
Quantitative coronary analysis
Extent of stenosis — %
Minimal luminal diameter — mm
Reference diameter — mm
Lesion length — mm
61.2±16.6
1.0±0.4
2.5±0.6
12.6±6.9
60.4±17.6
1.0±0.5
2.5±0.7
12.5±6.5
0.24
0.35
0.81
0.42
SYNTAX score
EQ-5D score
14.5±8.8
64.7±19.2
14.5±8.6
66.5±18.3
0.95
0.24
One-year Outcome
End Point
Events at 1 year — %
Composite of death, myocardial
infarction, and repeat vascularization
Death
Myocardial infarction
Repeat vascularization
Death or myocardial infarction
Total events — no.
Events per patient — no.
Functional status at 1 year
Patients without event and free from
angina— %
Patients free from angina — %
Antianginal medications
Score on EQ-5D visual-analogue scale
Relative Risk
Angiography
FFR
with FFR
Group
Group
P
guidance
(N = 496) (N = 509) Value† (95%CI)
18.3
13.2
0.02
3.0
1.8
0.19
8.7
5.7
0.07
9.5
6.5
0.08
11.1
7.3
0.04
113
76
0.23±0.53
0.15±0.41
0.02
67.6
73.0
0.07
77.9
81.3
0.2
1.23±0.74
73.7±16.0
1.20±0.76
74.5±15.7
0.48
0.65
0.72
(0.54–0.96)
0.58
(0.26–1.32)
0.66
(0.42–1.04)
0.68
(0.45–1.05)
0.66
(0.44–0.98)
98.2%
86.8%
97.0%
81.7%
RR = 0.72 [0.54-0.96], p=0.02
RR = 0.58 [0.26-1.32], p=0.19
94.3%
93.5%
91.3%
90.5%
RR = 0.66 [0.42-1.04], p=0.07
RR = 0.68 [0.45-1.05], p=0.08
Conclusions
• Routine measurement of FFR in patients
with multivessel coronary artery disease
who are undergoing PCI with drug-eluting
stents significantly reduces the rate of the
composite end point of death, nonfatal
myocardial infarction, and repeat
revascularization at 1 year.
Overview of the keynote lecture
• Meta-analysis of all the trials comparing
PCI and CABG (patient-level data)
• Meta-analysis of the trials comparing
multivessel stenting with BMS and CABG
(patient-level data)
• Critical appraisal of COURAGE
• Critical appraisal of FAME
• Personal view on lessons learned from
the Syntax
Past
Present
Background
At the time of the trial design (in 2003-2004), a
retrospective website survey of 104 medical
centers over a period of 3 months, showed that
12,072 patients (1/3 LM, 2/3 3VD) were
revascularized by surgery (2/3) or by PCI (1/3).
The SYNTAX randomized trial is an attempt to
provide an evidence-base to determine whether
this approach, which is already currently practiced,
is valid.
SYNTAX Primary Endpoint • Serruys
Kappetein et al, Eur J Cardiothorac Surg. 2006;29:486-491
TCT • 14 October 2008 • Slide 42
Background
In an attempt to answer this paradigm we asked
the following three questions:
How does modern CABG compare to PCI in highrisk patients eligible for both techniques?
Which patient group continues to be solely eligible
for CABG?
What characterizes complex patients not eligible
for CABG?
SYNTAX Primary Endpoint • Serruys
TCT • 14 October 2008 • Slide 43
Patient Profiling
Local Heart team (surgeon &
interventional cardiologist)
assessed each patient
in regards to:
Patient’s operative risk
(EuroSCORE & Parsonnet score)
Coronary lesion complexity
(newly developed SYNTAX
score)
Goal: SYNTAX score to provide
guidance on optimal
revascularization strategies for
patients with high-risk lesions
Sianos et al, EuroIntervention 2005;1:219-227
Valgimigli et al, Am J Cardiol 2007;99:1072-1081
Serruys et al, EuroIntervention 2007;3:450-459
SYNTAX Primary Endpoint • Serruys
Dominance
Number &
location of
lesions
Left Main
Calcification
SYNTAX
Thrombus
score
3 Vessel
Total
Occlusion
Bifurcation
Tortuosity
EuroInterv 2005;1:219-227
BARI classification of coronary segments
Leaman score, Circ 1981;63:285-299
Lesions classification ACC/AHA , Circ 2001;103:3019-3041
Bifurcation classification, CCI 2000;49:274-283
CTO classification, J Am Coll Cardiol 1997;30:649-656
TCT • 14 October 2008 • Slide 44
There is ‘3-vessel disease’ and ‘3-vessel
disease’
LCx 70-90%
Patient 1
Patient 2
LM 99%
LAD 99%
LAD 70-90%
LCx 100%
SYNTAX SCORE 21
SYNTAX SCORE 55
Patient 1
Patient 2
RCA2 70-90%
RCA3 70-90%
RCA 100%
SYNTAX Primary Endpoint • Serruys
TCT • 14 October 2008 • Slide 45
SYNTAX Score Distribution by Cohort
and Treatment Group
•CABG RCT
•PCI RCT
25
•% of Patients
Score
20
(23-32)
Score Tertile
Score Tertile
High Scores (33)
Low Scores (0-22)
15
10
5
0
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
•SYNTAX Score
SYNTAX Primary Endpoint • Serruys
TCT • 14 October 2008 • Slide 46
SYNTAX Score Distribution by Cohort
and Treatment Group
•CABG RCT
•PCI RCT
25
PCI Registry
•% of Patients
Score
20
(23-32)
Score Tertile
Score Tertile
High Scores (33)
Low Scores (0-22)
15
10
5
0
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
•SYNTAX Score
SYNTAX Primary Endpoint • Serruys
TCT • 14 October 2008 • Slide 48
SYNTAX Score Distribution by Cohort
and Treatment Group
•CABG RCT
•PCI RCT
•% of Patients
25
20
CABG Registry
PCI Registry
Score
(23-32)
Score Tertile
Score Tertile
High Scores (33)
Low Scores (0-22)
15
10
5
0
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
•SYNTAX Score
SYNTAX Primary Endpoint • Serruys
TCT • 14 October 2008 • Slide 49
SYNTAX Trial Design
62 EU Sites
+
23 US Sites
Pts with
de novo 3VD &
and/or
LM disease
Heart All
Team
(surgeon
interventionalist)
Total enrollment
N=3075
(n=4,337)
Amenable for both
Amenable for only one
treatment options
approach
Treatment preference treatment
(9.4%)
Stratification:
Stratification:
andor
Diabetes
ReferringLM
MD
pts. refused
LM and Diabetes
informed consent (7.0%)
Inclusion/exclusion (4.7%)
Randomized Arms
Registry Arms
Withdrew before consent Two
(4.3%)
n=1800
n= 1275
Other (1.8%)
Randomized Arms
Two Registry Arms
*
treatment
(1.2%)
n=1800Medical
TAXUS
PCI
CABG
CABG
n=897
3VD
66.3%
LM
33.7%
vs
vs
TAXUS
n=903
n=903
3VD
65.4%
CABG
2500
n=1077
n=1077
750 w/ f/u
71% enrolled (n=3,075)
5yr f/u no f/u
LM
34.6% 50 n=649 n=428
PCI
alln=198
captured w/
follow up
*
Taxus Express
Patient Characteristics
Notable Differences CABG RCT + Registry
CABG RCT
N=897
CABG Reg
N=644
65.0 ± 9.8
65.7 ± 9.4
78.9
80.7
29.1 ± 11.4
37.8 ± 13.3
Diabetes, %
28.5
29.7
Hypertension, %
77.0
73.5
Hyperlipidemia, %
77.2
76.4
Current smoker, %
22.0
21.9
Prior MI, %
33.8
33.5
Unstable angina, %
28.0
21.6
Add. EuroSCORE, mean±SD
3.8 ± 4.4
3.9 ± 2.7
Total Parsonnet score, mean±SD
8.4 ± 6.8
9.0 ± 7.1
Age, mean±SD (y)
Male, %
SYNTAX score, mean±SD
•*For descriptive purposes only; no statistical comparisons done
•Overall MACCE to 12 Months
CABG Registry
•Cumulative Event Rate (%)
•30
•20
•8.8%
•10
•0
•0
•Event Rate ± 1.5 SE
•6
•Months Since Allocation
•12
•Per-protocol population
Patient Characteristics
Notable Differences PCI RCT + Registry
TAXUS RCT
n=903
PCI Reg
n=192
65.2 ± 9.7
71.2 ± 10
76.4
70.3
28.4 ± 11.5
31.6 ± 12.3
Diabetes, %
28.2
35.4
Hyperlipidemia, %
78.7
67.5
Current smoker, %
18.5
11.2
Prior MI, %
31.9
40.4
Unstable angina, %
28.9
38.0
Add. EuroSCORE, mean±SD
3.8 ± 2.6
5.8 ± 3.1
Total Parsonnet score,
mean±SD
8.5 ± 7.0
14.4 ± 9.5
Age, mean±SD (y)
Male, %
SYNTAX score
•*For descriptive purposes only; no statistical comparisons done
•Overall MACCE to 12 Months
PCI Registry
•Cumulative Event Rate (%)
•30
•20.4%
•20
•10
•0
•0
•Event Rate ± 1.5 SE
•6
•Months Since Allocation
•12
•Per-protocol population
SYNTAX Trial Patient Distribution
CABG
registry
(N=1077) Enrolled
SYNTAX
trial patients
Randomized
(N=3075)
(N=1800)
PCI registry
(N=198)
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 55
Patient Characteristics (II)
Randomized Cohort
Patient-based
Total SYNTAX Score
Diffuse disease or small vessels, %
No. lesions, mean ± SD
CABG
N=897
TAXUS
N=903
P value
29.1 ± 11.4
28.4 ± 11.5
0.19
10.7
11.3
0.69
4.3 ± 1.8
0.44
4.4
± 1.8
3VD only, %
66.3
65.4
0.70
Left main, any, %
33.7
34.6
0.70
Left Main only
3.1
3.8
0.46
Left Main + 1 vessel
5.1
5.4
0.78
Left Main + 2 vessel
12.0
11.5
0.72
Left Main + 3 vessel
13.5
13.9
0.78
Total occlusion, %
22.2
24.2
0.33
Bifurcation, %
73.3
72.4
0.67
Trifurcation, %
10.6
10.7
0.92
SYNTAX Primary Endpoint • Serruys
TCT • 14 October 2008 • Slide 56
Procedural Characteristics
TAXUS Randomized Cohort
Patient-based
Staged procedure, %
TAXUS
N=903
14.1
Lesions treated/pt, mean ± SD
3.6 ± 1.6
No. stents implanted, mean ± SD
4.6  2.3
Total length implanted, mm ± SD
86.1  47.9
Range, mm
Long stenting (>100 mm), %
SYNTAX Primary Endpoint • Serruys
8 – 324
33.2
TCT • 14 October 2008 • Slide 57
Death/CVA/MI to 12 Months
CABG
Cumulative Event Rate (%)
20
(N=897)
TAXUS
(N=903)
P=0.98*
10
7.7%
7.6%
0
0
Event rate ± 1.5 SE. *Fisher exact test
SYNTAX Primary Endpoint • Serruys
6
Months Since Allocation
12
ITT population
TCT • 14 October 2008 • Slide 58
12 month MACCE, %
Combined Safety (Death/CVA/MI) to
12 months
P=0.99
CABG
TAXUS
P=0.39
P=0.29
P=0.96
15
10
7.7
7.6
6.6
8.0
10.3
9.2
10.1
7.0
5
0
n=897 n=903
n=549 n=546
n=348 n=357
Overall
3VD
LM
•SYNTAX Primary Endpoint • Serruys
n=221 n=231
Diabetes
Medically Treated Diabetes
•TCT • 14 October 2008 • Slide 59
SYNTAX Score Distribution by Cohort
and Treatment Group
•CABG RCT
•PCI RCT
25
•% of Patients
Score
20
(23-32)
Score Tertile
Score Tertile
High Scores (33)
Low Scores (0-22)
15
10
5
0
0
6
12
18
24
30
36
42
48
54
60
66
72
78
84
•SYNTAX Score
SYNTAX Primary Endpoint • Serruys
TCT • 14 October 2008 • Slide 60
MACCE to 12 Months by SYNTAX
Score Tertile
Low Scores (0-22)
CABG (N=274)
Cumulative Event Rate (%)
30
TAXUS (N=299)
P=0.71*
20
14.4%
13.5%
10
0
0
6
Months Since Allocation
Event Rate ±1.5 SE, *Fisher exact test; raw SYNTAX score for illustrative purposes only
PCI “Best Scenario” Interpretation • Serruys
12
RCT ITT pts; site-reported data
TCT • 14 October 2008 • Slide 61
MACCE to 12 Months by SYNTAX
Score Tertile Low Scores (0-22)
CABG (N=103)
TAXUS (N=118)
CABG (N=171)
TAXUS (N=181)
Mean baseline
SYNTAX Score
CABG
17.3 ± 3.7
TAXUS
17.3 ± 3.8
3VD
subset
P=0.66*
20
17.3%
15.2%
0
0
6
Months Since Allocation
Event rate ± 1.5 SE, *Fisher exact test
SYNTAX: Left Main Subset • Serruys
12 12
40
Cumulative Event Rate (%)
Cumulative Event Rate (%)
40
LM
subset
Mean baseline
SYNTAX Score
CABG 15.5 ± 4.3
TAXUS 15.7 ± 4.4
P=0.19*
20
13.0%
7.7%
0
0
6
Months Since Allocation
12
Calculated by core laboratory; ITT population
TCT • 14 October 2008 • Slide 62
What does this mean for clinicians?
Patients with low SYNTAX Scores have
comparable outcomes after
revascularization with PCI or CABG
These patients have less complex anatomy
Treatment will depend on individual patient
characteristics, patient preference and
physician choice
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 63
MACCE to 12 Months by SYNTAX
Score Tertile
Intermediate Scores (23-32)
CABG (N=300)
Cumulative Event Rate (%)
30
TAXUS (N=310)
P=0.10*
20
16.6%
11.7%
10
0
0
6
Months Since Allocation
Event Rate ±1.5 SE, *Fisher exact test; raw SYNTAX score for illustrative purposes only
PCI “Best Scenario” Interpretation • Serruys
12
RCT ITT pts; site-reported data
TCT • 14 October 2008 • Slide 64
MACCE to 12 Months by SYNTAX
Score Tertile
Intermediate Scores (23-32)
CABG (N=92)
TAXUS (N=195)
CABG (N=208)
TAXUS (N=207)
Mean baseline
SYNTAX Score
CABG
27.5 ± 2.7
TAXUS
27.4 ± 2.9
3VD
subset
P=0.02*
20
40
18.6%
10.0%
0
Cumulative Event Rate (%)
Cumulative Event Rate (%)
40
Mean baseline
SYNTAX Score
CABG
27.2 ± 3.0
TAXUS
27.0 ± 2.7
LM
subset
P=0.54*
20
15.5%
12.6%
0
0
6
12
Months Since Allocation
Event Rate ± 1.5 SE, *Fisher exact test
SYNTAX: 3VD • Mohr
0
6
12
Months Since Allocation
Calculated by core laboratory; ITT population
TCT • 14 October 2008 • Slide 65
What does this mean for clinicians?
MACCE is slightly, but not significantly,
increased in PCI patients with intermediate
SYNTAX Scores
This suggests that PCI is still a valid option
in patients with intermediate SYNTAX scores
Treatment will depend on the patients’
characteristics and comorbidity
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 66
MACCE to 12 Months by SYNTAX
Score Tertile
High Scores (33)
CABG (N=316)
Cumulative Event Rate (%)
30
TAXUS (N=290)
P<0.001*
23.3%
20
10.7%
10
0
0
6
Months Since Allocation
Event Rate ±1.5 SE, *Fisher exact test; raw SYNTAX score for illustrative purposes only
PCI “Best Scenario” Interpretation • Serruys
12
RCT ITT pts; site-reported data
TCT • 14 October 2008 • Slide 67
MACCE to 12 Months by SYNTAX
Score Tertile
High Scores (33)
CABG (N=166)
TAXUS (N=155)
CABG (N=150)
TAXUS (N=135)
Mean baseline
SYNTAX Score
CABG
41.0 ± 6.6
TAXUS
39.8 ± 6.0
40
3VD
subset
P=0.002*
21.5%
20
8.8%
0
Cumulative Event Rate (%)
Cumulative Event Rate (%)
40
Mean baseline
SYNTAX Score
CABG
42.1 ± 7.6
TAXUS
43.8 ± 9.1
LM
subset
P=0.008*
25.3%
20
12.9%
0
0
6
Months Since Allocation
Event Rate ± 1.5 SE, *Fisher exact test
SYNTAX: 3VD • Mohr
12
0
6
12
Months Since Allocation
Calculated by core laboratory; ITT population
TCT • 14 October 2008 • Slide 68
What does this mean for clinicians?
MACCE rates in PCI patients with high
SYNTAX Score were significantly higher than
in CABG patients
These patients have very complex anatomy
This suggests that PCI is most likely not a
viable option and these patients will remain
surgical candidates
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 69
SYNTAX Trial Patient Distribution
All Patients
CABG
registry
(N=1077)
-
SYNTAX
Scores
≥33
SYNTAX
Scores
23-32
PCI registry
(N=198)
All Patients
+/-
SYNTAX
Scores
0-22
All Patients
+
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 70
SYNTAX Trial Patient Distribution
Left main
CABG
registry
(N=1077)
-
SYNTAX
Scores
≥33
SYNTAX
Scores
23-32
PCI registry
(N=198)
Left main
+/-
SYNTAX
Scores
0-22
Left main
+
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 71
SYNTAX Trial Patient Distribution
3VD
CABG
registry
(N=1077)
-
SYNTAX
Scores
≥33
3VD
SYNTAX
Scores
23-32
PCI registry
(N=198)
SYNTAX
Scores
0-22
P=0.02
3VD
-
LM
3VD
+
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 72
SYNTAX Trial Design
62 EU Sites
+
23 US Sites
Heart
Team
(surgeon
& interventionalist)
All Pts
with
de novo
3VD and/or
Total enrollment
LM disease
(N=4,337)
N=3075
Amenable for both
Amenable for only one
treatment options
treatment approach
Treatment preference (9.4%)
Stratification:
Referring
MD or pts. refused
Stratification:
LM
Diabetes
informed
(7.0%)
LM and
andconsent
Diabetes
Inclusion/exclusion (4.7%)
Randomized Arms
Two
Registry Arms
Withdrew before consent
(4.3%)
N=1800
N=1275
Other (1.8%)
Randomized Arms
Two Registry Arms
*
Medical
treatment
(1.2%)
PCI
CABG
CABG n=1800 TAXUS
CABG
TAXUS
PCI
N=897
n=897
vs
N=903
n=903
2500
N=1077
n=1077
750 w/ f/u
71%
5yr f/u
LMDMvs 3VD
3VD
DM
Non
LM enrolled
DM
NonDM
n=649
(N=3,075)
66.3%
28.5% 33.7%
71.5%
34.6%
65.4% 71.8%
28.2%
73
no f/u
n=428
N=198
n=198
all captured w/
follow up
*
TAXUS Express
Combined Safety (Death/CVA/MI) to
12 months in Diabetic Patients
12 Mo Death/CVA/MI , %
CABG
P=0.11
8/60
•SYNTAX Primary Endpoint • Serruys
4/74
TAXUS
P=0.71
6/70
8/77
P=0.31
7/74
11/74
•TCT • 14 October 2008 • Slide 74
MACCE to 12 months
in Diabetic Patients
CABG
P=0.046
P=0.003
MACCE, %
P=0.78
TAXUS
11/60
•SYNTAX Primary Endpoint • Serruys
15/74
9/70
20/77
9/74
24/74
•TCT • 14 October 2008 • Slide 75
SYNTAX Trial Patient Distribution
CABG
registry
(N=1077)
SYNTAX
Scores
≥33
3VD +
LM with DM
SYNTAX
Scores
23-32
PCI registry
(N=198)
•SYNTAX Primary Endpoint • Serruys
SYNTAX
Scores
0-22
LM w/o
DM
•TCT • 14 October 2008 • Slide 76
Post SYNTAX
CABG
66%
PCI only
6%
CABG
+ 28%
PCI
Results of the SYNTAX trial suggest that 66 % of all
patients are still best treated with CABG, however,
for the remaining patients PCI is an excellent
alternative to surgery at least for one year
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 77
Conclusions
Using as criteria, a non-significant difference in
MACCE, we may state:
Results of the SYNTAX trial suggest that 66% of all
patients are still best treated with CABG, however,
for the remaining patients PCI (Syntax Score 0-22)
is an excellent alternative to surgery in multivessel
disease, in left main disease and in diabetic patients.
Left main disease, non-diabetic with score of 23-32
could also be treated by PCI.
PCI “Best Scenario” Interpretation • Serruys
TCT • 14 October 2008 • Slide 78