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Optimal revascularization strategy in Optimal revascularization strategy in patients with three-vessel disease patients with three-vessel disease
and/or left main diseaseand/or left main disease
The 2-year Outcomes of the SYNTAX The 2-year Outcomes of the SYNTAX TrialTrial
Optimal revascularization strategy in Optimal revascularization strategy in patients with three-vessel disease patients with three-vessel disease
and/or left main diseaseand/or left main disease
The 2-year Outcomes of the SYNTAX The 2-year Outcomes of the SYNTAX TrialTrial
A. Pieter Kappetein, MD PhDA. Pieter Kappetein, MD PhDErasmus MC, Rotterdam, NLErasmus MC, Rotterdam, NL
On behalf of the SYNTAX investigatorsOn behalf of the SYNTAX investigators
Clinical Trial Update IIIClinical Trial Update III2 September 2009, Room Barcelona Zone 22 September 2009, Room Barcelona Zone 2
9:24 AM to 9:37 AM 9:24 AM to 9:37 AM Conflicts of Interest: NoneConflicts of Interest: None
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 2
SYNTAX Study ObjectivesSYNTAX Study Objectives
With technological advances and changes in clinical practice, the respective values of coronary artery bypass surgery and percutaneous coronary intervention needed to be reassessed
The SYNTAX randomized trial is an attempt to provide an evidence base to determine the best treatment option for patients in a real-world population seen by the surgeon and the interventional cardiologist in their daily practice
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 3
SYNTAX Trial Design
De novo 3VD and/or LM (isolated, +1,2,3 VD)De novo 3VD and/or LM (isolated, +1,2,3 VD)
Limited Exclusion CriteriaLimited Exclusion Criteria Previous interventions , Acute MI with CPK>2x, Concomitant cardiac Previous interventions , Acute MI with CPK>2x, Concomitant cardiac surgerysurgery
Two Registry ArmsTwo Registry ArmsN=1275N=1275
Randomized ArmsRandomized ArmsN=1800N=1800
Heart Team (Surgeon & Interventional Heart Team (Surgeon & Interventional CardiologistCardiologist
Amenable for only one Amenable for only one treatment approachtreatment approach
Amenable for bothAmenable for bothtreatment optionstreatment options
Stratification: Stratification: LM and DiabetesLM and Diabetes
23 US Sites23 US Sites62 EU Sites62 EU Sites ++
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 4
Patient ProfilingPatient Profiling
Local Heart team (surgeon & interventional cardiologist) assessed each patient with 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;1:219-27Valgimigli et al, Am J Cardiol 2007;99:1072-81Serruys et al, EuroIntervention 2007;3:450-9
Coronary tree segments AHA classification and modified for the ARTS study, Circulation 1975; 51:5-40 & Semin Interv Cardiol 1999; 4:209-19
Modified Leaman score, Circ 1981;63:285-92Lesions classification ACC/AHA , Circ 2001;103:3019-
41Bifurcation classification, CCI 2000;49:274-83CTO classification, J Am Coll Cardiol 1997;30:649-56
www.syntaxscore.com
available now
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 5
Patients in SYNTAXPatients in SYNTAXRandomized Controlled Trial Intent-to-TreatRandomized Controlled Trial Intent-to-Treat
**TAXUS ExpressTAXUS Express
RCT: EnrolledN=1800
RCT: 1 Year Follow-upN=1740 (96.7%)
PCI*
n=903CABGn=897
PCI*
n=891CABGn=849
PCI*
n=885vsvs
vsvs
vsvs
RCT: 2 Year Follow-upN=1721 (95.6%)
CABGn=836
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 6
Patient CharacteristicsPatient CharacteristicsRandomized CohortRandomized Cohort
CABGN=897
TAXUSN=903 P value
Age*, mean ± SD (y) 65.0 ± 9.8 65.2 ± 9.7 0.55
Medically treated diabetes*, % 24.6 25.6 0.64
Additive euroSCORE*, mean ± SD 3.8 ± 2.7 3.8 ± 2.6 0.78
Total Parsonnet score*, mean ± SD 8.4 ± 6.8 8.5 ± 7.0 0.76
Total SYNTAX Score, mean ± SD 29.1 ±11.4 28.4 ±11.5 0.19
No. lesions, mean ± SD 4.4 ±1.8 4.3 ±1.8 0.44
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
Core laboratory reported unless *Site-reported
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 7
Death/CVA/MI rates were similar between CABG and PCIDeath/CVA/MI rates were similar between CABG and PCI Stroke was increased in CABG vs PCIStroke was increased in CABG vs PCI Repeat revascularization and MACCE were increased in PCI vs Repeat revascularization and MACCE were increased in PCI vs CABGCABG
Non-inferiority was not met for 12-month MACCE
Summary of 1-Year Results
P=0.98*
0 6 12
10
20
0
Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
7.6% 7.5%
KM Event Rate ± 1.5 SE. *Fisher’s Exact Test
Death/CVA/MI
0.6%2.2%
0 6 12
10
20
0
Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
P=0.003*
KM Event Rate ± 1.5 SE. *Fisher exact test
Stroke
P=0.002*
0 6 12
10
20
0
Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
12.1%
17.8%
KM Event Rate ± 1.5 SE. *Fisher exact test
MACCE
PCI (N=903)CABG (N=897)
Repeat Revasc.
5.9%
13.7%
0 6 12
10
20
0
Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
P<0.001*
KM Event Rate ± 1.5 SE. *Fisher’s Exact Test
Repeat
Revasc
CABG Group
PCI Group
PCI 4.8% 11.6%
CABG 1.3% 2.9%
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 8ITT population
P=0.24
6.2%4.9%
0 12 240
Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
TAXUS (N=903)CABG (N=897)
All-Cause Death to 2 YearsAll-Cause Death to 2 Years
20
40
0
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
Before 1 year*
3.5% vs 4.4%P=0.37
After 1 year*
1.5% vs 1.9%P=0.53
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 9
CVA to 2 Years CVA to 2 Years
1.4%2.8%
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
P=0.03
TAXUS (N=903)CABG (N=897)
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
20
40Before 1 year*
2.2% vs 0.6%P=0.003
After 1 year*
0.6% vs 0.7%P=0.82
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 10
Myocardial Infarction to 2 Years Myocardial Infarction to 2 Years
3.3%5.9%
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
P=0.01
TAXUS (N=903)CABG (N=897)
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
20
40Before 1 year*
3.3% vs 4.8%P=0.11
After 1 year*
0.1% vs 1.2%P=0.008
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 11
All-Cause Death/CVA/MI to 2 Years
P=0.44
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
9.6%
10.8%
TAXUS (N=903)CABG (N=897)
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
20
40Before 1 year*
7.7% vs 7.6%P=0.98
After 1 year*
2.2% vs 3.5%P=0.11
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 12
Repeat Revascularization to 2 YearsRepeat Revascularization to 2 Years
8.6%
17.4%
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
P<0.001
TAXUS (N=903)CABG (N=897)
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
20
40Before 1 year*
5.9% vs 13.5%P<0.001
After 1 year*
3.7% vs 5.6%P=0.06
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 13
MACCE to 2 Years
P<0.001
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
ITT population
16.3%
23.4%
TAXUS (N=903)CABG (N=897)
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
20
40Before 1 year*
12.4% vs 17.8%P=0.002
After 1 year*
5.7% vs 8.3%P=0.03
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 14
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
TAXUS (N=299)CABG (N=275)
P=0.63
19.4%17.4
%
Calculated by core laboratory; ITT population
MACCE to 2 Years by SYNTAX Score TercileLow Scores (0-22)
Mean baselineSYNTAX Score
CABG 16.6 ± 4.0
TAXUS 16.7 ± 4.1
Cumulative KM Event Rate ± 1.5 SE; log-rank P value
20
40
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 15
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
Calculated by core laboratory; ITT population
MACCE to 2 Years by SYNTAX Score TercileIntermediate Scores (23-32)
TAXUS (N=310)CABG (N=300)
P=0.06
22.8%
16.4%
Mean baselineSYNTAX Score
CABG 27.4 ± 2.8
TAXUS 27.3 ± 2.8
Cumulative KM Event Rate ± 1.5 SE; log-rank P value
20
40
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 16
0 12 24Months Since Allocation
Cu
mu
lati
ve E
ven
t R
ate
(%
)
Calculated by core laboratory; ITT population
MACCE to 2 Years by SYNTAX Score TercileHigh Scores (33)
TAXUS (N=290)CABG (N=315)
P<0.001
28.2%
15.4%
Mean baselineSYNTAX Score
CABG 41.5 ± 7.1
TAXUS 41.7 ± 7.8
Cumulative KM Event Rate ± 1.5 SE; log-rank P value
20
40
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 17
TAXUSCABG
Pati
en
ts,
%
Pati
en
ts,
%
ITT population
7.5
11.1
23.8
14.4
8.2
17.4
0
10
20
30
40
17.3
22.9
19.3
10.411.810.2
0
10
20
30
40
Death/CVA/MI MACCERevasc
Time-to Event; Log-rank P value
P=0.11 P<0.001 P<0.001
Death/CVA/MI MACCERevasc
P=0.48 P=0.01 P=0.27
2 Year Outcomes in 3VD and LM Subgroups
3 Vessel Diseasen=1095
Left Main Diseasen=705
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 18
Summary: I Summary: I
In the SYNTAX randomized patients, 2-year MACCE rates were significantly higher for PCI than CABG, mainly driven by higher repeat revascularization in the PCI arm.
Significant increase of MI compared to CABG at 2 years driven by higher PCI MI rate between years 1and 2Significantly higher CVA rate in CABG compared to PCI with the majority of CVAs occurring in the first year
Composite safety (death/CVA/MI) remains similar between arms at 2 years
MACCE rates at 2 years not significantly different for patients with a low (0-22) or intermediate (23-32) baseline SYNTAX Score; for patients with high SYNTAX Scores (≥33), MACCE continued to be increased at 2 years in patients treated with PCI
ESC 2009 • Two-year Outcomes of the SYNTAX Trial • Kappetein • Slide 19
In the predefined subgroups of patients with either 3VD or LM disease:
Safety outcomes (death/CVA/MI) in the 3VD group were similar for PCI and CABG, but the 2-year revascularization and MACCE rates favored CABG.
In the LM group, safety outcomes and MACCE rates were similar for PCI and CABG, but the 2-year revascularization rate was lower in the CABG group.
The 2-year SYNTAX results suggest that CABG remains the standard of care for patients with complex disease (high SYNTAX Scores); however, PCI may be an acceptable alternative revascularization method to CABG when treating patients with less complex (low or intermediate SYNTAX Score) disease.
SYNTAX patients will continue to be followed for 5 years.
Summary: II Summary: II