Optimal revascularization strategy in patients with three-vessel disease and/or left main disease The 2-year Outcomes of the SYNTAX Trial A. Pieter Kappetein,

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


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 ++


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


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


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



Core laboratory reported unless *Site-reported


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


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


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


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


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


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



20

40Before 1 year*

2.2% vs 0.6%P=0.003

After 1 year*

0.6% vs 0.7%P=0.82


Myocardial Infarction to 2 Years Myocardial Infarction to 2 Years

3.3%5.9%


Cu

mu

lati

ve E

ven

t R

ate

(%

)

ITT population

P=0.01



20

40Before 1 year*

3.3% vs 4.8%P=0.11

After 1 year*

0.1% vs 1.2%P=0.008


All-Cause Death/CVA/MI to 2 Years

P=0.44


Cu

mu

lati

ve E

ven

t R

ate

(%

)

ITT population

9.6%

10.8%



20

40Before 1 year*

7.7% vs 7.6%P=0.98

After 1 year*

2.2% vs 3.5%P=0.11


Repeat Revascularization to 2 YearsRepeat Revascularization to 2 Years

8.6%

17.4%


Cu

mu

lati

ve E

ven

t R

ate

(%

)

ITT population

P<0.001



20

40Before 1 year*

5.9% vs 13.5%P<0.001

After 1 year*

3.7% vs 5.6%P=0.06


MACCE to 2 Years

P<0.001


Cu

mu

lati

ve E

ven

t R

ate

(%

)

ITT population

16.3%

23.4%



20

40Before 1 year*

12.4% vs 17.8%P=0.002

After 1 year*

5.7% vs 8.3%P=0.03



Cu

mu

lati

ve E

ven

t R

ate

(%

)


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



Cu

mu

lati

ve E

ven

t R

ate

(%

)


MACCE to 2 Years by SYNTAX Score TercileIntermediate Scores (23-32)


P=0.06

22.8%

16.4%


CABG 27.4 ± 2.8

TAXUS 27.3 ± 2.8


20

40



Cu

mu

lati

ve E

ven

t R

ate

(%

)


MACCE to 2 Years by SYNTAX Score TercileHigh Scores (33)


P<0.001

28.2%

15.4%


CABG 41.5 ± 7.1

TAXUS 41.7 ± 7.8


20

40


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


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


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

Optimal revascularization strategy in patients with three-vessel disease and/or left main disease The 2-year Outcomes of the SYNTAX Trial A. Pieter Kappetein,

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