keynote lecture from rita to syntax via courage · overview of the keynote lecture •meta-analysis...

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

Keynote Lecture

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

•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.

PCI with stenting CABG

P-value (1518 patients) (1533 patients)

Age (years)

Median 61.6 61.6 0.37

IQR 53.5 – 68.0 54.6 – 68.3

Range (30.2, 85.4) (31.9, 86.0)

Men 76.5% (1162/1518) 77.1% (1182/1533) 0.73

Diabetes mellitus 18.1% (275/1518) 17.5 (268/1533) 0.67

Hyperlipidemia 60.1% (910/1515) 56.5% (866/1532) 0.051

Hypertension 50.5% (766/1518) 51.7% (792/1533) 0.52

Family history of CAD 38.1% (498/1307) 38.7% (514/1327) 0.75

Current smoker 28.3% (429/1516) 26.5 (406/1533) 0.27

Previous MI 42.8% (650/1518) 41.4% (635/1533) 0.44

Peripheral vascular disease 7.0% (107/1518) 8.2% (126/1533) 0.25

Aspirin 93.5% (1419/1518) 90.2% (1382/1533) 0.001

Beta-blockers 79.4% (1205/1518) 81.7% (1252/1533) 0.11

Calcium channel blockers 37.3% (566/1518) 40.2% (617/1533) 0.095

Nitrates 68.1% (1033/1518) 69.7% (1068/1533) 0.35

Statins 40.9% (621/1517) 39.5% (606/1533) 0.44

Enrollment diagnosis*

Stable angina 68.2% (1036/1518) 68.9% (1057/1533) 0.7

Unstable Angina 28.5% (432/1518) 27.3 (418/1533) 0.47

Silent ischemia** 3.5% (48/1358) 2.6% (34/1330) 0.15

Ejection fraction

Median 60 60 0.91

IQR 52 - 68 51 - 67

Range 27, 92 26, 91

No. of segments with >50% stenosis

Median 3 3 0.92

IQR 03-2 03-2

Range 1, 9 1, 8

Complete revascularization 62.0% (809/1304) 89.4% (1180/1320) <0.001

Baseline and procedural characteristics and medications

Event rates at 5 years

Total population (n=3051) Kaplan Meier estimates Hazard ratio [95% CI]

Variables PCI CABGS P-value

(1518 pts) (1533 pts)

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

Days

Logrank p-value 0.78

0 365 730 1095 1460 1825

50

60

70

80

90

100

Ov

era

ll s

urv

ival (%

) PCI 91.5%

CABG 91.8%

Group 0 365 730 1095 1460 1825

PCI 1518 1472 1456 1440 1406 1347

CABG 1533 1479 1457 1439 1412 1349

Days

0.1 1.0 1

0

0.5 2.0

Favors PCI Favors CABG

HR 0.56, 95% CI 0.33 – 0.95

HR 0.95, 95% CI 0.63 - 1.43

HR 1.18, 95% CI 0.71 – 1.96

HR 1.69, 95% CI 0.91 – 3.16

HR 0.97, 95% CI 0.76 – 1.24

SoS

ARTS

MASS-II

ERACI-II

All patients

Adjusted hazard ratio and 95% CI for death

•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 5-year mortality (p=0.09).

Group 0 365 730 1095 1460 1825

PCI 1518 1381 913 896 872 846

CABG 1533 1377 908 891 868 845

5y Death/MI/Stroke

PCI 83.3%

CABG 83.1%

Logrank p-value 0.64

50

60

70

80

90

100

Su

rviv

al fr

ee o

f d

eath

, str

oke a

nd

myo

card

ial

infa

rcti

on

(%

)

Days

0 365 730 1095 1460 1825

Days

Group 0 365 730 1095 1460 1825

PCI 1518 1204 772 740 707 665

CABG 1533 1428 927 911 882 855

5y Revascularization

PCI 71.0%

CABG 92.1%

Logrank p-value <0.0001

50

60

70

80

90

100

Su

rviv

al fr

ee o

f re

peat

rev

ascu

lari

zato

in (

%)

Days

0 365 730 1095 1460 1825

Days

Group 0 365 730 1095 1460 1825

PCI 1518 1153 729 691 657 616

CABG 1533 1332 867 846 812 785

5y MACCE

PCI 60.8%

CABG 77.0%

Logrank p-value <0.0001

50

60

70

80

90

100

Su

rviv

al fr

ee o

f d

eath

, str

oke, m

yo

card

ial

infa

rcti

on

an

d r

ep

eat

rev

ascu

lari

zati

on

(%

)

Days

0 365 730 1095 1460 1825

Days

SoS

ARTS

MASS-II

ERACI-II

All patients

0.1 1.0 1

0

0.5 2.0


HR 1.24, 95% CI 0.80 – 1.93

HR 0.80, 95% CI 0.60 – 1.06

HR 1.08, 95% CI 0.72 – 1.61

HR 1.74, 95% CI 1.07 – 2.83

HR 1.05, 95% CI 0.87 – 1.26

Adjusted hazard ratio and 95% CI for death, stroke or MI

•No significant heterogeneity for the composite endpoint of death, stroke and MI was found for any of the clinical and anatomical subgroup.

Hypercholesterolemia No hypercholesterolemia

Diabetes No diabetes

Previous MI No previous MI

LVEF 60 LVEF >60

Two vessel disease Three vessel disease

Peripheral vascular disease No peripheral vascular disease

All patients

0.95

0.06

0.58

0.65

0.84

0.54

0.84

0.12

P for interaction

0.1 1.0 10 0.5 2.0


Age 62 years Age >62 years

Men Women

Hypertension No hypertension

0.08

0.64

Adjusted hazard ratio and 95% CI for all-cause death, stroke or MI

•In patients with diabetes, the cumulative incidence of mortality was 12.4% in the PCI group as compared to 7.9% in the CABG group (p=0.09). •The cumulative incidence of death, stroke or MI in diabetics was similar following PCI with stenting and CABG (21.4% vs. 20.9% respectively, p=0.9). •However, the hazard ratio for repeat revascularization in the diabetic subgroup 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).

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

In stable ischemic heart disease what is the evidence that revascularization

reduces death or MI ?

Angina/QOL at 1 Year: Med Rx vs. PCI

Trial QOL Angina ETT

ACME PCI better PCI better PCI better

ACME 2 « « « MASS PCI better

ACIP PCI better PCI better

RITA 2 PCI better PCI better

AVERT PCI better PCI better PCI better

MASS II PCI better PCI better

TIME PCI better PCI better PCI better

8 prior (major) randomized trials in stable CAD

Refs in: Katritsis DG et al. Circulation 2005;111:2906-12.

Angina/QOL at 1 Year: Med Rx vs. PCI

Trial QOL Angina ETT

ACME PCI better PCI better PCI better

ACME 2 « « « MASS PCI better

ACIP PCI better PCI better

RITA 2 PCI better PCI better

AVERT PCI better PCI better PCI better

MASS II PCI better PCI better

TIME PCI better PCI better PCI better

COURAGE PCI better PCI better PCI better

Refs in: Katritsis DG et al. Circulation 2005;111:2906-12.

9 prior (major) randomized trials in stable CAD

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

Why Should COURAGE not Change our Approach to Patients with Stable Angina?

Pa

tie

nts

0

50

100

150

200

250

0 10 20 30 60 70 40 50

N episodes angina/week

Simulated Distribution of Anginal Frequency in the COURAGE Trial

Diamond, Kaul. JACC 2007

~42% of pts had absent or minimal symptoms at baseline before Rx

Of symptomatic patients, the median number of anginal episodes per week was 3 [1, 6], with a mean of 10

Pa

tie

nts

0

50

100

150

200

250

0 10 20 30 60 70 40 50

N episodes angina/week

Simulated Distribution of Anginal Frequency in the COURAGE Trial

Diamond, Kaul. JACC 2007

Who needed PCI within 1 year?

~42% of pts had absent or minimal symptoms at baseline before Rx

Of symptomatic patients, the median number of anginal episodes per week was 3 [1, 6], with a mean of 6*

* Recent correction by Courage investigators

A North American Trial

50 Hospitals

2,287 pts enrolled between 6/99-1/04

1 pt per hospital per month

19 US Non-VA Hospitals 387 pts (0.5 pts/mo/hosp)

(17% of total)

15 VA Hospitals 968 pts (1.6 pts/mo/hosp)

(42% of total)

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?

962,732 (98.5%)

14,268 (1.5%)

Canada US VA US non VA


*US data of file, Boston Scientific

COURAGE :Subgroup Analyses Death from any cause and nonfatal myocardial infarction

PCI Better Medical Therapy Better

Baseline Characteristics Hazard Ratio (95% Cl) PCI

Medical Therapy

0.25

Overall 1.05 (0.87–1.27) 0.19 0.19 Sex Male 1.15 (0.93–1.42) 0.19 0.18 Female 0.65 (0.40–1.06) 0.18 0.26 Age > 65 1.10 (0.83–1.46) 0.24 0.22 ≤ 65 1.00 (0.77–1.32) 0.16 0.16 Race White 1.08 (0.87–1.34) 0.19 0.18 Not White 0.87 (0.54–1.42) 0.19 0.24 Health Care System Canadian 1.27 (0.90–1.78) 0.17 0.14 U.S. Non-VA 0.71 (0.44–1.14) 0.15 0.21 U.S. VA 1.06 (0.80–1.38) 0.22 0.22

1.75 2.00 1.00 0.50 1.50


Health Care System

Canadian 1.27 (0.90–1.78) 0.17 0.14

U.S. non-VA 0.71 (0.80–1.38) 0.15 0.21

U.S. VA 1.06 (0.80-1.38) 0.22 0.22

COURAGE Projections: 3-year death/MI

21% (OMT) vs. 16.4% (PCI + OMT) (22%↓)

14%

22% 21%

17%

22%

15%

0%

5%

10%

15%

20%

25%

30%

Canada US VA US non-VA

OMT

PCI+OMT

De

ath

/M

I (%

) a

t 4

.6 y

ea

rs

29%↓ 27%↑

P≈0.02


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)

Repeat MPS at 6-18M

Repeat MPS at 6-18M

Shaw et al. J Nucl cardiol 2006; 13: 685-98

Pre-Rx ischemia Pre-Rx = Off Meds

Pre-Rx = On Meds

PCI + OMT (n=159)

OMT (n=155)

To compare patient management strategy for ischemia reduction

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

33.3%

19.8%

0%

10%

20%

30%

40%

50%

PCI+OMT OMT

P = 0.004

Isch

em

ia R

ed

ucti

on

≥5

%

(n=159) (n=155)

Primary Endpoint: % of Patients with Significant Ischemia Reduction

(≥5% Myocardium, n=314)


22.3%

39.3%

0.0%

15.6%

0%

10%

20%

30%

40%

0% 1-4.9% 5-9.9%

Rates of Death or MI by Residual Ischemia on 6-18m MPS

De

ath

or

MI

Ra

te (

%)

(n=23) (n=141) (n=88) (n=62)

=/> 10%

P=0.063

P=0.023

P=0.02


“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

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.

Characteristic

Angiography Group

(N = 496) FFR Group (N = 509) P Value†

Indicated lesions per patient- no. 2.7±0.9 2.8±1.0 0.34

Extent of occlusion — no. of lesions/total (%)

50–70% narrowing 40.7 44.1

71–90% narrowing 41.0 37.5

91–99% narrowing 15.3 14.3

Total occlusion 3.0 4.1

Patients with total occlusion- % 7.5 10.6

Quantitative coronary analysis

Extent of stenosis — % 61.2±16.6 60.4±17.6 0.24

Minimal luminal diameter — mm 1.0±0.4 1.0±0.5 0.35

Reference diameter — mm 2.5±0.6 2.5±0.7 0.81

Lesion length — mm 12.6±6.9 12.5±6.5 0.42

SYNTAX score 14.5±8.8 14.5±8.6 0.95

EQ-5D score 64.7±19.2 66.5±18.3 0.24

Patient Characteristics

End Point

Angiography Group

(N = 496)

FFR Group

(N = 509) P

Value†

Relative Risk with FFR guidance (95%CI)

Events at 1 year — %

Composite of death, myocardial infarction, and repeat vascularization

18.3 13.2 0.02 0.72

(0.54–0.96)

Death 3.0 1.8 0.19

0.58 (0.26–1.32)

Myocardial infarction 8.7 5.7 0.07

0.66 (0.42–1.04)

Repeat vascularization 9.5 6.5 0.08

0.68 (0.45–1.05)

Death or myocardial infarction 11.1 7.3 0.04

0.66 (0.44–0.98)

Total events — no. 113 76

Events per patient — no. 0.23±0.53 0.15±0.41 0.02

Functional status at 1 year

Patients without event and free from angina— %

67.6 73.0 0.07

Patients free from angina — % 77.9 81.3 0.2

Antianginal medications 1.23±0.74 1.20±0.76 0.48

Score on EQ-5D visual-analogue scale 73.7±16.0 74.5±15.7 0.65

One-year Outcome

81.7%

86.8%

91.3%

94.3%

97.0%

98.2%

90.5%

93.5%

RR = 0.72 [0.54-0.96], p=0.02 RR = 0.58 [0.26-1.32], p=0.19

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.

Past

Present

SYNTAX Primary Endpoint • Serruys TCT • 14 October 2008 • Slide 42

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.

Background

Kappetein et al, Eur J Cardiothorac Surg. 2006;29:486-491


How does modern CABG compare to PCI in high-risk patients eligible for both techniques?

Which patient group continues to be solely eligible for CABG?

What characterizes complex patients not eligible for CABG?

Background

In an attempt to answer this paradigm we asked the following three questions:


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

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

Tortuosity

Thrombus

Bifurcation

Total Occlusion

3 Vessel

Left Main

EuroInterv 2005;1:219-227

Dominance

Calcification

Number & location of

lesions

SYNTAX score


Patient 1

Patient 1 Patient 2

Patient 2

SYNTAX SCORE 21 SYNTAX SCORE 55

LCx 70-90%

LAD 70-90%

RCA2 70-90%

RCA3 70-90%

LM 99%

LCx 100%

LAD 99%

RCA 100%

There is ‘3-vessel disease’ and ‘3-vessel disease’


SYNTAX Score Distribution by Cohort and Treatment Group

•SYNTAX Score

•%

of

Pati

ents

•CABG RCT •PCI RCT

0

5

10

15

20

25

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

Score Tertile Low Scores (0-22)

Score (23-32) Score Tertile

High Scores (33)



•SYNTAX Score

•%

of

Pati

ents

•CABG RCT •PCI RCT PCI Registry



High Scores (33)

0

5

10

15

20

25

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84



•SYNTAX Score

•%

of

Pati

ents

•CABG RCT CABG Registry •PCI RCT PCI Registry

0

5

10

15

20

25

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84



High Scores (33)

50

71% enrolled (n=3,075)

All Pts with de novo 3VD and/or LM disease (n=4,337)

Treatment preference (9.4%)

Referring MD or pts. refused informed consent (7.0%)

Inclusion/exclusion (4.7%)

Withdrew before consent (4.3%)

Other (1.8%)

Medical treatment (1.2%) TAXUS n=903

PCI n=198

CABG n=1077

CABG n=897

no f/u n=428

5yr f/u n=649

PCI all captured w/

follow up

CABG 2500

750 w/ f/u vs

Total enrollment N=3075

Stratification: LM and Diabetes

Two Registry Arms

Randomized Arms

n=1800

Two Registry Arms

n= 1275 Randomized Arms

n=1800

Heart Team (surgeon & interventionalist)

PCI n=198

CABG n=1077

Amenable for only one treatment approach

TAXUS*

n=903 CABG n=897

vs

Amenable for both treatment options

Stratification: LM and Diabetes

LM 33.7%

3VD 66.3%

LM 34.6%

3VD 65.4%

23 US Sites 62 EU Sites +

SYNTAX Trial Design

*Taxus Express

CABG RCT N=897

CABG Reg N=644

Age, mean±SD (y) 65.0 ± 9.8 65.7 ± 9.4

Male, % 78.9 80.7

SYNTAX score, mean±SD 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

Patient Characteristics Notable Differences CABG RCT + Registry

•*For descriptive purposes only; no statistical comparisons done

•0 •12

•C

um

ula

tive E

vent

Rate

(%

)

•Event Rate ± 1.5 SE

•10

•20

•30

•0

•Months Since Allocation •6

•Per-protocol population

•Overall MACCE to 12 Months CABG Registry

•8.8%

Patient Characteristics Notable Differences PCI RCT + Registry

TAXUS RCT n=903

PCI Reg n=192

Age, mean±SD (y) 65.2 ± 9.7 71.2 ± 10

Male, % 76.4 70.3

SYNTAX score 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

•*For descriptive purposes only; no statistical comparisons done

•0 •12

•C

um

ula

tive E

vent

Rate

(%

)

•Event Rate ± 1.5 SE

•10

•20

•30

•0

•Months Since Allocation •6

•Per-protocol population

•Overall MACCE to 12 Months PCI Registry

•20.4%

PCI “Best Scenario” Interpretation • Serruys TCT • 14 October 2008 • Slide 55

Enrolled SYNTAX

trial patients

(N=3075)

SYNTAX Trial Patient Distribution

CABG registry (N=1077)

Randomized

(N=1800)

PCI registry (N=198)


Patient Characteristics (II) Randomized Cohort

Patient-based

CABG N=897

TAXUS N=903 P value

Total SYNTAX Score 29.1 ± 11.4 28.4 ± 11.5 0.19

Diffuse disease or small vessels, % 10.7 11.3 0.69

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



Total occlusion, % 22.2 24.2 0.33

Bifurcation, % 73.3 72.4 0.67

Trifurcation, % 10.6 10.7 0.92


Staged procedure, % 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 8 – 324

Long stenting (>100 mm), % 33.2

Procedural Characteristics TAXUS Randomized Cohort

TAXUS

N=903 Patient-based


Death/CVA/MI to 12 Months

P=0.98*

0 6 12

10

20

0

Months Since Allocation

Cum

ula

tive E

vent

Rate

(%

)

ITT population

7.7% 7.6%

TAXUS (N=903) CABG (N=897)

Event rate ± 1.5 SE. *Fisher exact test

•SYNTAX Primary Endpoint • Serruys •TCT • 14 October 2008 • Slide 59

7.76.6

9.210.3

7.6 8.07.0

10.1

0

5

10

15

Overall 3VD LM Diabetes

Combined Safety (Death/CVA/MI) to 12 months

TAXUS CABG

P=0.99

12

month

MA

CC

E, %

P=0.39 P=0.96 P=0.29

n=897 n=903 n=221 n=231 n=348 n=357 n=549 n=546

Medically Treated Diabetes



•SYNTAX Score

•%

of

Pati

ents

•CABG RCT •PCI RCT

0

5

10

15

20

25

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84



High Scores (33)



13.5%

14.4%

P=0.71*

0 6 12

20

30

0


Cum

ula

tive E

vent

Rate

(%

)

10

RCT ITT pts; site-reported data

MACCE to 12 Months by SYNTAX Score Tertile Low Scores (0-22)

Event Rate ±1.5 SE, *Fisher exact test; raw SYNTAX score for illustrative purposes only

SYNTAX: Left Main Subset • Serruys TCT • 14 October 2008 • Slide 62

7.7%

13.0%

Mean baseline

SYNTAX Score

CABG 15.5 ± 4.3

TAXUS 15.7 ± 4.4

0 6 12

20

40

0


Cum

ula

tive E

vent

Rate

(%

)

TAXUS (N=118)

CABG (N=103)

P=0.19*

Event rate ± 1.5 SE, *Fisher exact test Calculated by core laboratory; ITT population

MACCE to 12 Months by SYNTAX Score Tertile Low Scores (0-22)

12

17.3%

15.2%

Mean baseline

SYNTAX Score

CABG 17.3 ± 3.7

TAXUS 17.3 ± 3.8

P=0.66*

0 6

20

40

0


Cum

ula

tive E

vent

Rate

(%

)

12

LM subset

3VD subset

TAXUS (N=181)

CABG (N=171)


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



16.6%

11.7%

P=0.10*

0 6 12

20

30

0


Cum

ula

tive E

vent

Rate

(%

)

10

MACCE to 12 Months by SYNTAX Score Tertile Intermediate Scores (23-32)

RCT ITT pts; site-reported data Event Rate ±1.5 SE, *Fisher exact test; raw SYNTAX score for illustrative purposes only

SYNTAX: 3VD • Mohr TCT • 14 October 2008 • Slide 65

P=0.02*

Calculated by core laboratory; ITT population Event Rate ± 1.5 SE, *Fisher exact test

Mean baseline

SYNTAX Score

CABG 27.5 ± 2.7

TAXUS 27.4 ± 2.9

0 6 12

20

40

0


Cum

ula

tive E

vent

Rate

(%

)

18.6%

10.0%

15.5%

12.6%

Mean baseline

SYNTAX Score

CABG 27.2 ± 3.0

TAXUS 27.0 ± 2.7

0 6 12

20

40

0


Cum

ula

tive E

vent

Rate

(%

)

LM subset

3VD subset

TAXUS (N=195)

CABG (N=92)

TAXUS (N=207)

CABG (N=208)

MACCE to 12 Months by SYNTAX Score Tertile Intermediate Scores (23-32)

P=0.54*


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




23.3%

10.7%

P<0.001*

0 6 12

20

30

0


Cum

ula

tive E

vent

Rate

(%

)

10

MACCE to 12 Months by SYNTAX Score Tertile High Scores (33)

RCT ITT pts; site-reported data Event Rate ±1.5 SE, *Fisher exact test; raw SYNTAX score for illustrative purposes only

SYNTAX: 3VD • Mohr TCT • 14 October 2008 • Slide 68

21.5%

8.8%

Mean baseline

SYNTAX Score

CABG 41.0 ± 6.6

TAXUS 39.8 ± 6.0

0 6 12

20

40

0


Cum

ula

tive E

vent

Rate

(%

)

P=0.002*

Calculated by core laboratory; ITT population Event Rate ± 1.5 SE, *Fisher exact test

P=0.008*

25.3%

12.9%

Mean baseline

SYNTAX Score

CABG 42.1 ± 7.6

TAXUS 43.8 ± 9.1

0 6 12

20

40

0


Cum

ula

tive E

vent

Rate

(%

)

LM subset

3VD subset

TAXUS (N=155)

CABG (N=166)

TAXUS (N=135)

CABG (N=150)

MACCE to 12 Months by SYNTAX Score Tertile High Scores (33)


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






SYNTAX Scores ≥33

SYNTAX Scores 23-32

SYNTAX Scores 0-22

+

-

+/-

All Patients

All Patients

All Patients





SYNTAX Scores ≥33

SYNTAX Scores 23-32

SYNTAX Scores 0-22

+

-

+/-

Left main

Left main

Left main





SYNTAX Scores ≥33

SYNTAX Scores 0-22

+

-

-

3VD

3VD

3VD

3VD

LM

SYNTAX Scores 23-32

P=0.02

73

71% enrolled

(N=3,075)

All Pts with de novo 3VD and/or

LM disease (N=4,337)

Treatment preference (9.4%)

Referring MD or pts. refused

informed consent (7.0%)

Inclusion/exclusion (4.7%)

Withdrew before consent (4.3%)

Other (1.8%)

Medical treatment (1.2%) TAXUS

n=903

PCI

n=198

CABG

n=1077 CABG

n=897

no f/u

n=428 5yr f/u

n=649

PCI all captured w/

follow up

CABG 2500

750 w/ f/u

vs

Total enrollment N=3075

Stratification:

LM and Diabetes

Two Registry Arms

Randomized Arms n=1800

Two Registry Arms N=1275

Randomized Arms N=1800

Heart Team (surgeon & interventionalist)

PCI

N=198 CABG

N=1077

Amenable for only one

treatment approach

TAXUS*

N=903 CABG

N=897 vs

Amenable for both

treatment options

Stratification:

LM and Diabetes

LM

33.7% 3VD

66.3% LM

34.6% 3VD

65.4% DM

28.5%

Non DM

71.5% NonDM

71.8%

DM

28.2%

23 US Sites 62 EU Sites +

SYNTAX Trial Design

*TAXUS Express


Combined Safety (Death/CVA/MI) to 12 months in Diabetic Patients

TAXUS CABG

P=0.11

12

Mo D

eath

/C

VA

/M

I ,

%

8/60 4/74 6/70 8/77 7/74 11/74

P=0.71 P=0.31


MACCE to 12 months in Diabetic Patients

TAXUS CABG

P=0.78

MA

CC

E, %

11/60 15/74 9/70 20/77 9/74 24/74

P=0.046 P=0.003





SYNTAX Scores ≥33

SYNTAX Scores 23-32

SYNTAX Scores 0-22

3VD +

LM with DM

LM w/o

DM


Post SYNTAX

CABG 66%

PCI only

CABG +

PCI 28%

6%

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


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.

keynote lecture from rita to syntax via courage · overview of the keynote lecture •meta-analysis...

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