What’s inside the “FAME” ?

Chang-Wook Nam, MD, PhD

Keimyung University Dongsan medical center, Daegu, Korea

Fractional Flow Reserve

versus

Angiography for

Multivessel

Evaluation

Past of FAME

Current FAME

Future of FAME

Past of FAME

VS.Angiography FFR

Pijl NH, JACC 2007;49:2105

PCI of moderate coronary stenosis without

functional significance does not improve outcome

or anginal status and does not reduce the use of

anti-anginal medication.

The DEFER Study

Randomized

FFR-GuidedAngio-Guided

Composite of death,

MI and repeat revasc.

(MACE) at 1 year

Primary Endpoint

Cost-Effectiveness, MACE

and functional status at 2 years

Key Secondary Endpoints

Flow Chart

PCI performed on

indicated lesions

PCI performed on

indicated lesions

only if FFR ≤0.80

Patient with stenoses ≥ 50%

in at least 2 of the 3

major epicardial vessels

Angio-Guided

FFR-Guided

FFR 0.87

FFR 0.89

FFR 0.88

FFR 0.50

1 Year Event-Free Survival

FFR-guided

30 days

2.9% 90 days

3.8% 180 days

4.9% 360 days

5.1%

Angio-guided

Absolute Difference in MACE-Free Survival

Tonino PA, NEJM 2009;360:213-24.

Angio Better FFR Better

FFR

Less

Costly

Angio

Less

Costly

QALY

US

D

Bootstrap Simulation

1 Year Economic Evaluation

Fearon WF, Circ 2010;29.

Why FFR-guided PCI is better?

Large portion of intermediate lesions

Lesser intervention

Lesser adverse events

% Diameter Stenosis of

Indicated Lesions

PCI: 33.7 %

Defer: 66.3%

31.3%65.1%

1.2 %2.4%

Nam CW, JACC interv 2010;3:812-7

VS.Angiography FFR

FFR-Guided

Angio-Guidaed

730 days

4.5%

2 Year Event-Free Survival

Pijl NH, JACC 2010;56:177-84

2 Year Outcome of Deferred Lesions

94% (482)

513 Deferred Lesions in

509 FFR-Guided Patients

MI 6% (31)4.3% (22)

peri-procedural MI

1.6% (8) due to

new or stent

related lesionsOnly 1/513 or 0.2% of

deferred lesions

resulted in a late

myocardial infarction

Late MI 1.7% (9)

Pijl NH, JACC 2010;56:177-84

2 Year Outcome of Deferred Lesions

89.7% (460)

513 Deferred Lesions in

509 FFR-Guided Patients

TVR 10.3% (53)7.2% (37) in New lesion

or in Restenotic lesion

1.2% (6) w/o FFR or

despite FFR> 0.80

Only 1.9 % (10/513) of

deferred lesions clearly

progressed requiring

repeat revascularization

3.1% (16)

Pijl NH, JACC 2010;56:177-84

VS.CABG FFR-guided PCI

SYNTAX FAME

Cu

mu

lati

ve M

AC

E a

t 1

-year

(%)

PCI

CABGAngio-guided PCI

FFR-guided PCI

p = 0.002 p = 0.02

1 Year Outcomes of SYNTAX and FAME

SYNTAX FAME

Cu

mu

lati

ve M

AC

E a

t 2

-year

(%) PCI

CABGAngio-guided PCI

FFR-guided PCI

p < 0.001 p = 0.08

2 Year Outcomes of SYNTAX and FAME

PCICABG

Pati

en

ts, %

Pati

en

ts, %

Death/CVA/MI MACCERevasc

P=0.11 P<0.001 P<0.001

Death/MI MACERevasc

P=0.02 P=0.30 P=0.08

SYNTAX (n=1095) FAME (n=1005)

AngiographyFFR

TCT 2009

Why CABG is better in multi-vessel CAD?

Critical Area

before Red Zone

PCI betterPCI worse

Why CABG is better in multi-vessel CAD?

0 12 24

Months Since Allocation

Cu

mu

lati

ve E

ven

t R

ate

(%

)

20

40

0

0 12 24

Months Since Allocation

Cu

mu

lati

ve E

ven

t R

ate

(%

)

20

40

0

0 12 24

Months Since Allocation

Cu

mu

lati

ve E

ven

t R

ate

(%

)

20

40

P<0.001P=0.06P=0.63

MACCE to 2 Years by SYNTAX Score Tertile

TCT 2009

Low Scores

(0-22)

Intermediate Scores

(22-33)

High Scores

(33≤)

PCI (N=299)CABG (N=275)

The Selection of Patients with Multi-vessel CAD can Improve Outcomes

Wijns W, EHJ 2010;31:2501–2555.

Current Guidelines for MVD

But, can YOU

seriously believe

CORONARY

ANGIOGRAPHY ?

The Selection of Patients with Multi-vessel CAD can Improve Outcomes

“FFR-guided SYNTAX score (FSS)” would

predict 1-year clinical outcome better than the

“classic SYNTAX score (SS)” in patients with

multi-vessel coronary artery disease

undergoing percutaneous coronary intervention

Current FAME

FFR-Guided SYNTAX Score

for Risk Assessment

in Multi-vessel Coronary Artery Disease

FFR 0.86

FFR 0.86

FFR 0.90

FFR 0.90

FFR 0.92

Randomized

FFR-GuidedAngio-Guided

Composite of death,

MI and repeat revasc.

(MACE) at 1 year

Primary Endpoint

Cost-Effectiveness, MACE

and functional status at 2 years

Key Secondary Endpoints

Flow Chart

PCI performed on

indicated lesions

PCI performed on

indicated lesions

only if FFR ≤0.80

Patient with stenoses ≥ 50%

in at least 2 of the 3

major epicardial vessels

Classic SYNTAX score

Low SYNTAX score

Medium SYNTAX score

High SYNTAX score

37(23%)

25(15%)

101

(62%)

98

(59%)

69

(41%)

FFR-guided SYNTAX score

32%

Proportion of study population

167

(34%)

167

(34%)

163

(32%)

FFR-guided SYNTAX score

Low SYNTAX score

Medium SYNTAX score

High SYNTAX score

Classic SYNTAX score

Proportion of study population

167

(34%)

167

(34%)

163

(32%)

106

(21%)290

(59%)

101

(20%)

Cu

mu

lati

ve

Ra

te (

%)

P<0.001

P=0.001

Low risk

Medium risk

High risk

Cumulative MACE rate

Classic SYNTAX score FFR-guided SYNTAX score

P=0.005Low risk

Medium risk

High risk

Cu

mu

lati

ve

Ra

te (

%)

Classic SYNTAX score FFR-guided SYNTAX score

Cumulative Death or MI rate

Low risk

Medium risk

High risk

SYNTAX 1 Y FAME 1 Y

Cu

mu

lati

ve M

AC

E a

t 1-y

ea

r (%

)

PCI

CABGHigh FSS

Low-med FSS

p = 0.002

Outcomes of SYNTAX and FAME

p < 0.001

p < 0.001

SYNTAX 2 Y

FAME II

Future of FAME

VS.OMT FFR-guided PCI

COURAGE

Years

0 1 2 3 4 5 6

0.0

0.5

0.6

0.7

0.8

0.9

1.0

PCI + OMT

Optimal Medical Therapy (OMT)

Hazard ratio: 1.05

95% CI (0.87-1.27)

P = 0.62

7

Background

Boden WE, NEJM 2007;356:1503–1516.

Su

rviv

al

Fre

e o

f D

ea

th o

r M

I

BARI 2D PCI Stratum

Srinivas V et al ACC 2010

32.4%

p=0.001

16.2%

De

ath

or

MI

(%)

% Ischemia Reduction ≥5% Myocardium (n=105 Moderate-to-Severe Pre-Rx Ischemia)

COURAGE nuclear substudy

Shaw et al. Circ 2008;117:1283

FAME II Hypothesis

The overall hypothesis of the FAME II trial

is that FFR-guided PCI plus optimal

medical treatment is superior to optimal

medical treatment alone in patients with

stable coronary disease

Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years

Stable patients scheduled for one-,

two- or three vessel DES stenting

FFR in all indicated stenoses

There is at least one Stenosis

With FFR ≤ 0.80

1:1 Randomization

PCI+OMT OMT

Cohort A

There is no Stenosis

with an FFR ≤ 0.80

OMT

Cohort B

FAME III

Future of FAME

VS.CABG FFR-guided PCI

Fractional Flow Reserve

versus

Angiography for

Multivessel

Evaluation

Past of FAME: FAME original

Current FAME: FAME SYNTAX

Future of FAME: FAME II & III

If FFR is applicable in the patients with multi-

vessel CAD, the number of lower-risk patients

who usually are recommended PCI can be

dramatically increased.

CABG could be highly recommendable in the

high-risk patients with multi-vessel CAD classified

by FFR to hopefully improve outcomes.

Therefore, the selection of target vessels, the

method for revascularization, and the

determination of prognosis in patients with multi-

vessel CAD are improved by FFR-guided risk in

daily practice.

Take Home Messages