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