1. FAME 2 Report of the Primary Endpoint
Fractional Flow Reserve–Guided PCI
for Stable Coronary Disease
FAME 2
Report of the Primary Endpoint
Clinicaltrials.gov NCT
Bernard De Bruyne, William F Fearon, Nico HJ Pijls,
Emanuele Barbato, Pim AL Tonino, Peter Juni
for the FFR vs Angiography for Multivessel Evaluation 2
(FAME 2) study group

2. Study Supported by St. Jude Medical
Potential conflicts of interest
Speaker’s name: Bernard De Bruyne
 I have the following potential conflicts of interest to report:
 Research contracts  Consulting
 Employment in industry
 Stockholder of a healthcare company
 Owner of a healthcare company
 Other(s)
 I do not have any potential conflict of interest
Study Supported by St. Jude Medical

3. FAME 2 Background FAME 2 Objective
In patients with stable coronary artery disease (CAD),
PCI has not been shown to improve ‘hard endpoints’.
In previous trials comparing PCI and Medical Therapy
(MT), neither FFR-guidance nor DES were used.
(‘contemporary PCI’).
FAME 2 Objective
To compare the rate of death, myocardial infarction, or
urgent revascularization 2 years after contemporary
PCI+MT to MT alone in stable CAD

4. FAME 2 Inclusion Criteria
Referred for PCI because of
Stable angina pectoris (CCS 1, 2, 3)
Stabilized angina pectoris CCS class 4
Atypical or no chest pain with documented
ischemia
And
Angiographic 1, 2, or 3 vessel disease

5. FAME 2 Exclusion Criteria
Prior CABG
LVEF < 30%
LM disease

6. FAME 2 Primary End Point
Composite of
all cause death
myocardial infarction
unplanned hospitalization with urgent revascularization

7. FAME 2 Study Centers (n=28)
Investigators
Centers
# of Patients
Piroth
Hungarian Institute of Cardiology- Hungary
145
Jagic
Clinical Center Kragujevac- Serbia
132
Mobius-Winkler
Heart Center Leipzig- Germany
131
Pijls
Catherina-Ziekenhuis- The Netherlands 89
Rioufol
Hospices Civil de Lyon- France 86
Witt
Sodersjukhuset- Sweden 85
De Bruyne
Cardiovascular Center Aalst- Belgium 82
Kala
University Hospital Brno- Czech Republic 75
Fearon
Stanford Univ/VA Med Center Palo Alto- USA 50
MacCarthy
Kings College Hospital- UK 42
Engstroem
Rigshospitalet University Hospital- Denmark
Oldroyd
Golden Jubilee National Hospital- UK 37
Mavromatis
Atlanta VA Medical Center- USA 34
Manoharan
Royal Victoria Hospital- Ireland 27

8. FAME 2 Study Centers (n=28)
Investigators
Centers
# of Patients
Ver Lee
Northeast Cardiology Associates- USA 25
Frobert
Orebro University Hospital- Sweden
Curzen
Southampton General Hospital- UK 18
Sohn
Klinikum der Universitat Munchen- Germany
Uren
Edinburgh Heart Center- Scotland 12
Samady
Emory University- USA
Dambrink
Isala Klinieken- Netherlands
Mansour
CHUM - Hotel Dieu- Canada 11
Arain
Tulane University- USA 8
Mates
Nemocnice Na Homolce- Czech Republic
Rensing
St. Antonius Ziekenhuis- Netherlands 5
Valgimigli
Universitaria de Ferrara- Italy 4
Rieber
Heart Center Munich- Germany 3
Schampaert
Hopital du Sacre Coeur- Canada 2

9. DSMB Recommendation
On recommendation of the independent Data and Safety Monitoring Board* recruitment was halted on January 15th, 2012 after inclusion of 1220 patients (± 54% of the initially planned number of randomized patients)
*DSMB: Stephan Windecker, Chairman, Stuart Pocock, Bernard Gersh

10. Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI
FAME 2 Flow Chart
Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI
N = 1220
FFR in all target lesions
Randomized Trial
73%
Registry
50% randomly
assigned to FU
27%
At least 1 stenosis
with FFR ≤ 0.80 (n=888)
Randomization 1:1
PCI + MT MT
When all FFR > 0.80
(n=332) MT
Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years

11. FAME 2 Baseline Clinical Characteristics (1)
Randomized trial N=888
Registry N=322 P*
 Patients, N
PCI+MT=447
MT=441
with FU=166
Demographic
Age (y)
64±9
64±10
 0.89
Male sex - (%)
79.6
76.6
68.1
0.006
BMI
28.3±4.3
28.4±4.6
27.8±3.9
0.14
Risk factors for CAD
Positive family history CAD - (%) 49
47  46
0.60
Smoking - (%) 20
20  21
 0.79
Hypertension - (%) 78 83
0.21
Hypercholesterolemia - (%) 74 80 73
0.15
Diabetes mellitus - (%) 28 27 25
0.65
*P value compares all RCT patients with patients in registry

12. Baseline Clinical Characteristics (2)
Randomized trial N=888
Registry N=322 P*
 Patients, N
PCI+MT=447
MT=441
with FU=166
Non-Cardiac Co-Morbidity
Renal Failure (Cr > 2.0 mg/dL) - (%) 2 3
0.14
History of stroke or TIA - (%) 8 7 6
0.52
Peripheral vascular disease - (%) 10 11 5
0.03
Cardiac History
History of MI - (%) 38 39
0.92
History of PCI in target vessel -(%) 18 17 21
0.36
Angina - (%)
0.60
Asymptomatic 12
CCS class I 22 25
CCS class II 46 45
CCS class III 15 14
CCS class IV, stabilized
Silent ischemia- (%) 16
0.93
LVEF < 50% - (%) 20
0.70
*P value compares all RCT patients with patients in registry

13. Angiographic Characteristics
Randomized trial N=888
Registry N=322 P*
 Patients, N
PCI+MT=447
MT=441
with FU=166
Angiographically significant stenoses - no. per patient
1.87±1.05
1.76±0.98
1.34±0.60
<0.001
No of vessels with ≥ 1 significant stenoses - (%) 1 56 59 78 2 35 33 18 3 9 8
Prox- or mid- LAD stenoses - (%) 65 63 45
*P value compares all RCT patients with patients in registry

14. FFR Measurements Randomized trial N=888 Registry N=322 P* Patients, N
Randomized trial N=888
Registry N=322 P*
 Patients, N
PCI+MT=447
MT=441
with FU=166
FFR significant stenoses -
no. per patient
1.51±0.78
1.43±0.73
0.03±0.17
<0.001
No of vessels with ≥ 1 significant stenoses (by FFR) - (%) 1 74 78
3.0 2 23 19 3
Prox- or mid- LAD stenoses - (%) 62 59
Lesions with FFR ≤ (%) 76
2 **
Mean FFR in stenoses with FFR ≤ 0.80
0.64±0.13
0.64±0.14
0.50±0.00
0.01
* P value compares all RCT patients with patients in registry
** Chronic occlusions in the registry patients were arbitrarily assigned an FFR value of These patients also had another lesion >50% with an FFR >0.80.

15. FAME 2 Primary Outcomes 20 15 Cumulative incidence (%) 10 5 2 4 6 8 10
PCI+MT vs. MT: HR 0.39 (95% CI ) P<0.001
PCI+MT vs. Registry: HR 0.90 (95% CI ) P=0.72
MT vs. Registry: HR 2.34 (95% CI ) P=0.002
MT alone
Registry
PCI+MT 15
Cumulative incidence (%) 10 5 2 4 6 8 10 12 14 16 18 20 22 24
Months after randomization
No. at risk MT
441
417
398
389
379
369
362
360
359
355
353
351
297
PCI+MT
447
434
429
426
425
420
416
414
410
408
405
403
344
Registry
166
164
162
160
157
157
156
153
151
150
150
150
122

16. Landmark Analysis for Urgent Revascularization
FAME 2
Landmark Analysis for Urgent Revascularization 5 10 15 20
Cumulative incidence (%) 2 4 6 8 12 14 16 18 22 24
Months after randomisation .5 1
1.5 2
2.5
Cumulative incidence (%) 3 4 5 6 7
Days after randomisation
0-7days: HR 0.49 (95%CI )
8 days-2years: HR 0.21 (95%CI )
P for interaction=0.34
PCI+MT vs MT
PCI+MT
MT alone

17. Landmark Analysis for Death or Myocardial Infarction
FAME 2
Landmark Analysis for Death or Myocardial Infarction 5 10 15 20
Cumulative incidence (%) 2 4 6 8 12 14 16 18 22 24
Months after randomisation
0-7days: HR 9.01 (95%CI )
8 days-2years: HR 0.56 (95%CI )
P for interaction 0.002
PCI+MT vs MT .5 1
1.5 2
2.5
Cumulative incidence (%) 3 4 5 6 7
Days after randomisation
PCI+MT
MT alone

18. Urgent AND Non-Urgent Revascularizations
FAME 2
Urgent AND Non-Urgent Revascularizations 40
PCI+MT vs. MT: HR 0.16 (95% CI ) P<0.001 35
MT alone
PCI+MT 30 25
Cumulative incidence (%) 20 15 10 5 2 4 6 8 10 12 14 16 18 20 22 24
Months after randomization
No. at risk MT
441
389
360
337
315
302
290
277
272
268
260
254
218
PCI+MT
447
440
434
429
427
422
417
410
407
406
402
399
343
After 2 years, > 40% of patients treated by MT had
crossed over i.e. had undergo any revascularisation

19. Urgent revascularisations according to
FAME 2
Urgent revascularisations according to
different triggers for the revascularisation
Months after Revascularisation 4 8 12 16 20 24
PCI + MT
MT alone
Cumulative Urgent Revascularization
Events per 100 patients-years
Urgent revascularisation was triggered in > 80% by an MI,
by dynamic ST changes, or by resting angina

20. Total Revascularisations
FAME 2 Symptoms
Baseline
PCI+MT
MT alone
Registry
30 Days
6 Months
12 Months
24 Months 20 40
Patients with CCS II to IV (%) 5 10 15 20 25 30 35 40
Cumulative incidence (%)
166
165
162
160
157
156
153
149
144
142
141
116
Registry
447
440
434
429
427
422
417
410
407
406
402
399
343
PCI+MT
441
389
360
337
315
302
290
277
272
268
260
254
218 MT
No. at risk 2 4 6 8 12 14 16 18 22 24
Months after randomization
MT vs. Registry: HR 4.26 (95% CI ) P<0.001
PCI+MT vs. Registry: HR 0.66 (95% CI ) P=0.13
PCI+MT vs. MT: HR 0.16 (95% CI ) P<0.001
Total Revascularisations

21. FAME 2 Conclusions
1. More than 25% of stable CAD patients scheduled for PCI on the
basis of clinical and angiographic data, have no stenosis with an
FFR<0.80. These patients have a favorable outcome with MT
alone.
2. The rate of death, MI, or urgent revascularization at 2 years in
patients with stable CAD treated with FFR-guided PCI with new
generation drug-eluting stents was less than half than in patients
treated with MT alone.
3. Beyond 7 days from randomisation, PCI plus MT significantly
reduces the rate of death or MI when compared to MT alone.

22. FAME 2
Accepted for publication in the NEJM, September 2, 2014