Transcript Slide 1

Fractional Flow Reserve–Guided PCI
for Stable Coronary Disease
FAME 2
Report of the Primary Endpoint
Clinicaltrials.gov NCT01132495
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
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
FAME 2 Background
• 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
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
FAME 2 Exclusion Criteria
1. Prior CABG
2. LVEF < 30%
3. LM disease
FAME 2 Primary End Point
Composite of
• all cause death
• myocardial infarction
• unplanned hospitalization with urgent
revascularization
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
42
Oldroyd
Golden Jubilee National Hospital- UK
37
Mavromatis
Atlanta VA Medical Center- USA
34
Manoharan
Royal Victoria Hospital- Ireland
27
7
FAME 2 Study Centers (n=28)
Investigators
Centers
# of Patients
Ver Lee
Northeast Cardiology Associates- USA
25
Frobert
Orebro University Hospital- Sweden
25
Curzen
Southampton General Hospital- UK
18
Sohn
Klinikum der Universitat Munchen- Germany
18
Uren
Edinburgh Heart Center- Scotland
12
Samady
Emory University- USA
12
Dambrink
Isala Klinieken- Netherlands
12
Mansour
CHUM - Hotel Dieu- Canada
11
Arain
Tulane University- USA
8
Mates
Nemocnice Na Homolce- Czech Republic
8
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
8
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
9
FAME 2 Flow Chart
Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI
N = 1220
FFR in all target lesions
Registry
Randomized Trial
At least 1 stenosis
with FFR ≤ 0.80 (n=888)
When all FFR > 0.80
(n=332)
Randomization 1:1
PCI + MT
MT
73%
MT
27%
Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years
50% randomly
assigned to FU
FAME 2 Baseline Clinical Characteristics (1)
Randomized trial N=888
Patients, N
Registry N=322
P*
PCI+MT=447
MT=441
with FU=166
64±9
79.6
28.3±4.3
64±10
76.6
28.4±4.6
64±10
68.1
27.8±3.9
0.89
0.006
0.14
49
20
78
74
28
47
20
78
80
27
46
21
83
73
25
0.60
0.79
0.21
0.15
0.65
Demographic
Age (y)
Male sex - (%)
BMI
Risk factors for CAD
Positive family history CAD - (%)
Smoking - (%)
Hypertension - (%)
Hypercholesterolemia - (%)
Diabetes mellitus - (%)
*P value compares all RCT patients with patients in registry
11
Baseline Clinical Characteristics (2)
Randomized trial N=888
Patients, N
Non-Cardiac Co-Morbidity
Renal Failure (Cr > 2.0 mg/dL) - (%)
History of stroke or TIA - (%)
Peripheral vascular disease - (%)
Cardiac History
History of MI - (%)
History of PCI in target vessel -(%)
Angina - (%)
Asymptomatic
CCS class I
CCS class II
CCS class III
CCS class IV, stabilized
Silent ischemia- (%)
LVEF < 50% - (%)
Registry N=322
P*
PCI+MT=447
MT=441
with FU=166
2
8
10
3
7
11
3
6
5
0.14
0.52
0.03
38
18
39
17
38
21
0.92
0.36
0.60
12
18
46
18
6
16
20
10
22
45
15
8
17
14
10
25
45
14
6
16
18
*P value compares all RCT patients with patients in registry
0.93
0.70
12
Angiographic Characteristics
Randomized trial N=888
PCI+MT=447 MT=441
Patients, N
Angiographically significant
stenoses - no. per patient
No of vessels with ≥ 1 significant
stenoses - (%)
1
2
3
Prox- or mid- LAD stenoses - (%)
1.87±1.05
1.76±0.98
Registry N=322
with FU=166
P*
1.34±0.60
<0.001
<0.001
56
35
9
59
33
8
78
18
3
65
63
45
*P value compares all RCT patients with patients in registry
<0.001
13
FFR Measurements
Randomized trial N=888
PCI+MT=447
MT=441
Patients, N
FFR significant stenoses no. per patient
Registry N=322
with FU=166
P*
<0.001
1.51±0.78
1.43±0.73
0.03±0.17
74
23
3
78
19
3
3.0
0
0
Prox- or mid- LAD stenoses - (%)
62
59
0
<0.001
Lesions with FFR ≤ 0.80 - (%)
76
76
2 **
<0.001
0.64±0.13
0.64±0.14
0.50±0.00
0.01
No of vessels with ≥ 1 significant
stenoses (by FFR) - (%)
1
2
3
Mean FFR in stenoses with FFR ≤ 0.80
* P value compares all RCT patients with patients in registry
** Chronic occlusions in the registry patients were arbitrarily assigned an FFR value of 0.50. These patients also had another
lesion >50% with an FFR >0.80.
14
FAME 2 Primary Outcomes
Cumulative incidence (%)
20
PCI+MT vs. MT:
HR 0.39 (95% CI 0.26-0.57) P<0.001
PCI+MT vs. Registry: HR 0.90 (95% CI 0.49-1.64) P=0.72
MT vs. Registry:
HR 2.34 (95% CI 1.35-4.05) P=0.002
15
PCI+MT
MT alone
Registry
10
5
0
0
No. at risk
MT
441
PCI+MT
447
Registry
166
2
4
6
8
417
434
164
398
429
162
389
426
160
379
425
157
10
12
14
16
Months after randomization
369
420
157
362
416
156
360
414
153
359
410
151
18
20
22
24
355
408
150
353
405
150
351
403
150
297
344
122
FAME 2
Landmark Analysis for Urgent Revascularization
2.5
Cumulative incidence (%)
Cumulative incidence (%)
20
15
PCI+MT vs MT
0-7days:
HR 0.49 (95%CI 0.09-2.70)
8 days-2years: HR 0.21 (95%CI 0.12-0.37)
2
P for interaction=0.34
1.5
1
.5
PCI+MT
0
0
1
2
3
4
5
6
Days after randomisation
MT alone
7
10
5
0
0
2
4
6
8
10
12
14
16
Months after randomisation
18
20
22
24
FAME 2
Landmark Analysis for Death or Myocardial Infarction
Cumulative incidence (%)
20
Cumulative incidence (%)
PCI+MT vs MT
2.5
15
0-7days:
HR 9.01 (95%CI 1.13-72.0)
8 days-2years: HR 0.56 (95%CI 0.32-0.97)
P for interaction 0.002
2
1.5
PCI+MT
MT alone
1
.5
0
0
1
2
3
4
5
6
Days after randomisation
7
10
5
0
0
2
4
6
8
10
12
14
16
Months after randomisation
18
20
22
24
FAME 2
Urgent AND Non-Urgent Revascularizations
40 PCI+MT vs. MT:
HR 0.16 (95% CI 0.11-0.22) P<0.001
Cumulative incidence (%)
35
PCI+MT
30
MT alone
25
20
15
10
5
0
0
No. at risk
MT
441
PCI+MT
447
2
4
6
8
389
440
360
434
337
429
315
427
10
12
14
16
Months after randomization
302
422
290
417
277
410
272
407
18
20
22
24
268
406
260
402
254
399
218
343
After 2 years, > 40% of patients treated by MT had
crossed over i.e. had undergo any revascularisation
Cumulative Urgent Revascularization
Events per 100 patients-years
FAME 2
Urgent revascularisations according to
different triggers for the revascularisation
MT alone
PCI + MT
24
20
16
12
8
4
0
0
4
8
12
16
20
Months after Revascularisation
24 0
4
8
12
16
20
Months after Revascularisation
Urgent revascularisation was triggered in > 80% by an MI,
by dynamic ST changes, or by resting angina
24
FAME 2 Symptoms
Baseline
PCI+MT
MT alone
Registry
30 Days
PCI+MT
MT alone
Registry
Total Revascularisations
40
6 Months
35
MT alone
30
Cumulative incidence (%)
PCI+MT
Registry
12 Months
PCI+MT
MT alone
PCI+MT vs. MT:
HR 0.16 (95% CI 0.11-0.22) P<0.001
PCI+MT vs. Registry: HR 0.66 (95% CI 0.38-1.14) P=0.13
MT vs. Registry:
HR 4.26 (95% CI 2.66-6.81) P<0.001
25
20
15
10
Registry
5
0
24 Months
PCI+MT
0
2
4
6
8
441
447
166
389
440
165
360
434
162
337
429
160
315
427
157
10
12
14
Months after randomization
16
18
20
22
24
272
407
144
268
406
142
260
402
141
254
399
141
218
343
116
No. at risk
MT
PCI+MT
Registry
MT alone
Registry
0
20
40
Patients with CCS II to IV (%)
302
422
156
290
417
153
277
410
149
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.
FAME 2
Accepted for publication in the NEJM, September 2, 2014