The BHF FAMOUS
NSTEMI Trial
J. Layland, K.G. Oldroyd, N. Curzen, A. Sood, K.
Balachandran, R. Das, S. Junejo, N. Ahmed, M. Lee,
A. Shaukat, A. O'Donnell, J. Nam, A. Briggs, R.
Henderson, A. McConnachie, C. Berry
For the FAMOUS NSTEMI Investigators
ESC Hotline for Myocardial Infarction, 1 Sep 2014
Disclosures
British Heart Foundation Project Grant.
Body text
St
Jude Medical provided the pressure wires to the
6 hospitals that participated in this study.
Investigators: CB, NC, KGO are Consultants /
Speakers to St Jude Medical and/or Volcano Corp.
Institutional research agreement between St Jude
Medical and University of Glasgow / CB.
Travel support from Pfizer.
Natural history &
prognosis after NSTEMI
• Cardiac events
Coronary - Spontaneous plaque rupture
- Longer term remodelling
Myocardial - Sudden death & heart failure
• Non-cardiac events - co-morbidity
Decision-making
Anatomy vs. Anatomy + Function
• Ad hoc diagnostic angiography
Treatment decisions are based on
visual interpretation of the angiogram.
• FFR
Class I recommendation in stable CAD
No guideline recommendation in ACS,
evidence is lacking.
ESC Hotline 1 Sep 2014
Rationale: FFR in NSTEMI
• Ischaemia hypothesis =
Lesion-level ischaemia predicts coronary risk.
• FFR ischaemic threshold = 0.80
specifies OMT vs. PCI vs. CABG
• FFR - Unnecessary PCIs and procedurerelated MI will be reduced.
• The validity of FFR in culprit and nonculprit arteries is uncertain.
ESC Hotline 1 Sep 2014
FAMOUS-NSTEMI trial
• Hypothesis
Routine FFR is feasible in NSTEMI patients
and adds diagnostic, clinical and economic
benefits, compared to standard
angiography-guided management.
• Objective
Developmental trial for evidence-synthesis
to inform a definitive health outcome trial.
Berry C et al Am Heart J 2013; NCT01764334
ESC Hotline 1 Sep 2014
FAMOUS-NSTEMI
Outcomes
• Primary outcome
The proportion of patients allocated to medical
management only at baseline in each group.
• Secondary outcomes
1. Feasibility & safety of routine FFR.
2. Relationship of FFR vs. stenosis severity.
3. MACE – cardiac death, non-fatal MI, heart failure.
4. Resource use
5. Quality of life
ESC Hotline 1 Sep 2014
Golden Jubilee, Glasgow
Hairmyres
Freeman
Sunderland
Royal Blackburn
Southampton
Oct. 2011
Screened
May 2013
n = 176
Consent
Randomise
Screened
n = 444
Registry
n = 503
n = 174
350
ESC Hotline 1 Sep 2014
Baseline
characteristics
FFR-Guided
100
80
%
Angiography-Guided
GRACE Score for
Death/MI 6 months
= 146
40
Time from event to
angiography
3 (2,5) days
20
Radial access – 90%
60
0
ESC Hotline 1 Sep 2014
FFR vs. Stenosis Severity
350 patients
706 lesions
≥ 30% severity
FFR
FFR successful
100% of patients
>99% lesions
2 wire dissections
ESC Hotline 1 Sep 2014
Stenosis severity, %
FFR-disclosure
Treatment change
Initial
treatment
Change
post-FFR
Final
decision
FFR treatment change ~ 22% of patients
Primary outcome
% medical therapy at baseline
25
20
FFR-guided
Angiography-guided
22.7
%15
10
5
13.2
p = 0.022
In-hospital costs
were similar
p = 0.054
0
Post-Randomisation
1-year
ESC Hotline 1 Sep 2014
% medical therapy only
Baseline & 1 year
25
FFR-guided
Angiography-guided
20
%15
10
p = 0.022
p = 0.054
Post-Randomisation
1-year
5
0
ESC Hotline 1 Sep 2014
Quality of life was similar
All MACE
FFR-guided vs. Angio-guided
Log Rank
p = 0.79
MACE
1 year
Angiography – guided
n = 15 (8.6%)
FFR – guided
n = 14 (8.0%)
Days
ESC Hotline 1 Sep 2014
Procedure-related MI
FFR-guided vs. Angio-guided
Type 4 - Procedure-related MI, 1 year
p = 0.12
Angiography - guided
FFR - guided
Myocardial infarction
FFR-guided vs. Angio-guided
Type 4 MI
Procedure-related
p = 0.12
Types 1-3 MI
Spontaneous
p = 0.56
Angiography - guided
FFR - guided
FFR - guided
Angiography - guided
Summary
1. Trial popn represented > 40% of NSTEMI
patients who gave consent.
2. FFR was successful in 100% of patients
and safe (2 dissections in 706 lesions).
3. Randomisation & adherence to protocol
were successful.
4. FFR-disclosure commonly changed therapy,
 PCIs & Type 4 MIs and was cost neutral.
5. Health outcomes were similar.
Conclusions
1. FFR is feasible, safe and reduces PCI &
procedure MI in NSTEMI.
2. No difference in health outcomes vs.
standard care, but under-powered.
3. FFR-guided group outcomes
Most MACE not related to FFR disclosure.
Late MACE  Natural history of CAD progression.
4. A large trial is needed to assess health
outcomes & cost-effectiveness.
FAMOUS-NSTEMI
Thank you.
Patients, staff, funders.
Clinical Event Committee
Dr Andrew Hannah, Dr Andrew Stewart
Data & Safety Monitoring Committee
Prof John Norrie, Prof Andrew Clark, Dr Saqib Chowdhary
European Heart Journal 1 Sept. 2014 on-line