The BHF FAMOUS NSTEMI Trial For the FAMOUS NSTEMI Investigators ESC Hotline for Myocardial Infarction, 1 Sep 2014 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

Body text Disclosures British Heart Foundation Project Grant. 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 ESC Hotline 1 Sep 2014 Ischaemia hypothesis = Lesion-level ischaemia predicts coronary risk. FFR ischaemic threshold = 0.80 specifies OMT vs. PCI vs. CABG FFR - Unnecessary PCIs and procedure- related MI will be reduced. The validity of FFR in culprit and non- culprit arteries is uncertain.

Berry C et al Am Heart J 2013; NCT 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. 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 Southampton Freeman Royal Blackburn Sunderland

Screened Consent Screened n = 444 Oct May 2013 n = 174 n = Randomise ESC Hotline 1 Sep 2014 Registry n = 503

GRACE Score for Death/MI 6 months = 146 Time from event to angiography 3 (2,5) days Radial access – 90% % Baseline characteristics ESC Hotline 1 Sep 2014

FFR vs. Stenosis Severity Stenosis severity, % 350 patients 706 lesions ≥ 30% severity FFR successful 100% of patients >99% lesions 2 wire dissections FFR

FFR-disclosure Treatment change Initial treatment Change post-FFR Final decision FFR treatment change ~ 22% of patients

Primary outcome % medical therapy at baseline % p = p = In-hospital costs were similar ESC Hotline 1 Sep 2014

% medical therapy only Baseline & 1 year % p = p = Quality of life was similar ESC Hotline 1 Sep 2014

All MACE FFR-guided vs. Angio-guided Angiography – guided n = 15 (8.6%) MACE 1 year FFR – guided n = 14 (8.0%) Log Rank p = 0.79 Days ESC Hotline 1 Sep 2014

Procedure-related MI FFR-guided vs. Angio-guided Type 4 - Procedure-related MI, 1 year Angiography - guided FFR - guided p = 0.12

Myocardial infarction FFR-guided vs. Angio-guided Type 4 MI Procedure-related Types 1-3 MI Spontaneous Angiography - guided FFR - guided Angiography - guided p = 0.12 p = 0.56

Summary 1.Trial pop n 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.

Thank you. Patients, staff, funders. FAMOUS-NSTEMI European Heart Journal 1 Sept on-line Clinical Event Committee Dr Andrew Hannah, Dr Andrew Stewart Data & Safety Monitoring Committee Prof John Norrie, Prof Andrew Clark, Dr Saqib Chowdhary