The BHF FAMOUS NSTEMI Trial

For the FAMOUS NSTEMI InvestigatorsESC 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

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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

Standard careAnatomy vs. Anatomy + Function

• Urgent diagnostic angiography Treatment decisions for OMT, PCI & CABG 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 CABG vs. PCI vs. medical therapy (OMT)

• FFR in angina – Optimises the PCI strategy, and reduces procedure-related MIs & MACE.

• FFR in NSTEMI - Validity of FFR in culprit & non-culprit arteries is uncertain.

Berry C et al Am Heart J 2013; NCT01764334

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-NSTEMIOutcomes

• Primary outcomeThe proportion of patients allocated to medical management only at baseline in each group.

• Secondary outcomes1. 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 lifeESC Hotline 1 Sep 2014

Golden Jubilee, GlasgowHairmyres

Southampton

Freeman

Royal Blackburn

Sunderland

Screened

Consent

Screenedn = 444

Oct. 2011

May 2013

n = 174n = 176

350Randomise

ESC Hotline 1 Sep 2014

Registryn = 503

0

20

40

60

80

100FFR-Guided Angiography-Guided

GRACE Score for Death/MI 6 months= 146

Time from event to angiography3 (2,5) days

Radial access – 90%

%

Baseline characteristics350 randomised trial participants

ESC Hotline 1 Sep 2014

ESC Hotline 1 Sep 2014

FFR vs. Stenosis Severity

Stenosis severity, %

350 patients706 lesions≥ 30% severity

FFR successful100% of patients>99% lesions2 (0.03%) wire

dissections

FFR

FFR-disclosure- Impact on treatment plan

Initial treatment

Change post-FFR

Final decision

FFR treatment change ~ 22% of patients

Primary outcome% medical therapy only

0

5

10

15

20

25

Post-Randomisation 1-year

FFR-guided Angiography-guided

%

p = 0.022 p = 0.054

22.7

13.2

ESC Hotline 1 Sep 2014

% medical therapy onlyPost-randomisation & 1 year

0

5

10

15

20

25

Post-Randomisation 1-year

FFR-guided Angiography-guided

%

p = 0.022 p = 0.054

Costs and quality of life were similar ESC Hotline 1 Sep 2014

All MACEFFR-guided vs. Angio-guided

Angiography – guidedn = 15 (8.6%)

MACE1 year

FFR – guidedn = 14 (8.0%)

Log Rankp = 0.79

Days

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Procedure-related MIFFR-guided vs. Angio-guided

Angiography - guided

FFR - guided

p = 0.12

Type 4 MIProcedure-related

ESC Hotline 1 Sep 2014

Myocardial infarction typeFFR-guided vs. Angio-guided

Type 4 MIProcedure-related

Types 1-3 MISpontaneous

Angiography - guided

FFR - guided

FFR - guided

Angiography - guided

p = 0.12 p = 0.56

ESC Hotline 1 Sep 2014

Summary1. Trial popn represented > 40% of NSTEMI

patients who gave informed consent.

2. FFR was successful in 100% of patients

and safe (0.03% guidewire dissections).

3. Randomisation & adherence to protocol were successful.

4. FFR-disclosure commonly changed therapy, and reduced revascularisation & Type 4 MIs.

5. Health outcomes were similar.

Conclusions1. FFR is feasible & safe initially, and

optimises PCI in NSTEMI.

2. The trial was designed but not powered to assess health outcomes (no differences).

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. 2014 on-line

Clinical Event CommitteeDr Andrew Hannah, Dr Andrew Stewart

Data & Safety Monitoring CommitteeProf John Norrie, Prof Andrew Clark, Dr Saqib Chowdhary