F NCT03187639 on behalf of the FORECAST Investigators. on behalf - - PowerPoint PPT Presentation

16/10/2020

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Tomography Coronary Tomography Coronary A

Angiography in the Assessment &

ngiography in the Assessment & Management of Management of St

St able Chest Pain

able Chest Pain

N Curzen N Curzen , Z Nicholas, B Stuart, S Wilding, K Hill, J Shambrook, Z Eminton, D Ball, C Barrett, L Johnson, , Z Nicholas, B Stuart, S Wilding, K Hill, J Shambrook, Z Eminton, D Ball, C Barrett, L Johnson, J Nuttall, K Fox, D Connolly, P O’Kane, A Hobson, A Chauhan, N Uren, G McCann, C Berry, J Carter, J Nuttall, K Fox, D Connolly, P O’Kane, A Hobson, A Chauhan, N Uren, G McCann, C Berry, J Carter, C Roobottom, M Mamas, R Rajani, I Ford, P Douglas, M Hlatky C Roobottom, M Mamas, R Rajani, I Ford, P Douglas, M Hlatky

• n behalf of the FORECAST Investigators.
• n behalf of the FORECAST Investigators.

NCT03187639 NCT03187639

16/10/2020

Conflicts of Interest

FORECAST is an investigator-initiated trial NC applied for & was awarded an unrestricted research grant from HeartFlow … The company had no formal role in the design, prosecution, data collection, analysis of the trial The sponsor for FORECAST is R&D Department, University Hospital Southampton NHS FT NC has received speaker fees and travel sponsorship from HeartFlow in the last 3 years

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BACKGROUND

§ There is wide variation in practice in the

assessment of stable new onset chest pain

§ There is value in determining the presence of both atheroma (anatomy) & ischaemia (physiology)… § Most commonly used tests focus on only 1 of these parameters § FFR CT is a well validated test that provides both anatomical &

physiological information non-invasively

1-3

§ FFR CT utilises the output from CTCA & derives FFR in major epicardial vessels using FD & 3D modelling

1J Am Coll Cardiol . 2011;58(19):1989-1997 2 JAMA. 2012;308(12):1237-1245 3 J Am Coll Cardiol . 2014;63(12):1145-1155

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BACKGROUND 2

§ In the PLATFORM study

4, CTCA with FFR CT resulted in a 61% reduction in the need for ICA compared with routine care

§ In a prespecified economic analysis of PLATFORM

5, CTCA+FFR CT was associated with

significantly lower cost than routine care in the cohort assigned to ICA, but not in the cohort assigned to non-invasive assessment

§ In FFR CT RIPCORD 6, the availability of FFR

CT led to a change in management in 36% of 200 cases cf CTCA alone

§ In the ADVANCE Registry 7, the rate of unobstructed coronaries at ICA was 14.4% in patients with FFR

CT <0.8 vs.

43.8% in those with FFR

CT>0.8 (p<0.001)

§ In the UK, NICE Technology Appraisal

8

4 Eur Heart J . 2015;36(47):3359-3367 7 Eur Heart J . 2018;39(41):3701-3711 6 JACC Cardiovasc Imaging

. 2016;9(10):1188-1194

5 J Am Coll Cardiol . 2015 Dec 1;66(21):2315-23 8 NICE Medical Technologies Guidance MTG32, Feb 2017

No randomized trial has compared FFR

CT with routine assessment

as the initial testing strategy

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TRIAL RATIONALE:

Why is resource utilisation the primary endpoint? Previous data suggest that FFR Previous data suggest that FFR

CT CT will reduce ICA without increased rates

will reduce ICA without increased rates

• f death, MI or revascularisation…
• f death, MI or revascularisation…

BUT: BUT: will it be cost effective as an initial strategy in patients with

will it be cost effective as an initial strategy in patients with stable chest pain? stable chest pain? § Evidence so far from non-randomized clinical studies suggests that FFR

CT:

• reduces rate of ICA & reduces ICA showing no significant CAD
• is associated with lower costs… ? But only in those allocated to an invasive strategy?
• is not associated with an increase in ischaemic events in the FFR

CT patient cohorts (ie it is SAFE)

§ NICE recommends CTCA+FFR

CT as a frontline test that is clinically effective and will save money

§ NHS Innovation & Technology Payment Scheme invests in FFR

CT for front line clinical practice

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STUDY HYPOTHESIS & PRIMARY OBJECTIVE To determine whether, in a population of patients presenting to Rapid Access Chest Pain Clinics (RACPC) in the To determine whether, in a population of patients presenting to Rapid Access Chest Pain Clinics (RACPC) in the UK, routine CTCA+FFR UK, routine CTCA+FFR CT

CT as a default test is superior, in terms of

as a default test is superior, in terms of resource utilisation resource utilisation , , when compared with routine clinical pathway algorithms recommended by NICE CG95 when compared with routine clinical pathway algorithms recommended by NICE CG95 STUDY SECONDARY OBJECTIVES 1. To compare clinical outcomes between the 2 groups at 9 months 2. To compare the effect on general wellbeing between the 2 groups at 9 months Sample Size Calculation Based upon PLATFORM cost analysis… randomizing 700 patients in each group would provide 90% power to detect 20% difference in costs

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METHOD

• Randomised controlled trial
• 1400 patients attending RACPC in 11 UK centres

Primary Endpoint: Resource Utilisation at 9 months

• non-invasive cardiac tests
• invasive angiography
• revascularization
• hospitalization for cardiac event
• cardiac meds
• outpatient attendances

Secondary Endpoints : Clinical

• MACCE (All cause mortality, non fatal MI, CVA)
• Death + MI + CVA + unplanned revasc + cardiac hospitalization
• Requirement for non-invasive cardiac tests
• Requirement for ICA
• procedural complications

Secondary Endpoints : QOL/Health

• QOL
• Patient satisfaction
• angina status
• time to definitive management plan
• time to completion of initial management plan

Inclusion Criteria

• age >18 yrs
• chest pain deemed to require investigation

Exclusion Criteria

• unstable angina or ACS
• prior PCI/CABG
• new onset AF
• contraindications to CTCA
• prosthetic valve
• life expectancy<12 months

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METHOD 2

“Those patients with a coronary stenosis of >40% in at least one major epicardial vessel of stentable/graftable diameter will be referred for FFR

CT.

(NB Lesions in distal vessels beyond the reach of stents or grafts or vessels of a diameter not suitable for stenting/grafting will not qualify for FFR

CT if there are no other

more significant lesions ).“

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RESULTS: CONSORT & DEMOGRAPHICS

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RESULTS

N=699

Test Arm

FFR CT performed? Yes 220 (31.5%) No 479 (68.5%) Reason not performed? No CTCA done 25 (5.2%) No lesion >40% 415 (86.6%) Not analysable 39 (8.2%) Any FFR CT <0.8 57.3% FFR CT result used in Mx plan? 98.2% ICA after FFR

CT?

100 (45.5%) Non-invasive test after FFR

CT?

14 (6.4%) Initial Tests Undertaken

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RESULTS: 9 month tests & revascularisation

§ 14% lower total ICA in test vs. reference group

(p=0.02)

§ 22% fewer patients had ICA in test vs reference group

(p=0.01)

Data are numbers of tests (number of patients)

66% 96%

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RESULTS: PRIMARY ENDPOINT

TOTAL CARDIAC COSTS TOTAL CARDIAC COSTS

RESULTS: SECONDARY CLINICAL ENDPOINT

MACCE/CLINICAL EVENTS

• Metastatic lung Ca
• Community acquired

pneumonia

Reference Group Test Group

RESULTS: SECONDARY CLINICAL ENDPOINT

QoL/Angina status

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LIMITATIONS § The cut off for sending patients for FFR

CT of > 40% stenosis was

pragmatic § The proportion of patients in the Reference arm undergoing CTCA increased through the recruitment period, as anticipated from CG95 NICE guidelines, but at a rate of rise that was impossible to model at the start of the trial

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CONCLUSION In patients presenting with new onset stable CP, a strategy of CTCA with FFR In patients presenting with new onset stable CP, a strategy of CTCA with FFR

CT CT,

, when compared with a strategy of routine care: when compared with a strategy of routine care: ü ü d d id not id not significantly reduce costs in the NHS system significantly reduce costs in the NHS system ü ü is associated with a significantly lower rate of invasive angiography (22%) is associated with a significantly lower rate of invasive angiography (22%) ü ü is not is not associated with significantly different rates of associated with significantly different rates of MACCE or revascularisation MACCE or revascularisation

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ACKNOWLEDGEMENTS

Site PI Main RN contact Birmingham Birmingham Dr Derek Connolly Ashley Turner Blackpool Blackpool Prof Anoop Chauhan Stephen Preston Bournemouth Bournemouth Dr Peter O’Kane Nicki Wells Edinburgh Edinburgh Prof Neal Uren Belinda Rif Glasgow Glasgow Prof Colin Berry Andrew Dougherty Leicester Leicester Prof Gerry McCann Debbie Lee (CRP) North Tees North Tees Dr Justin Carter Julie Quigley Plymouth Plymouth Prof Carl Roobottom Julie Alderton Portsmouth Portsmouth Dr Alex Hobson Charlotte Turner Southampton Southampton Prof Nick Curzen Zoe Duke Stoke Stoke Prof Mamas Mamas Ian Massey

Zoe Nicholas – Project Manager Coronary Research Group, UHS

Trial Steering Committee

Prof K Fox (Chair) Prof I Ford (statistics) Prof Pam Douglas Dr Ronak Rajani Mr J Mostyn (Patient rep) Mrs B Stuart (Senior Trial Statistician, CTU) Mrs Z Eminton (CTU) Mr D Ball (CTU) Miss Z Nicholas (Project Manager) Co-opted: Prof N Curzen (Chief Investigator)

Trial Management Committee

Prof N Curzen (Chair) Z Eminton (CTU) D Ball (CTU) Miss Z Nicholas (Project Manager) B Stuart (Senior Trial Statistician, CTU) S Wilding (Statistician, CTU) L Johnson (Trial data Coordinator, CTU) Prof Colin Berry (co-PI) Mr I Harris (Patient Rep) Prof M Hlatky (Resource Utilisation Model) Prof A Zaman K Hill, (Statistician, CTU) Dr A Cook (Public Health, CTU) Research& Development

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Reserve Slides

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