Real-world clinical utility and impact on clinical decision making of - - PowerPoint PPT Presentation

Real-world clinical utility and impact on clinical decision making of FFRCT Lessons from the ADVANCE Registry

Dr Tim Fairbairn on behalf of the ADVANCE investigators Nieman K, Akasaka T , Norgaard BL, Berman DS, Raff G , Hurwitz-Koweek LM, Pontone G, Kawasaki T, Sand NP, Jensen J, Amano T, Poon M, Ovrehus K, Sonck J, Rabbat M, Mullen S, De Bruyne B, Rogers C, Matsuo H, Bax JJ, Leipsic J, Patel MR

Disclosures

• Dr. Fairbairn: HeartFlow Speakers bureau
• Full author Disclosures available online (European Heart Journal)
• The ADVANCE Registry was funded by HeartFlow Inc., via individual Clinical Study

Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events

Coronary CTA For Assessment of Chest pain

Coronary CT Angiography (CCTA)

• Increasingly used as primary diagnostic strategy for assessment of chest pain with

suspected CAD

• High sensitivity but modest specificity
• Improves patient outcomes compared to functional testing
• High rates of invasive coronary angiography showing non-obstructive coronary disease

and increased rates of revascularisation

• Cannot guide revascularization alone owing to the lack of functional information

Anatomical Testing Functional Testing Anatomical and Functional

Imaging in Coronary Artery Disease

Coronary CT angiography FFRCT Treadmill ECG Stress Echo Stress MRI SPECT

CT Derived Fractional Flow Reserve (FFRCT)

Improves discrimination of ischemia Reduces ICA showing non-obstructive disease Increases appropriate revascularisations Cost saving

Packard et al, EHJ CvImaging 2016 Hlatky et al, JACC, 2015 Douglas et al, EHJ 2015 Driessen et al, EuroPCR 2018

ADVANCE Registry

• 5083 subjects undergoing CCTA with clinically stable symptoms were

prospectively enrolled at 38 sites in Europe, North American and Japan between July 2015 – October 2017

• Primary Endpoint:

– Reclassification rate between CCTA-based versus FFRCT-based management plans as determined by blinded core laboratory adjudication

• Secondary endpoints:

– Reclassification rate between CCTA-based and FFRCT-based management by site adjudication – Incidence of ICA demonstrating no obstructive coronary stenosis >50% – 90-day survival free from all cause or major adverse cardiovascular events (MACE) inclusive of MI, all-cause mortality or unplanned hospitalization for ACS leading to revascularization* * Event adjudication performed by independent Clinical Events Committee

Planned and Actual Management

Management Plan

Separate site and blinded core lab interpretation and recommendations

• Primary management plan based on

CCTA alone

• Second ‘revised’ management plan

based on CCTA + FFRCT

• Actual Management at 90-days

Treatment Strategies

• 1. Medical Treatment
• 2. PCI
• 3. CABG
• 4. Further testing

FFRCT pathway and Patient Demographics

Patients recruited 5083 FFRCT requested 4893 (96.2%) FFRCT analysed 4737 (96.8%) CCTA not submitted for FFRCT 190 (3.7%) Not analysable 156 (3.2%)

FFRCT patient pathway Population Demographics

FFRCT (n=4737)

Age (years) 66.1 (±10.3) Male sex 3134 (66.2%) Hypertension 2835 (59.8%) Diabetes Mellitus 1037 (21.9%) Hyperlipidaemia 2753 (58.1%) Angina status Atypical Typical Non-cardiac pain Dyspnoea None Unknown 1727 (36.5%) 1025 (21.6%) 297 (6.3%) 472 (10.0%) 1164 (24.6%) 52 (1.1%) Diamond-Forrester Risk 51.6 (±20.3)

Disease Burden

>50% stenosis: 72.1% >50% stenosis (multivessel): 36.9% Ischaemia (FFRCT ≤0.80): 66.4% Median FFRCT 0.79 Median FFRCT 0.88 Median FFRCT 0.87

LAD RCA LCX

Reclassification by Core Lab

Post CCTA Management Strategy (n=4715)β

β 22 post CCTA treatment recommendations were not made * 924 (19.8%) had ICA and no revascularization

66.9% reclassification

Actual Management* (n=4737) Post FFRCT Management Strategy (n=4715)β

Reclassification by Site

Post CCTA Management Strategy (n=4119)β

β 618 post CCTA treatment recommendations were not made * 924 (19.8%) had ICA and no revascularization

Post FFRCT Management Strategy (n=4119) β

63.5% reclassification

Actual Management* (n=4737)

FFRCT Stratum

90 day Clinical Outcomes Rate of ICA, Non-Obstructive CAD and Revascularization

ICA 40% Non-obstructive CAD 14.4%* ICA 19% Non-obstructive CAD 43.8%* * No coronary stenosis ≥50% by site interpretation of ICA

90 day Clinical Outcomes MACE (MI, Death, Hospital Admission for ACS and Unplanned Revascularization)

Days Days All MACE

FFRCT ≤ 0.80 FFRCT > 0.80

Death or MI

FFRCT ≤ 0.80 FFRCT > 0.80

Days

P=0.0019 HR: 19.75 (1.19-326) P=0.0077 HR: 14.68 (0.88-246)

n=3145 n=1592 n=3145 n=1592

Limitations

• Registry study – cannot exclude inclusion bias that affects all registries

– ‘Real world’

• Selection bias; small percentage (6.8%) not submitted or not analyzable

– No difference in groups demographics

• Enrolled subjects with CAD on CTA

– This is the relevant population for FFRCT

• Multifaceted nature of clinical decision making

– CCTA alone vs. CCTA + FFRCT, Symptom severity, anatomical location of stenosis, local practice

• Only early follow up (90 days)

– Further follow up planned at 1 and 3 years

Summary

In an international multicenter real-world population of

• ver 5000 patients, the addition of FFRCT to CCTA:
• Changed management plans in over 60% of subjects
• Was associated with low rates of invasive angiography, and

good safety when FFRCT >0.80 (no MACE)

• Significantly lowered the rate of anatomical (<50% DS) non-
• bstructive disease at ICA (14 vs 44%) with abnormal FFRCT
• An inverse relationship exists between FFRCT value and

likelihood of downstream ICA, revascularization, and MACE