FAVOR III (Functional Assessment by Virtual Online Reconstruction). Comparison of quantitative flow ratio (QFR) and conventional pressure-wire based functional evaluation for guiding coronary intervention. A randomized clinical non-inferiority trial

Evaluation of coronary artery stenosis requires objective evidence of its
ischemic potential. Current official guidelines indicate assessment of the
physiological significance of a coronary stenosis by fractional flow reserve
(FFR) (class 1A indication by European Society of Cardiology official
guidelines on myocardial revascularization (1)). FFR is the reduction in flow
induced by a stenosis and a pressure drop exceeding 20% (FFR<= 0.80) indicates
that a stenosis may cause ischemia in the supplied territory. FFR is assessed
as the pressure drop across a stenosis during medically induced hyperaemia. The
pressure distal to the stenosis is measured by a pressure transducer on a thin
wire. The need for using a pressure wire limits this approach due to potential
difficulties advancing the wire, risk of dissections, and the associated costs.
Quantitative flow ratio (QFR) is a novel diagnostic tool to compute FFR based
on angiographic images. QFR allows for *wire free* FFR assessment as it does
not require a pressure transducer to be placed in the coronary artery. Medical
induced hyperaemia is required for standard FFR and causes patient discomfort
and, in rare cases, arrhythmia and impaired breathing. With QFR, hyperaemia is
modelled by the application and medical induction is not needed.
QFR is based on a combination of coronary anatomy assessed by X-ray angiography
and estimated flow velocity in the vessel based on modified frame count
analysis.
The FAVOR II study demonstrated that QFR is feasible in clinical practice and
lesions are classified comparable to FFR with diagnostic precision of 88%-92%
(FAVOR II Europe-Japan and FAVOR II China) for intermediate lesions. QFR has
the potential to reduce procedural costs substantially compared to the pressure
wire-based FFR strategy, but it is unknown if QFR assessment results in
clinical outcome comparable to that of the pressure wire based approach.
To demonstrate the clinical value of a QFR based diagnostic approach a
randomized, adequately powered, non-inferiority trial is required; the FAVOR
III trial.

To investigate if a QFR-based diagnostic strategy yields non-inferior 12-month
clinical outcome compared to a standard pressure-wire guided strategy in
evaluation of patients with stable angina pectoris and intermediate coronary
stenosis.

Investigator initiated, 1:1 randomized, prospective, clinical outcome,
non-inferiority, multi-center trial performed at up to 40 international sites.

randomization (1:1) to QFR based evaluation of FFR based evaluation of
intermediate coronary stenosis.

For patients randomized to the QFR based strategy, obtaining 1-2 extra
angiographic recordings per vessel interrogated might be necessary. The
potential extra amount of contrast is estimated to be up to 15mL and the
radiation exposure can increase by up to 0.1 mSv per analyzed vessel, equaling
up to 0.3 mSv increase in total for each patient. The radiation dose for a
standard diagnostic coronary angiography is 1-2 mSv. This limited additional
contrast load and radiation exposure is not supposed to cause any measurable
increased risk for the patient. A total dose of 2 mSv is associated with an
increased risk of 0.01% for developing incurable cancer. Interventional
cardiologists and support staff at the participating sites are well trained to
manage and reduce any procedural risks.