Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial

Background: Fractional flow reserve (FFR) or non-hyperaemic pressure ratios are recommended to assess functional relevance of intermediate coronary stenosis. Both diagnostic methods require the placement of a pressure wire in the coronary artery during invasive coronary angiography. Quantitative flow ratio (QFR) is an angiography-based computational method for the estimation of FFR that does not require the use of pressure wires. We aimed to investigate whether a QFR-based diagnostic strategy yields a non-inferior 12-month clinical outcome compared with an FFR-based strategy.

Methods: FAVOR III Europe was a multicentre, randomised, open-label, non-inferiority trial comparing a QFR-based with an FFR-based diagnostic strategy for patients with intermediate coronary stenosis. Enrolment was performed in 34 centres across 11 European countries. Patients aged 18 years or older with either chronic coronary syndrome or stabilised acute coronary syndrome, and with at least one intermediate non-culprit stenosis (40-90% diameter stenosis by visual estimate; referred to here as a study lesion), were randomly assigned (1:1) to the QFR-guided or the FFR-guided group. Randomisation was done using a concealed web-based system and was stratified by diabetes and presence of a left anterior descending coronary artery study lesion. The primary endpoint was a composite of death, myocardial infarction, and unplanned revascularisation at 12 months. The predefined non-inferiority margin was 3·4% and the primary analysis was performed in the intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT03729739) and long-term follow-up is ongoing.

Findings: Between Nov 6, 2018, and July 21, 2023, 2000 patients were enrolled and randomly assigned to the QFR-guided strategy (1008 patients) or the FFR-guided strategy (992 patients). The median age was 67·3 years (IQR 59·9-74·7); 1538 (76·9%) patients were male and 462 (23·1%) were female. Median follow-up time was 365 days (IQR 365-365). At 12 months, a primary endpoint event had occurred in 67 (6·7%) patients in the QFR group, and in 41 (4·2%) patients in the FFR group (hazard ratio 1·63 [95% CI 1·11-2·41]). The event proportion difference was 2·5% (90% two-sided CI 0·9-4·2). The upper limit of the 90% CI exceeded the prespecified non-inferiority margin of 3·4%. Therefore, QFR did not meet non-inferiority to FFR. A total of 18 (1·8%) patients in each group experienced an adverse procedural event, the most frequent being procedure-related myocardial infarction, which occurred in ten (1·0%) patients in the QFR group and seven (0·7%) in the FFR group. One patient in the QFR group died in relation to the index procedure.

Interpretation: The results of the FAVOR III Europe trial do not support the use of QFR if FFR is available to guide revascularisation decisions in patients with intermediate coronary stenosis. This finding could have implications for current clinical guidelines recommending QFR for this purpose.

Funding: Medis Medical Imaging Systems and Aarhus University.