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<middle dot>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 QFRguided strategy (1008 patients) or the FFR-guided strategy (992 patients). The median age was 67<middle dot>3 years (IQR 59<middle dot>9-74<middle dot>7); 1538 (76<middle dot>9%) patients were male and 462 (23<middle dot>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<middle dot>7%) patients in the QFR group, and in 41 (4<middle dot>2%) patients in the FFR group (hazard ratio 1<middle dot>63 [95% CI 1<middle dot>11-2<middle dot>41]). The event proportion difference was 2<middle dot>5% (90% two-sided CI 0<middle dot>9-4<middle dot>2). The upper limit of the 90% CI exceeded the prespecified non-inferiority margin of 3<middle dot>4%. Therefore, QFR did not meet non-inferiority to FFR. A total of 18 (1<middle dot>8%) patients in each group experienced an adverse procedural event, the most frequent being procedure-related myocardial infarction, which occurred in ten (1<middle dot>0%) patients in the QFR group and seven (0<middle dot>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. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.