Andersen BK, Sejr-Hansen M, Maillard L, Campo G, Råmunddal T, Stähli BE, Guiducci V, Serafino LD, Escaned J, Santos IA, López-Palop R, Landmesser U, Dieu RS, Mejía-Rentería H, Koltowski L, Žiubrytė G, Cetran L, Adjedj J, Abdelwahed YS, Liu T, Mogensen LJH, Eftekhari A, Westra J, Lenk K, Casella G, Belle EV, Biscaglia S, Olsen NT, Knaapen P, Kochman J, Santos RC, Scarsini R, Christiansen EH, and Holm NR
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., Competing Interests: Declaration of interests BKA reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. GCam reports institutional research grants from SMT, Medis Medical Imaging, Abbott Vascular, GADA, Siemens, and GE Healthcare outside the present work. TR reports consultant and proctoring honoraria from Boston Scientific, EPS Vascular, and Cardirad. BES is supported by the H H Sheikh Khalifa bin Hamad Al-Thani Research Programme; has received research grants to the institution from Boston Scientific, the B Braun Foundation, the German Center for Cardiovascular Research (DZHK), the German Heart Research Foundation, Edwards Lifesciences, the Iten-Kohaut Foundation, and the OPO Foundation; has received consulting and speaker fees from Abbott Vascular, Abiomed, and Boston Scientific; and received free licences for the QFR application from Medis Medical Imaging during the trial. LDS reports consulting fees from Abbott Vascular, Boston Scientific, and Philips outside the submitted work. JE reports serving as a speaker or advisory board member for Abbott, Boston Scientific, Medis Medical Imaging, and Philips. RL-P received a free licence for the QFR software from Medis Medical Imaging during the trial. UL reports research grants to the institution from Abbott, Amgen, Bayer, and Novartis. RSD reports an institutional research grant from Medis Medical Imaging and free licences for the QFR application from Medis Medical Imaging during the trial. HM-R reports consultancy fees from Medis Medical Imaging and speaker fees from Philips and Abbott. LK received free licences for the QFR application from Medis Medical Imaging during the trial. JA reports teaching grants from Biotronik and Medis Medical Imaging. YSA reports consulting fees from Boston Scientific and Shockwave. TL served as a Medis technical and research support consultant in Haga Hospital (The Hague, Netherlands) and performed beta testing of software from Medis Medical Imaging, neither of which was study related, and received a free licence for the QFR application from Medis Medical Imaging during the trial. KL received free licences for the QFR application from Medis Medical Imaging during the trial; speaker fees and travel support from BMS and Boston Scientific; speaker fees from DGK; and served as an advisory board member for BMS. GCas received a free licence for the QFR application from Medis Medical Imaging during the trial. SB reports institutional research grants from Medis Medical Imaging, SMT, Abbott, Siemens, Insight Lifetech, and Amgen; free licences for the QFR application from Medis Medical Imaging during the trial; speaker's fee from SMT, Medis Medical Imaging, Abbott, and Siemens; and advisory board activities for Siemens. NTO reports institutional research grants from Abbott and from Shockwave. RS reports an institutional research grant from Abbott; institutional research contract with Medis Medical Imaging; and speaker and consultation fees from Abbott and Fondazione Menarini. EHC reports institutional research grants from Abbott, Biosensors, Meril, and Medis Medical Imaging; and speaker fees from Abbott and EPS. NRH reports Institutional research grants from Abbott, B Braun, Biosensors, Boston Scientific, and Medis Medical Imaging; and speaker fees from Abbott and EPS. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)