FAVOR III Europe (Functional Diagnostic Accuracy of Quantitative Flow Ratio in Online Assessment of Coronary Stenosis III Europe) was a multicenter, randomized, open-label, noninferiority trial to compare clinical outcomes of quantitative flow ratio (QFR)-guided and fractional flow reserve (FFR)-guided revascularization in patients with intermediate coronary stenosis (40-90% diameter stenosis by visual estimation) at 12 months.¹

The study was conducted in 34 centers across 11 European countries. It enrolled 2,000 adult patients with an indication for invasive coronary angiography due to stable angina, acute non–ST-segment elevation myocardial infarction (NSTEMI), or staged evaluation following NSTEMI or STEMI >24 hours prior, with at least one intermediate nonculprit lesion. Patients were randomized 1:1 to either revascularization with a QFR-guided strategy (1,008 patients) or an FFR-guided strategy (992 patients). The primary endpoint was the rate of major adverse cardiovascular events (MACE); a composite of all-cause death, myocardial infarction, and unplanned revascularization assessed at 12 months.

At 12 months, the primary endpoint 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% confidence interval [CI], 1.11-2.41). The event proportion difference was 2.5% (90% two-sided CI, 0.9-4.2). Given that the upper limit of the CI exceeded the prespecified noninferiority margin (3.4%), the results of this study do not support using QFR if FFR is available. Moreover, the total number of stents implanted was higher in the QFR-guided strategy (n=823) when compared to the FFR-guided strategy (n=650). Interestingly, compared to FFR, QFR showed more functionally significant lesions in the left circumflex system (37.1% vs. 15.4).

Limitations of this trial included lack of blinding, male predominance, and absence of race/ethnicity diversity, which limit generalizability.

Unlike FAVOR III China,² which assessed QFR to angiography alone, FAVOR III Europe was unable to show noninferiority of QFR to FFR in revascularization of intermediate coronary stenoses. Additional research is needed to assess the feasibility of QFR to improve clinical outcomes in intermediate coronary stenoses.

References

1. Andersen BK, Sejr-Hansen M, Maillard L, et al. Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial [published correction appears in Lancet. 2025 Dec 21;404(10471):2542. doi: 10.1016/S0140-6736(24)02753-3. Lancet. 2024;404(10465):1835-1846. doi:10.1016/S0140-6736(24)02175-5.
2. Xu B, Tu S, Song L, et al. Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial. Lancet. 2021;398(10317):2149-2159. doi:10.1016/S0140-6736(21)02248-0.