By Jeffrey Zimmet, MD, PhD
Synopsis: In this large, multicenter, randomized trial, use of the angiography-based quantitative flow ratio method to guide revascularization of intermediate coronary stenoses resulted in a higher incidence of major adverse cardiac events at one year compared with pressure wire-based fractional flow reserve.
Source: 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. Lancet. 2024;404(10465):1835-1846. [Erratum in: Lancet. 2025;404(10471):2542.]
Compared with the use of visual estimates of percent stenosis, physiology-based techniques including fractional flow reserve (FFR) lead to a reduction in the need for coronary intervention and improved outcomes. International guidelines, therefore, recommend FFR to guide treatment of intermediate coronary stenoses. FFR and other pressure wire methods, such as instantaneous wave-free ratio (iFR), are more invasive than angiography alone, requiring full anticoagulation and wiring the vessel, which adds time, cost, and some additional risk of procedural complications.
In recent years, several computational methods have been developed that analyze the coronary angiogram itself and come up with a quantitative analysis of the lesions. One of these methods, known as quantitative flow ratio, or QFR (Medis Medical Imaging), has received a Class I recommendation in the 2024 European Society of Cardiology (ESC) guidelines for the management of intermediate coronary stenoses in chronic coronary syndromes. The previously published FAVOR III China trial had shown QFR to be superior to routine angiographic guidance in guiding treatment decisions.
FAVOR III Europe was designed to test QFR against the FFR gold standard, looking not at concordance of result but rather at clinical outcomes. To this end, 2,000 patients were enrolled at 34 centers in 11 European countries. After stratification by diabetes status and presence or absence of disease in the left anterior descending artery, subjects were randomly assigned to either an FFR- or QFR-based treatment strategy.
The median age was 66 years, and 23% were female. Two-thirds of patients presented with chronic coronary disease, and one-quarter for non-culprit evaluation after initial interventional procedures for acute coronary syndromes. Eight percent of subjects had non-ST-elevation myocardial infarction (NSTEMI) at the time of randomization.
For both FFR and QFR, a value of ≤ 0.80 was used as the cutoff for proceeding to revascularization. The average QFR value was 0.84, compared with an average of 0.81 for FFR. In the QFR group, 46.2% of lesions were identified as significant compared with 38.2% of lesions in the FFR group. This resulted in 27% higher stent use in the QFR group: 823 in the QFR group and 650 in the FFR group. Lesions in the circumflex distribution specifically were more than twice as likely to be functionally significant by QFR compared with FFR.
Total procedure time and contrast volume were similar between the two groups, although fluoroscopy time was greater in the FFR group. Procedural complications were low and were not significantly different between groups.
The primary outcome, a composite of all-cause death, myocardial infarction, and unplanned revascularization at 12 months, occurred in 6.7% of patients assigned to QFR guidance vs. 4.2% assigned to FFR. The hazard ratio (HR) was 1.63 (95% confidence interval [CI], 1.11-2.41; two-sided P = 0.013). This 2.5% difference did not meet the prespecified noninferiority margin of 3.4%. The observed difference in major adverse cardiac events was driven primarily by myocardial infarction, which occurred in 3.7% of the QFR group and in 2.0% of the FFR group (HR, 1.84; 95% CI ,1.07-3.17; P = 0.028). Interestingly, although the QFR group underwent significantly more intervention during the index procedures, subsequent unplanned revascularization trended higher for these patients.
The authors concluded that for evaluation of intermediate coronary stenoses, a QFR-based strategy did not meet noninferiority compared with FFR guidance, based on clinical outcomes at one year. They further stated that their results do not support the use of QFR in its current form if FFR is available.
Commentary
FAVOR III Europe is a superb example of why randomized trials testing the effects of interventions on clinically important outcomes are needed. Angiography-based calculation platforms such as QFR have an obvious appeal compared with wire-based techniques. Unlike pressure wire-based methods, they avoid the need to fully anticoagulate the patient and to place a guide catheter. In some instances, such as extremely tortuous vessels, they have the potential to not only be safer but to be more accurate. It is no surprise, then, that adoption of these techniques in clinical practice has proceeded despite the absence of randomized controlled trials such as this one.
This particular trial was highly anticipated, and yet the result was unexpected. For the most part, QFR and similar systems have racked up a series of big wins in clinical trials, most of which have looked at how often the numerical results are concordant with wire-based methods. This particular trial was funded by the manufacturer of QFR, Medis Medical. The result suggests strongly that QFR should not be the method of choice in environments where FFR or iFR is available.
QFR still may hold an advantage over angiography-only assessment based on the results of the previously published FAVOR III China trial, especially in patients with markedly positive QFR testing. However, outside of diagnostic-only cardiac catheterization laboratories where FFR/iFR are not available, it is difficult to see where QFR in its current iteration will find its niche. As these technologies improve, we are likely to see results catch up with the promise. Ongoing trials, including ALL-RISE, FAST III, and PIONEER-IV, are expected to provide further information going forward.
Jeffrey Zimmet is Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center.
In this large, multicenter, randomized trial, use of the angiography-based quantitative flow ratio method to guide revascularization of intermediate coronary stenoses resulted in a higher incidence of major adverse cardiac events at one year compared with pressure wire-based fractional flow reserve.
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