Key Points
• In the FAST III trial, a vFFR guided revascularization strategy was noninferior to an FFR guided strategy for the 1-year composite of death, myocardial infarction, or any revascularization in patients with intermediate coronary lesions.
• The primary endpoint occurred in 7.5% of patients in both groups in the full analysis set, with a risk difference of minus 0.02% and P for noninferiority = 0.004.
• vFFR guidance was associated with a somewhat shorter procedure time but a higher rate of revascularization of at least one study lesion compared with FFR guidance.
Current guidelines recommend physiological assessment of intermediate coronary lesions to guide revascularization. Data regarding revascularization guided by vessel fractional flow reserve (vFFR), derived from three-dimensional quantitative coronary angiography without the need for a pressure wire or hyperemic agent, as compared with pressure-wire–based fractional flow reserve (FFR), are lacking. The FAST III trial [NCT04931771] compared angiography derived vessel fractional flow reserve with conventional pressure wire based fractional flow reserve for revascularization guidance. The trials results were presented at ACC 2026 with simultaneous publication in New England Journal of Medicine. The objective of FAST III is to determine the safety and effectiveness of an angiography-based vessel-Fractional Flow Reserve guided strategy versus an invasive FFR guided strategy to guide coronary revascularization in patients with intermediate coronary artery stenosis.
FAST III was designed as a randomized comparison of vFFR guided versus FFR guided revascularization in adults with at least one intermediate native coronary lesion with 30% to 80% diameter stenosis suitable for physiological assessment. A total of 2,235 patients were randomized across 37 sites in 7 countries between November 2021 and May 2024. In the full analysis set, 1,116 patients were included in the vFFR arm and 1,095 patients in the FFR arm.
Baseline characteristics were well balanced between groups. The mean age was approximately 67 years, about one quarter of participants were women, and the majority underwent angiography for chronic coronary syndrome, while smaller proportions presented with unstable angina or NSTEMI. Diabetes was present in roughly one quarter of patients, and prior PCI in about one third. The primary endpoint was a composite of all cause death, any myocardial infarction, or any revascularization within 1 year after randomization. In the full analysis set, this occurred in 80 of 1,116 patients in the vFFR group and 79 of 1,095 patients in the FFR group, corresponding to 7.5% in both arms. The risk difference was minus 0.02%, with a 95% confidence interval of minus 2.25% to 2.21%, meeting the criterion for noninferiority (P for noninferiority = 0.004).
The per protocol analysis was directionally consistent. The primary endpoint occurred in 7.0% of the vFFR group and 7.4% of the FFR group, with a risk difference of minus 0.40% and a confidence interval ranging from minus 2.65% to 1.86%. Key secondary outcomes were also similar between groups. Study vessel failure, defined as the composite of cardiac death, study vessel myocardial infarction, or clinically indicated study vessel revascularization, occurred in 4.0% of the vFFR arm and 4.6% of the FFR arm, for a risk difference of minus 0.62%. Rates of death from any cause, cardiac death, any myocardial infarction, any revascularization, clinically indicated revascularization, stroke, and definite or probable stent thrombosis were low and broadly comparable between strategies. From a procedural standpoint, complete physiological assessment was achieved in 96.7% of the vFFR group and 99.1% of the FFR group. Revascularization of at least one study lesion occurred more often with vFFR guidance, 45.0% versus 36.0%, although adherence to physiology-based decision making was high in both groups, at approximately 96%. Mean procedure time among patients undergoing PCI was modestly shorter with vFFR guidance, 55.8 minutes versus 60.9 minutes with FFR.
Overall, FAST III showed that among patients with intermediate coronary artery lesions, a vFFR guided revascularization strategy was noninferior to an FFR guided strategy with respect to the composite of death, myocardial infarction, or revascularization at 1 year. These findings support the use of angiography-based physiology as a practical alternative to pressure wire-based assessment in appropriately selected patients.