Angiography-Based Physiology to Guide Coronary Revascularization
Key result
vFFR-guided revascularization matches standard FFR for 1-year major cardiovascular events.
- risk difference -0.02 percentage points
- 95% CI -2.25 to 2.21
- P=0.004 for noninferiority
- n=2,211
Why the trial?
The FAST III trial was conducted to address the lack of data comparing vessel fractional flow reserve (vFFR), derived from 3D quantitative coronary angiography without pressure wire or hyperemic agent, to the standard pressure-wire-based fractional flow reserve (FFR) for guiding revascularization in patients with intermediate coronary lesions.
Does vFFR-guided revascularization provide noninferior clinical outcomes compared to FFR-guided revascularization in patients with intermediate coronary-artery lesions?
Key Points
- To determine whether coronary revascularization guided by angiography-derived vessel fractional flow reserve (vFFR) is noninferior to standard pressure-wire-based fractional flow reserve (FFR) in patients with intermediate coronary lesions.
- International, open-label, randomized noninferiority trial conducted at 37 European sites (NCT04931771).
- A total of 2,211 patients with intermediate coronary stenosis (30% to 80%) were randomly assigned 1:1 to either vFFR-guided (N=1116) or FFR-guided (N=1095) revascularization.
- The primary end point was a 1-year composite of death from any cause, myocardial infarction, or revascularization, assessed against a noninferiority margin of 3.0 percentage points.
- At 1 year, the primary composite end point occurred in 7.5% of patients (80/1116) in the vFFR group compared to 7.5% of patients (79/1095) in the FFR group (risk difference, -0.02 percentage points; 95% CI, -2.25 to 2.21; P=0.004 for noninferiority).
- Serious adverse event rates were similar between the two treatment strategies.
Study Design
Type
RCT (n=2,211)
Blinding
open-label
Randomization
1:1 ratio
Multicenter
Yes
Structured PICO
Does vFFR-guided revascularization provide noninferior clinical outcomes compared to FFR-guided revascularization in patients with intermediate coronary-artery lesions?
P
Population
2,211 patients with intermediate coronary-artery lesions presenting with chronic or acute coronary syndromes, followed for 1 year.
I
Intervention
vFFR-guided revascularization (vessel fractional flow reserve derived from three-dimensional quantitative coronary angiography without pressure wire or hyperemic agent)
C
Comparator
FFR-guided revascularization (pressure-wire-based fractional flow reserve)
O
Outcome
Composite of death from any cause, any myocardial infarction, or any revascularization at 1 yearcomposite
Main Result
Absolute Risk Reduction: -0.02 (95% CI -2.25–2.21)
Absolute Event Rate: 7.5% vs 7.5%
Absolute Risk Reduction: -0.02%
p-value: p=0.004 for noninferiority
Angiography-derived vFFR is noninferior to pressure-wire-based FFR for guiding revascularization in intermediate coronary lesions, offering a wire-free alternative for physiological assessment.
Discussion
Key questions
No takes yet. Share an insight, caveat, or question.
Where experts stand
Experts read FAST III as a meaningful step toward replacing pressure wires with angiography-based physiology, though the reaction comes largely from investigators and industry partners rather than independent voices.
The trial's noninferiority finding has been welcomed as confirmation that angiography-based vFFR can safely guide revascularization while simplifying procedures. Commentators highlight the potential to expand physiology-guided decision-making to patients who currently get treated based on visual assessment alone. The open question is whether independent practitioners and guideline bodies will adopt vFFR broadly or await longer follow-up and real-world validation.
Agreement
Both credentialed clinicians agree that FAST III supports vFFR as a safe, less-invasive alternative to pressure wire-based FFR that could broaden the use of physiology-guided revascularization for intermediate coronary lesions.
2 clinicians say this directly
Still unclear
Whether the noninferiority finding will translate into guideline endorsement of angiography-based physiology as a first-line strategy remains to be seen. Experts have not addressed how vFFR performs in more complex anatomy or whether longer follow-up could reveal differences between approaches.
Key expert perspectives
Yiannis S. ChatzizisisDirector, Center for Digital Cardiovascular Innovations, University of MiamiPractice takeMar 31An important step toward a new standard of care, not yet definitively practice-changing
Chatzizisis frames FAST III as meaningful support for a less-invasive physiology-guided strategy in an era dominated by artificial intelligence. He sees it as potentially simplifying decision-making for the majority of patients with stable or unstable intermediate coronary lesions, while stopping short of calling it fully practice-changing on its own.
Distilled from their postOriginal post
JDJoost DaemenInterventional cardiologist, Erasmus University Medical CenterPractice takeMar 31
vFFR could boost physiology use in patients still managed by eye-balling
Daemen says the results confirm the safety and feasibility of online vFFR as a minimally invasive tool for guiding revascularization of intermediate lesions. He argues the technology could increase physiology adoption in patients whose treatment decisions still rely on visual assessment, eliminating the need for guiding catheters, coronary instrumentation, and hyperemic agents.
Implication
Opens wire-free physiology assessment for intermediate lesions; extends randomized evidence beyond wire-based FFR.
Abstract
BACKGROUND: Current society 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. METHODS: We conducted an international, open-label, randomized, noninferiority trial at 37 sites in Europe. Patients with intermediate coronary-artery lesions (diameter stenosis of 30 to 80%) who presented with chronic or acute coronary syndromes were randomly assigned in a 1:1 ratio to undergo either vFFR-guided or FFR-guided revascularization of the intermediate coronary-artery lesions. The primary end point was a composite of death from any cause, any myocardial infarction, or any revascularization at 1 year. The noninferiority margin was 3.0 percentage points. RESULTS: The primary end point was assessed in 1116 patients in the vFFR group and 1095 in the FFR group. The mean age of the patients was 67 years, 24.3% were women, 18.7% presented with an acute coronary syndrome, and 26.6% had diabetes mellitus. At 1 year, a primary end-point event had occurred in 80 patients (Kaplan-Meier estimate, 7.5%) in the vFFR group and in 79 patients (Kaplan-Meier estimate, 7.5%) in the FFR group (risk difference, -0.02 percentage points; 95% confidence interval, -2.25 to 2.21; P = 0.004 for noninferiority). The incidence of serious adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with intermediate coronary lesions, vFFR-guided revascularization was noninferior to FFR-guided revascularization with respect to a composite of death, myocardial infarction, or revascularization at 1 year. (Funded by Pie Medical Imaging and Siemens Healthineers; FAST III ClinicalTrials.gov number, NCT04931771.).
Coverage & sources
Journal, society, and media accounts. Useful signal, not independent expert judgment.
Cite This Study
Daemen et al. (2026) conducted an RCT in intermediate coronary-artery lesions (n=2,211). vFFR-guided revascularization vs. FFR-guided revascularization was evaluated on composite of death from any cause, any myocardial infarction, or any revascularization at 1 year (risk difference -0.02 percentage points, 95% CI -2.25 to 2.21, p=0.004 for noninferiority). vFFR-guided revascularization was noninferior to FFR-guided revascularization for a composite of death, myocardial infarction, or revascularization at 1 year (7.5% vs 7.5%; P=0.004 for noninferiority).