FFR Angiography Noninferior to Pressure-Wire Strategy in CAD Analysis, With William Fearon, MD

Angiography-guided fractional flow reserve (FFR) is noninferior to a pressure-wire-guided strategy in patients with coronary artery disease (CAD), according to data from the ALL-RISE study.1,2

These data were presented at the American College of Cardiology (ACC) Scientific Sessions 2026 in New Orleans, Louisiana, by William Fearon, MD, professor of medicine and director of interventional cardiology at Stanford University School of Medicine, and Ajay Kirtane, MD, director of Columbia Interventional Cardiovascular Care and professor of medicine at Columbia University Irving Medical Center.

Guidelines have long endorsed the invasive measurement of FFR or non-hyperemic pressure ratios (NHPRs) to improve clinical outcomes among patients with CAD. Despite this, the use of wire-based physiology is still low. The computation of physiologic indices derived from coronary angiography (FFRangio), however, does not require systemic anticoagulation, a pharmacologic hyperemic agent, a guiding catheter, or a coronary pressure wire.1

“The key difference is that every time we bring a patient to the cath lab, we have to do an angiogram in order to see what’s going on,” Fearon told HCPLive in an exclusive interview. “Since you’re already doing that, the FFRangio is basically just using that information to calculate the FFR, and it takes an extra six minutes – I think that could be even quicker as people get more familiar with the system. But either way, that was significantly less time than it took to do a pressure wire measurement in the study.”

The Advancing Cath Lab Results with FFRangio Coronary Physiology Assessment (ALL-RISE) trial, a multicenter, international, randomized non-inferiority clinical outcome study, aimed to prove the FFRangio’s noninferiority to the pressure-wire-guided strategy. Patients were eligible if they had ≥1 intermediate coronary stenosis – those who were included were randomized to FFRangio via the CathWorks system or to wire-based FFR/NHPR assessment. After assessment, they were treated with medical therapy or percutaneous coronary intervention as indicated by the measurements.1

The study’s primary outcome was a composite of death, myocardial infarction, or unplanned, clinically-indicated coronary revascularization at 1 year. Key secondary outcomes included procedural time, contrast media utilization, and fluoroscopy time.1

A total of 4704 patients were screened for eligibility; 1930 were randomized, with 965 assigned to each arm. Mean participant age was 68.4 +/- 10.2 years, and the majority (90.6%) presented without elevated cardiac biomarkers. At baseline, most patients had a single lesion for assessment, and the left anterior descending artery contained this lesion in 49.6% of patients.2

FFRangio assessment was successful in 98.5% of lesions, with a mean value of 0.81 +/- 0.12. 43% of measurements had an abnormal value, defined as ≤0.8. Pressure-wire-based physiological measurements were successful in 98.6% of lesions – of those, 55.5% were assessed with FFR and 44.5% with NHPR. Mean FFR value was 0.84 +/- 0.1, while the mean NHPR value was 0.89 +/- 0.11. Additionally, 37% of the lesions measured with pressure wire had an abnormal value.2

The median time to calculate the assessment was 6 minutes in the FFRangio group and 8 minutes in the pressure-wire group, with a between-group difference of -2 minutes (95% CI, -3 to -2). PCI was performed in 44.3% of lesions assessed with FFRangio and 35.4% with a pressure wire (OR, 1.45; 95% CI, 1.24 to 1.7). By 1 year, a primary endpoint event occurred in 64 patients in the FFRangio group and 65 patients in the pressure-wire group (HR, 0.98; 95% CI, 0.7 to 1.39; P <.001 for noninferiority) with a difference of -0.2 percentage points. Additionally, investigators recorded no differences between groups for the incidence of bleeding, acute kidney injury, or procedure-related adverse events.2

“This was a very positive study,” Fearon said. “I think that, given the benefits of shorter time, less contrast, and less radiation, there’s really no reason not to incorporate this into your daily practice.”

Editors’ Note: Fearon reports disclosures with Abbott Vascular, CathWorks, Medtronic, Heartflow, Edwards Lifesciences, Shockwave, and others.

References

1. Fearon W, Jeremias A, Leon B, et al. A Large-scale, Global Randomized Trial of Coronary Physiology Derived from Conventional Angiography Compared With an Invasive Pressure Wire-based Approach to Guide Percutaneous Coronary Intervention. Abstract presented at the American College of Cardiology Scientific Sessions 2026 in New Orleans, LA. March 28-30, 2026.

2. Fearon WF, Jeremias A, Witberg G, et al. Angiography-derived Fractional Flow Reserve to guide PCI. New England Journal of Medicine. Published online March 29, 2026. doi:10.1056/nejmoa2600949