Results from a landmark international trial recently published in the New England Journal of Medicine found that a software-based tool that uses artificial intelligence to calculate fractional flow reserve (FFR) in patients with coronary artery disease was both clinically similar to and saved time over conventional FFR, the current standard, which is a more invasive, pressure wire-based procedure.
The Advancing Cath Lab Results with FFRangio Coronary Physiology Assessment (ALL-RISE) trial was a randomized, multicenter trial in 59 sites across the U.S., Japan, Israel, Switzerland, and the United Kingdom, and compared clinical outcomes between traditional FFR and the novel method. FFRangio uses advanced computations guided by AI to create a 3D model of a patient’s arteries using angiogram images, providing a physiological assessment of lesions affecting blood flow and contributing to stenosis, and helping physicians determine if percutaneous coronary intervention may be needed.
“One of our goals was to help clinicians increase adoption of physiologic testing, which is class 1A in guidelines, by making it as simple as having a routine angiogram,” explains Ajay Kirtane, M.D., interventional cardiologist at NewYork-Presbyterian, director of Columbia Interventional Cardiovascular Care, and senior author of the study, who presented the trial results at the American College of Cardiology’s 2026 Annual Scientific Session.
Although previous research has shown physiologic assessment improves patient outcomes — and likely reduces unnecessary stent procedures — adoption has been low, in part due to the added steps and time required to place a pressure wire and measure coronary flow.
“To date, there haven’t been positive trials for angiography-based physiology compared with traditional wire-based assessment,” he adds. “Now that we’ve demonstrated similar one-year results in the cath lab in conjunction with a streamlined workflow, we’re hoping this testing is done more frequently to help more patients get optimal care.”
We demonstrated not only clinical noninferiority, but also tangible workflow benefits that will hopefully contribute to physiology adoption as a whole.
— Dr. Ajay Kirtane
ALL-RISE Trial Results
More than 1,900 adults were enrolled in the trial and were randomly assigned to receive treatment based upon either FFRangio or wire-based physiology. The main inclusion criteria was having at least one coronary stenosis of 50%-90%, and the primary endpoint was a major adverse cardiovascular event (defined as all-cause death, myocardial infarction, or unplanned, clinically indicated coronary revascularization) at one year, with the noninferiority margin at 3.5 percentage points.
The findings revealed that 6.9% of patients in the FFRangio group experienced a primary endpoint, compared with 7.1% in the conventional FFR group. There were also no major differences in procedure-related adverse events.
In addition, FFRangio demonstrated several operational efficiencies and patient benefits: It was faster to perform; did not require additional catheters, wires, or the administration of medication, as is typical with pressure wire-based procedures; required a lower volume of contrast media; and reduced patient radiation exposure. There were also seven bleeding events in the FFRangio arm and 14 in the wire-based arm, perhaps due to the need to administer blood thinners when performing wire-based physiology.
“Some people feel that the wire may be faster, but it turns out that we saved time with FFRangio. In fact, overall procedure times were quicker,” says Dr. Kirtane. “So, we demonstrated not only clinical noninferiority, but also tangible workflow benefits that will hopefully contribute to physiology adoption as a whole.”
Expanding Future Use of FFRangio
Looking ahead, Dr. Kirtane and the other investigators have plans to further assess the trial results to determine the cost savings of using FFRangio over traditional FFR. He also believes the technology could be used to gather information on other patient populations, such as non-ST-segment elevation myocardial infarction (NSTEMI) patients or those with concomitant valvular disease.
“What’s nice about an angiography-based paradigm is that it doesn’t require invasive manipulation,” says Dr. Kirtane. “This opens the door to a host of other use cases that could give patients and clinicians the information they need to guide their decision-making.”
