Coronary physiologic assessment to guide revascularization for intermediate coronary lesions in the catheterization laboratory is strongly recommended by current guidelines, yet remains underutilized in routine practice due to workflow complexity, procedural time, and the need for additional catheter manipulation with pressure wire-based approaches.¹ At the American College of Cardiology (ACC) Annual Scientific Session 2026, Dr. Ajay Kirtane from the Columbia University Irving Medical Center, United States, presented results from the ALL-RISE trial, demonstrating that angiography-derived fractional flow reserve (FFRangio) is non-inferior to conventional pressure wire-based physiology assessment in guiding percutaneous coronary intervention (PCI) for intermediate coronary lesions.¹

FFRangio is a Food and Drug Administration (FDA)-approved software-based technology that derives coronary physiologic assessment directly from routine coronary angiography without requiring pressure wire manipulation or pharmacologic hyperemia.¹ Using artificial intelligence (AI), computer vision, and computational flow algorithms, the system reconstructs a three-dimensional (3D) coronary model and calculates fractional flow reserve (FFR) values throughout the coronary tree under physician oversight.¹ Previous validation studies have demonstrated good agreement between FFRangio and conventional pressure wire-based FFR measurements, although randomized clinical outcomes data had previously been limited.¹

Against this background, the multinational, randomized, non-inferiority ALL-RISE trial was designed to evaluate whether FFRangio-guided treatment was comparable to conventional pressure wire-based assessment for intermediate coronary lesions being considered for PCI.¹ A total of 1,930 patients with chronic coronary syndrome (CCS) or non-ST-elevation acute coronary syndrome (NSTEACS) and angiographically significant 50%-90% coronary lesions were randomized 1:1 to either FFRangio-guided or pressure wire-guided assessment, with stratification according to clinical presentation and physiology strategy using either hyperemic FFR or non-hyperemic pressure ratio (NHPR).¹ The primary endpoint was 1-year major adverse cardiovascular events (MACE), defined as all-cause death, myocardial infarction (MI), or unplanned clinically driven revascularization.¹

Baseline characteristics were well balanced between groups, with a mean age of 68 years and approximately 40% of patients having diabetes.¹ Among lesions declared as study lesions, approximately 50% were located in the left anterior descending (LAD) artery.¹ Physiologic assessment was successful in >98% of lesions in both treatment arms.¹ Mean FFRangio values were 0.81, while conventional pressure wire-based FFR and NHPR values were 0.84 and 0.89, respectively, indicating that most interrogated lesions were close to standard treatment thresholds.¹ PCI was ultimately performed in 44.3% of patients in the FFRangio arm and 35.4% in the pressure wire arm.¹

The study met its primary endpoint for non-inferiority, with the upper bound of the confidence interval (CI) for the difference in event rates at 2.1%, well below the prespecified non-inferiority margin of 3.5%.¹ At 1 year, MACE occurred in 6.9% of patients undergoing FFRangio-guided treatment vs. 7.1% in the pressure wire-guided group (Hazard ratio [HR]=0.98; 95% CI: 0.70-1.39; p for non-inferiority=0.0008).¹ Rates of death, MI, and unplanned clinically driven revascularization were also comparable between groups, with death occurring in 2.3% vs. 2.1% of patients (HR=1.16; 95% CI: 0.63-2.14), MI in 1.6% vs. 2.5% (HR=0.65; 95% CI: 0.34-1.25), and unplanned clinically driven revascularization in 4.1% vs. 4.6% (HR=0.90; 95% CI: 0.58-1.40) in the FFRangio and pressure wire groups, respectively.¹

Subgroup analyses similarly demonstrated generally consistent findings across prespecified populations, with nominal interactions in LAD lesions and FFR strata that should be interpreted cautiously, as the study was not powered for subgroup analysis.¹ One-year secondary endpoints likewise showed broadly comparable efficacy and safety outcomes between groups across measures, with a numerically lower rate of bleeding observed in the FFRangio group vs. the pressure wire group, although overall bleeding rates remained low.¹

In addition to comparable clinical outcomes, FFRangio improved procedural efficiency.¹ FFRangio-derived physiology required no additional procedural manipulation beyond routine angiography, with median physiology assessment time reduced from 8 to 6 minutes vs. pressure wire assessment.¹ Total fluoroscopy time, contrast volume, and overall procedure duration were also lower with FFRangio-guided assessment, despite a slightly higher rate of PCI.¹ Overall procedure time was shortened by a median of 5 minutes per case.¹

In conclusion, the ALL-RISE trial demonstrated that angiography-derived FFR provides clinical outcomes non-inferior to conventional pressure wire-based physiology assessment while offering a simplified and more efficient workflow in the catheterization laboratory.¹ These findings support the routine integration of FFRangio into PCI decision-making for intermediate coronary lesions and may help expand adoption of guideline-recommended coronary physiologic assessment in routine clinical practice.¹