The ALL-RISE (Advancing Cath Lab Results with FFRangio Coronary Physiology Assessment) trial results demonstrated that, among patients with intermediate coronary stenoses undergoing invasive angiography, an angiography-derived fractional flow reserve (FFRangio [Medtronic]) strategy was noninferior to pressure wire–based physiological assessment for death, myocardial infarction, or unplanned clinically indicated revascularization at 1 year.¹ The findings support FFRangio as a wire-free alternative for guiding revascularization while reducing procedural burden.

The investigators enrolled 1,930 patients from 59 sites across North America, Europe, Asia, and the Middle East and randomly assigned them 1:1 to FFRangio or pressure wire assessment, which permitted either fractional flow reserve (FFR) or a nonhyperemic pressure ratio. The primary endpoint occurred in 6.9% of patients in the FFR arm and in 7.1% of those in the nonhyperemic pressure ratio arm (hazard ratio, 0.98; 95% confidence interval, 0.7-1.39; p_{noninferiority} < 0.001). FFRangio was associated with shorter procedure duration (median of 39 vs. 42 min), less fluoroscopy time (9 vs. 12 min), and lower contrast volume (100 vs. 105 mL) compared with pressure wire assessment. However, FFRangio classified more lesions as physiologically significant and led to more percutaneous coronary intervention (44.3% vs. 35.4% of lesions).¹

The ALL-RISE trial results were published simultaneously with the those of the FAST III (Fractional Flow Reserve or 3D-Quantitative-Coronary-Angiography-Based Vessel-FFR-Guided Revascularization) trial, which similarly showed noninferiority of vessel FFR versus pressure wire FFR; however, the FAST III trial used FFR alone as the comparator, whereas the ALL-RISE trial included nonhyperemic pressure ratios.² These concordant findings contrast with the mixed evidence for quantitative flow ratio (QFR [Medis Medical Imaging Systems B.V.]), a similar angiography-derived physiological approach from a different vendor: the FAVOR III China (Angiographic Quantitative Flow Ratio-Guided Coronary Intervention) trial results demonstrated superiority over angiography-guided care, whereas the FAVOR III Europe (Functional Diagnostic Accuracy of Quantitative Flow Ratio in Online Assessment of Coronary Stenosis III Europe) trial results failed to establish noninferiority versus FFR.^3,4 Limitations of the ALL-RISE trial included its open-label design, 1-year follow-up, sponsor involvement in site selection and monitoring, and exclusion of higher-risk anatomy and severe ventricular dysfunction. The higher revascularization rate also raises concern for lesion-level discordance and potential overtreatment despite similar short-term outcomes.

Looking ahead, artificial intelligence may further enhance angiography-derived physiological assessment through automated vessel segmentation, lesion characterization, and prediction of physiological indexes directly from invasive coronary angiography, potentially improving workflow in the catheterization laboratory.⁵ However, these approaches will require prospective validation and demonstration of clinical benefit before widespread adoption.

References

1. Fearon WF, Jeremias A, Witberg G, et al. Angiography-derived fractional flow reserve to guide PCI. N Engl J Med. 2026;395(1):9-19. doi:10.1056/NEJMoa2600949
2. Daemen J, van der Eijk JA, Barbierato M, et al. Angiography-based physiology to guide coronary revascularization. N Engl J Med. 2026;395(1):20-31. doi:10.1056/NEJMoa2601841
3. Xu B, Tu S, Song L, et al. Angiographic quantitative flow ratio-guided coronary intervention (FAVOR III China): a multicentre, randomised, sham-controlled trial. Lancet. 2021;398(10317):2149-2159. doi:10.1016/S0140-6736(21)02248-0
4. Andersen BK, Sejr-Hansen M, Maillard L, et al. Quantitative flow ratio versus fractional flow reserve for coronary revascularisation guidance (FAVOR III Europe): a multicentre, randomised, non-inferiority trial. Lancet. 2024;404(10465):1835-1846. doi:10.1016/S0140-6736(24)02175-5
5. van der Valk VO, van der Loo WPM, Bruining N, et al. The current state of artificial intelligence-based invasive coronary angiography image analysis: a systematic review. Eur Heart J Digit Health. 2026;7(6):ztag110. Published 2026 Jul 13. doi:10.1093/ehjdh/ztag110