ALL-RISE: A large-scale, global randomized trial of coronary physiology derived from conventional angiography compared with an invasive pressure wire-based approach to guide PCI
Reported from ACC.26
Mirvat Al Asnag provides her take on the ALL-RISE randomised trial presented by Ajay J. Kirtane at ACC.26 in New Orleans.
Background:
The current guidelines afford a class IA recommendation for the use of Fractional Flow Reserve (FFR), or any nonhyperemic pressure ratios (NHPR), to assess intermediate stenosis in patients with chronic coronary syndromes (CCS) before proceeding with percutaneous revascularization.(1-2) Yet there is an undeniable clinical inertia with respect to the utilization of wire-based physiology-based assessment of coronary arteries. Angiography-based physiology (FFRAngio) is an FDA-approved technology that is gaining traction. A 3-dimensional model is generated through “Resistance Flow” algorithm using artificial intelligence. It provides a multivessel physiological assessment of the entire coronary tree.(3)
Methodology:
The objective of the Angiography-Derived Fractional Flow Reserve to Guide PCI (All RISE) trial presented at ACC 2026 was to test whether FFRAngio is comparable to conventional pressure wire-based assessment of intermediate lesions being considered for percutaneous coronary intervention (PCI). 1,924 were enrolled in 60 sites globally. Patients were randomized to FFRAngio vs pressure wire guided PCI. They subsequently either underwent immediate PCI if the FFRAngio ≤ 0.80 or deferred PCI if the FFRAngio > 0.80. Similarly, immediate PCI was performed if the FFR ≤ 0.80 or NHPR ≤ 0.89 and deferred PCI if the FFR >0.80 or NHPR > 0.89. The primary endpoint was major adverse cardiovascular events (all-cause death, myocardial infarction (MI) or unplanned clinically-driven revascularisation) at 1 year.
The sample size and power calculations were based on the following premise:
- A non-inferiority margin set at 3.5% absolute risk difference
- An estimated MACE rate: 7.5% in both FFRangio and pressure-wire arms, with an attrition rate of 5%
- >80% power for the 1,924 randomised patients
Results:
Ultimately, a total of 1,930 patients were enrolled, with 969 in each arm. The mean age was 68 years, of whom 75.5% were men. Diabetics accounted for approximately 60% of the patients (11-13% were insulin-requiring). Just under 80% had hypertension or dyslipidemia, and 17% had a previous MI. Of note, 39% had previous PCI. Less than 10% were admitted with an NSTE acute coronary syndrome. Only 13% had an EF ≤ 50%.
The Left anterior descending artery accounted for ~50%, left circumflex artery ~20%, and right coronary artery ~30%. Intravascular imaging was employed in ~50% of the procedures in each arm.
| FFRAngio | Pressure wire | Differrence |
Total contrast volume (mL)
| 100.0 [52, 145 | 105.0 [72,150]
| -14.0* [-20.0,-10.0]
|
Total fluoroscopy time (min)
| 9.0 [5.0, 17.0] | 12.0 [8.0, 20.0]
| -3.0* [-3.0,-2.0]
|
Total Procedure time (min)
| 39.0 [21.0, 62.0] | 42.0 [29.0, 60.0]
| -5.0* [-7.0,-3.0]
|
FFRangio met non-inferiority to pressure wire-based assessment with the primary endpoint rate of occuring in 6.9% of the FFRAngio arm and 7.1% of the pressure wire arm (P 0.0008). The rate difference -0.2% and upper bound of 1-sided 97.5% CI 2.1% and a margin of 3.5%. In terms of the secondary clinical endpoints, the rate of death at 1 year was 2.3 and 2.1% respectively (HR 95% CI: 1.16 (0.62-2.14)) and MI was 1.6 and 2.5% respectively (HR 95% CI: 0.65 (0.34-1.25)). All subjects with follow-up in the 12-month visit window (days 335-395) were included in the analysis. Unplanned clinically driven revascularization occurred in 4.1 and 4.6% respectively (HR 95% CI: 0.90 (0.58-1.40)). The results appeared to be consistent across most of the prespecified subgroups with the possible exception of the subgroup with non-LAD and NHPR testing. Safety data were similar in the two groups.
Trial interpretation:
FFRAngio is a software-based tool that permits objective, rapid physiologic assessment of intermediate lesions. The trial was large and well-powered to assess treatment guided by FFRAngio compared with pressure wire, which has been the current standard of care. One-year MACE (6.9% vs. 7.1%) was similar, hence meeting non-inferiority. The shorter time to calculate FFRAngio may present a solution to the low uptake of physiologic evaluation and encourage complete revascularisation. FFRAngio allows a simplified tool without further manipulation with shorter procedure and fluoroscopic times as well as lower contrast volume. There is a slightly higher rate of PCI in the FFRAngio group. This may have been due to FFRAngio values near the threshold for revascularisation, for which immediate or deferred PCI have yielded similar outcomes in published trials.
It is noteworthy that the FAVOR III Europe trial was not noninferior to a pressure-wire–based FFR strategy.(4) There were worse clinical outcomes in both patients who underwent PCI. The different methodology of FFRAngio assessment may account for the discordant results. Interoperator variability during manual adjustments may be another explanation. A substudy in the FAVOR III Europe trial suggested a high degree of variability at the different participating sites and the core laboratory.(5)
Several limitations ought to be highlighted. The trial was unblinded and included coronary anatomy suitable for both pressure wire-based and FFRAngio based physiology measurements. This is consistent with most trials evaluating FFRAngio where it has been poorly validated in complex lesions.(6) The counterargument here would be that physiologic testing is required for intermediate lesions rather than the more complex high Syntax Score lesions. Patients who had undergone coronary artery bypass grafting were excluded, once again making these complex anatomies difficult to assess with FFRAngio. The majority of patients included in the trial had CCS with no biomarker elevation. As such, its role in assessing patients with an MI to guide complete revascularisation remains unknown. The results of the AIR-STEMI trial (Functional Coronary Angiography to Indicate and Guide Revascularization in STEMI Patients with Multi-vessel Disease) strategy in the assessment of nonculprit lesions in patients with NSTEACS and ST-segment elevation myocardial infarction are highly anticipated.(7)
Furthermore, its role in the presence of intracoronary imaging further complicates operators’ decision-making. Finally, FFRAngio was compared to a mixed control group of FFR/NHPR. Whether this contaminated the results and interpretation is difficult to know. Random differences in absolute event rates in the two groups cannot be determined through this trial as it was underpowered for that kind of analysis.
References:
- Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA guideline for the management of patients with chronic coronary disease: a report of the American Heart Association/American College of Cardiology Joint Committee on clinical practice guidelines. Circulation 2023; 148(9): e9-e119.
- Vrints C, Andreotti F, Koskinas KC, et al. 2024 ESC guidelines for the management of chronic coronary syndromes. EuHeart J 2024; 45: 3415-537.
- DOI: 10.1056/NEJMoa2600949
- Andersen BK, Holm NR, Mogensen LJH, et al. Coronary revascularisation deferral based on quantitative flow ratio or fractional flow reserve: a post hoc analysis of the FAVOR III Europe trial. EuroIntervention 2025; 21(3): e161-e170.
- Kristensen SK, Holm MB, Maillard L, et al. Repeatability and quality assessment of QFR in the FAVOR III Europe trial: the REPEAT-QFR study. EuroIntervention 2026; 22(1): e53-e65.
- Daemen J, van der Eijk JA, Barbierato M, et al. Angiography-based physiology to guide coronary revascularization. N Engl J Med. DOI: 10.1056/NEJMoa2601841.
- Erriquez A, Colaiori I, Hakeem A, et al. Functional coronary angiography to indicate and guide revascularization in STEMI patients with multivessel disease: rationale and design of the AIR-STEMI trial.Am Heart J 2025; 284: 71-80.
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