Key Points
- An angiography-derived FFR strategy (FFRangio) was noninferior to pressure-wire–guided assessment for the primary composite outcome of death, myocardial infarction, or unplanned revascularization at 1 year (6.9% vs. 7.1%; HR 0.98; 95% CI, 0.70–1.39; p<0.001 for noninferiority).
- Clinical outcomes, including death (2.3% vs. 2.1%; HR 1.16; 95% CI, 0.63–2.14) and myocardial infarction (1.6% vs. 2.5%; HR 0.65; 95% CI, 0.34–1.25), were similar between groups.
- FFRangio reduced procedural complexity, including shorter assessment time (6 vs. 8 minutes), lower fluoroscopy time (9 vs. 12 minutes), and less contrast use (100 vs. 105 mL), while maintaining comparable safety outcomes.
Physiologic lesion assessment using fractional flow reserve (FFR) is a cornerstone of contemporary coronary revascularization, with guideline recommendations supporting pressure-wire–based strategies to guide PCI. However, adoption remains limited due to workflow complexity and the need for invasive instrumentation. The ALL-RISE trial (NCT05893498), presented at ACC.26 and simultaneously published in the New England Journal of Medicine, evaluated whether an angiography-derived FFR strategy could simplify physiologic assessment while preserving clinical outcomes.
ALL-RISE was an international, multicenter, randomized noninferiority trial enrolling 1,930 patients undergoing coronary angiography with at least one intermediate (50–90%) coronary stenosis requiring physiologic assessment. Patients were randomized 1:1 to angiography-derived FFR (FFRangio; n=965) or pressure-wire–based assessment using FFR or non-hyperemic pressure ratios (n=965). The primary endpoint was a composite of death from any cause, myocardial infarction, or unplanned clinically indicated revascularization at 1 year.
At 1 year, the primary endpoint occurred in 64 patients (6.9%) in the FFRangio group and 65 patients (7.1%) in the pressure-wire group (HR 0.98; 95% CI, 0.70–1.39; absolute difference −0.2 percentage points; upper boundary of one-sided 97.5% CI, 2.1; p<0.001 for noninferiority), meeting the prespecified noninferiority margin. Individual components of the primary outcome were also similar, including all-cause mortality (2.3% vs. 2.1%; HR 1.16; 95% CI, 0.63–2.14), myocardial infarction (1.6% vs. 2.5%; HR 0.65; 95% CI, 0.34–1.25), and unplanned revascularization (4.1% vs. 4.6%; HR 0.90; 95% CI, 0.58–1.40).
Procedural efficiency favored the angiography-derived approach. The median physiologic assessment time was shorter with FFRangio (6 minutes [IQR, 4–10] vs. 8 minutes [IQR, 5–15]), with a between-group difference of −2 minutes (95% CI, −3 to −2). Total procedure time was also reduced (39 vs. 42 minutes; difference −5 minutes; 95% CI, −7 to −3), along with fluoroscopy time (9 vs. 12 minutes; difference −3 minutes; 95% CI, −3 to −2) and contrast volume (100 vs. 105 mL; difference −14 mL; 95% CI, −20 to −10).
Interestingly, a higher proportion of lesions underwent PCI in the FFRangio group (44.3% vs. 35.4%; odds ratio 1.45; 95% CI, 1.24–1.70), potentially reflecting differences in threshold interpretation near the ischemic cutoff. Despite this, downstream clinical outcomes remained comparable between strategies. Safety outcomes were similar between groups. Major bleeding (BARC type 3–5) occurred in 0.7% of patients in the FFRangio group and 1.5% in the pressure-wire group (HR 0.50; 95% CI, 0.20–1.23), and acute kidney injury was rare (0 vs. 0.1%). Procedural complications were infrequent and comparable overall. These findings suggest that angiography-derived physiologic assessment may provide a less invasive and more efficient alternative to pressure-wire–based strategies without compromising clinical outcomes. Dr. William F. Fearon, the study’s co–lead investigator, stated: “An angiography-derived FFR strategy has the potential to simplify physiological assessment in the catheterization laboratory while maintaining clinical outcomes comparable to pressure-wire–guided approaches.”