Noninferiority of angiography-derived fractional flow reserve (angio-FFR) was not met when compared to usual care in patients undergoing PCI, according to results of the PIONEER IV trial, presented at TCT 2026.

Patrick W. Serruys, MD, PhD, FACC, et al., randomized 2,130 patients undergoing PCI for a range of indications including chronic and acute coronary syndrome, NSTEMI, and STEMI to angio-FFR or usual care. The trial's primary outcome was a composite of all-cause mortality, stroke, myocardial infarction and revascularization at one year. The noninferiority margin was 3.2%. All patients received the HT Supreme drug-eluting stent and were prescribed dual antiplatelet therapy for one month post procedure followed by ticagrelor monotherapy for 11 months.

In the intention-to-treat analysis, the primary endpoint was observed in 7.4% of patients in the angio-FFR arm and 6.1% of the usual care arm (p=0.23) at one year. After adjustment for an interim analysis, the absolute risk difference was 3.44%, indicating that noninferiority was not met.

On the other hand, a prespecified per-protocol analysis found that angio-FFR was noninferior to usual care (5.5% vs. 5.3%, respectively; p=0.82; absolute risk difference after adjustment 2.35%).

In the angio-FFR arm (n=1,063), a total of 724 patients were adherent to pre- and postprocedural guidance. Among this subset of patients, 5.8% experienced the primary endpoint.

"The higher [patient oriented composite endpoint] rate was mainly driven by spontaneous NSTEMI in nontarget-vessel territories and was associated with the nonadherence to pre-PCI angio-FFR and device strategy," notes Serruys. "...PIONEER IV shows the importance of adherence to the suggested angio-FFR-guided PCI strategy."

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Vascular Medicine, Interventions and ACS, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Transcatheter Cardiovascular Therapeutics, TCT26, Acute Coronary Syndrome, Fractional Flow Reserve, Myocardial, Non-ST Elevated Myocardial Infarction, Percutaneous Coronary Intervention, ST Elevation Myocardial Infarction, Ticagrelor, Angiography, Stroke