MUNICH — Despite fewer lesions being treated, complete revascularization of nonculprit lesions with functional coronary angiography was associated with better outcomes than with conventional angiography in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, according to results from the AIR-STEMI trial.

Moving beyond visual estimation alone, “this approach brings complete revascularization closer to precision medicine by treating the lesions that matter while avoiding unnecessary percutaneous coronary intervention (PCI) in lesions that do not appear to limit blood flow,” reported Simone Biscaglia, MD, interventional cardiologist associated with the cardiology unit at the Azienda Hospital, University of Ferrara, Ferrara, Italy.

Based on 2023 guidelines from the European Society of Cardiology (ESC), complete revascularization is “the current gold standard” in multivessel STEMI, even if the relative value of physiology-guided conventional angiography has remained “unclear” after several studies, Biscaglia said. Clarifying the value was the “simple research question” of the international, randomized AIR-STEMI trial.

AIR-STEMI was presented by Biscaglia at the European Society of Cardiology (ESC) Congress 2026 and simultaneously published in The New England Journal of Medicine.

‘Practice-Changing’ Data

Colin Berry, MD, PhD, professor of cardiology and imaging at the University of Glasgow in Glasgow, Scotland, called the data “practice changing.” Berry, who was invited to discuss the trial at ESC, cited the highly significant 38% reduction in risk for a primary outcome event among those randomly assigned to functional angiography vs conventional angiography (hazard ratio [HR], 0.62; P < .001).

In this trial, 1823 patients with a STEMI and multivessel disease were randomly assigned to complete revascularization with physiology-guided angiography or conventional angiography within 48 hours of successful treatment of the culprit lesions with PCI. Patients with prior or planned coronary artery bypass grafting were excluded.

In both groups, clinically meaningful nonculprit lesions were defined by a diameter stenosis ≥ 50%. Lesion size was visually estimated, but candidate lesions in the functional group were further evaluated with fractional flow reserve (FFR), using an FFR value of 0.80 as the criterion for treatment.

The composite primary outcome was composed of death from any cause, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization.

Endpoints Favor Functional Angiography

Secondary endpoints, which included each individual component of the primary outcome, generally favored functional angiography numerically. 

The primary safety outcome — the first occurrence of contrast-induced acute kidney injury or major bleeding defined as Bleeding Academic Research Consortium type 3, 4, or 5 — was significantly less common in the functional vs conventional angiography group (4.6% vs 7.1%; HR, 0.63; 95% CI, 0.43-0.93; P = .02). When assessed individually, kidney injury (2.2% vs 4.0%) and major bleeding (2.5% vs 3.6%) were both numerically less common with functional vs conventional angiography. Biscaglia indicated that the 19.3% reduction in contrast use is likely to explain the lower rate of kidney injury.

The more targeted approach was also associated with fewer procedures. Although the number of lesions meeting the criteria for potentially meaningful were similar, 44.35% fewer nonculprit vessels were treated in the functional angiography group than in the conventional angiography group.

The advantage of physiology-guided angiography was consistent at least numerically across all subgroups evaluated, including those defined by sex, age younger vs older than 65 years, presence vs absence of diabetes, presence vs absence of renal impairment, involvement of three vessels vs fewer, and left ventricular ejection fraction < 45% vs > 45%, Biscaglia reported.

Tracing the journey to the AIR-STEMI trial, Berry cited the 2013 PRAMI trial, which established benefit from treating nonculprit lesions in multivessel STEMI, and the 2019 COMPLETE trial, which reinforced this benefit.

However, the value of functional angiography to perform complete revascularization was called into question by the 2021 FLOWER-MI trial, which found no additional benefit when wire-guided functional assessment was used.

As a result, the 2023 ESC guidelines gave a IA recommendation to complete revascularization, a IB recommendation to treat nonculprit lesions on the basis of angiographic severity, but a IIIC recommendation for employing functional assessments to guide treatment of nonculprit lesions.

In AIR-STEMI, only 1.3% of nonculprit vessels underwent a wire-based FFR assessment. Rather, this study provided robust support for functional angiography-based FFR, an outcome that Berry not only considers practice changing but also the likely basis for a guideline revision when the next set of ESC acute coronary syndrome recommendations is issued in 2027.

This investigator-initiated study received funding from Siemens Healthineers and SMT. Biscaglia reported financial relationships with both of these companies and with Abbott, Eikon, General Electric, Insight LifeTech, Medis, Pie Medical, and Pulse Medical. Berry reported financial relationships with Abbott Vascular, Acist, AskBio, AstraZeneca, Auxilius Pharma, Boehringer Ingelheim, CorFlow, Edwards Lifesciences, MAIA Pharmaceuticals, Merck, Servier, Novartis, and Vahaticor.

Ted Bosworth, a career medical writer based in New York City, has been covering advances in clinical medicine, including cardiology, for several decades.