Functional angiography outperforms conventional imaging in AIR-STEMI trial

Functional coronary angiography significantly reduced cardiovascular events and improved safety compared with conventional angiography in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. This was the main conclusion of the AIR-STEMI trial presented in a Hot Line session today at ESC Congress 2026 and published simultaneously in the New England Journal of Medicine.

Multivessel coronary artery disease – when at least two coronary arteries are blocked – affects almost half of patients who have STEMI, a common type of heart attack. ESC Guidelines recommend treating the blocked artery that caused the heart attack (the culprit lesion) plus other affected vessels (non-culprit lesions) using percutaneous coronary intervention (PCI), in order to achieve complete revascularization. Selecting which non-culprit lesions need to be treated with PCI is usually based on angiography.

Explaining the rationale for the AIR-STEMI trial, Associate Professor Simone Biscaglia from University Hospital of Ferrara, Italy, notes the limitations of current approaches: "Traditional coronary angiography provides a two-dimensional picture of narrowed vessels, which is subjective since it is interpreted by the human eye. Measuring the functional importance of additional blockages during the culprit procedure can be challenging." He describes how functional coronary angiography uses the angiographic images already acquired during the culprit procedure to reconstruct the coronary artery in three dimensions and to estimate blood flow, helping doctors identify which non-culprit lesions actually need treatment. "We designed AIR-STEMI to test whether this approach could improve outcomes in STEMI patients with multivessel disease," he said.

AIR-STEMI was an investigator-initiated trial conducted in 21 centers in Italy and Pakistan, which included patients with STEMI and multivessel disease who had undergone successful PCI for the culprit lesion. Patients were randomized to complete revascularization guided by functional coronary angiography or by conventional angiography. In the functional coronary angiography group, all qualifying non-culprit lesions were assessed using angiography-derived fractional flow reserve (FFR). Lesions with an FFR value more than 0.80 were deferred, whereas lesions with an FFR value less than or equal to 0.80 were treated with PCI. FFR analyses were centralized in the core lab. When PCI was indicated, the functional coronary angiography assessment was used to plan treatment by identifying the segment responsible for the greatest physiological impairment. In the angiography-guided group, PCI was recommended for all non-culprit lesions with stenosis of at least 50% estimated by conventional angiography. The study population included 1,823 patients who had a median age of 66 years and 24% were women.

In the functional coronary angiography group, 51.9% of non-culprit vessels underwent PCI compared with 94.9% of non-culprit vessels in the angiography-guided group. This translated into fewer procedures, fewer treated vessels, shorter treated segments and lower use of contrast agents with the physiology-guided strategy.

At a median follow-up of 17.9 months, the primary endpoint of all-cause death, MI, cerebrovascular accident or ischaemia-driven coronary revascularization was significantly reduced in the functional coronary angiography group compared with the angiography-guided group (8.9% vs.13.7%; hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.47 to 0.83; p<0.001).

Both procedure-related and spontaneous MI and also revascularization were significantly reduced with functional coronary angiography. There was no significant difference for all-cause mortality (3.9% vs. 5.1%; HR 0.77; 95% CI 0.50 to 1.20).

The main safety endpoint of contrast-associated acute kidney injury or major bleeding occurred less frequently in the functional coronary angiography group than the angiography-guided group (4.6% vs. 7.1%; HR 0.63; 95% CI 0.43 to 0.93; p=0.02).

Associate Professor Biscaglia concluded: "Functional coronary angiography allowed us to select and treat only those non-culprit lesions that were clinically important, reducing unnecessary procedures and the risk of complications. By moving beyond visual estimation alone, this approach brings complete revascularization closer to precision medicine: treating the lesions that matter, while avoiding unnecessary PCI in lesions that do not appear to limit blood flow. These results support functional coronary angiography as a new strategy to make complete revascularization more selective, safer and more personalized in this high-risk population."