AbstractAimsWe compared diagnostic performance, costs, and association with major adverse cardiovascular events (MACE) of clinical coronary computed tomography angiography (CCTA) interpretation versus semiautomated approach that use artificial intelligence and machine learning for atherosclerosis imaging‐quantitative computed tomography (AI‐QCT) for patients being referred for nonemergent invasive coronary angiography (ICA).MethodsCCTA data from individuals enrolled into the randomized controlled Computed Tomographic Angiography for Selective Cardiac Catheterization trial for an American College of Cardiology (ACC)/American Heart Association (AHA) guideline indication for ICA were analyzed. Site interpretation of CCTAs were compared to those analyzed by a cloud‐based software (Cleerly, Inc.) that performs AI‐QCT for stenosis determination, coronary vascular measurements and quantification and characterization of atherosclerotic plaque. CCTA interpretation and AI‐QCT guided findings were related to MACE at 1‐year follow‐up.ResultsSeven hundred forty‐seven stable patients (60 ± 12.2 years, 49% women) were included. Using AI‐QCT, 9% of patients had no CAD compared with 34% for clinical CCTA interpretation. Application of AI‐QCT to identify obstructive coronary stenosis at the ≥50% and ≥70% threshold would have reduced ICA by 87% and 95%, respectively. Clinical outcomes for patients without AI‐QCT‐identified obstructive stenosis was excellent; for 78% of patients with maximum stenosis < 50%, no cardiovascular death or acute myocardial infarction occurred. When applying an AI‐QCT referral management approach to avoid ICA in patients with <50% or <70% stenosis, overall costs were reduced by 26% and 34%, respectively.ConclusionsIn stable patients referred for ACC/AHA guideline‐indicated nonemergent ICA, application of artificial intelligence and machine learning for AI‐QCT can significantly reduce ICA rates and costs with no change in 1‐year MACE.