Coronary Physiology-Guided Revascularization in Chronic and Acute Coronary Syndromes: Medical Therapy, Placebo Procedures and Culprit-Only PCI as Distinct Comparators

Coronary physiological assessment refines lesion selection, but the randomized evidence addressing its clinical value differs according to the treatment comparison. This narrative review examines three distinct questions: (1) percutaneous coronary intervention (PCI) plus medical therapy versus medical therapy alone in selected chronic coronary settings; (2) PCI versus a placebo procedure for symptomatic stable angina; and (3) physiology-guided complete versus culprit-lesion-only PCI in acute coronary syndromes (ACS) with multivessel disease, with medical therapy provided in both arms. We reviewed pivotal randomized studies and follow-up publications through 31 October 2026 and considered contemporary trials comparing different physiological guidance methods separately. In chronic coronary settings, FAME 2 demonstrated a reduction in urgent revascularization, ORBITA-2 established a placebo-controlled angina benefit after withdrawal of background antianginal drugs, and NOTION-3 showed fewer myocardial infarctions and urgent revascularizations in patients undergoing transcatheter aortic-valve implantation, but included lesions eligible by either fractional flow reserve (FFR) or angiographic severity. In ACS, the results of trials comparing complete with culprit-only PCI vary; several composite benefits are driven by repeat revascularization, whereas FIRE also showed a reduction in cardiovascular death or myocardial infarction. These designs cannot isolate the benefit attributable to physiological selection from the benefit of treating additional lesions. Recent trials directly comparing angiography-derived physiology with alternative guidance strategies address a different question. FFR, non-hyperemic pressure indices, and angiography-derived measurements have distinct methodological and timing considerations, particularly after infarction. Overall, symptom relief, unplanned revascularization, and death or myocardial infarction should be interpreted separately; choice of revascularization strategy should integrate clinical presentation, anatomy, physiology, patient preferences, and optimized medical therapy.