FFR-Negative Nonculprit High-Risk Plaques and Clinical Outcomes in High-Risk Populations: An Individual _COMBINEPatient-Data _(OCT-FFR) Pooled _{and PECTUS-obs} Analysis From

BACKGROUND: Despite fractional flow reserve (FFR)–guided deferral of revascularization, recurrent events in patients with diabetes or after myocardial infarction remain common. This study aimed to assess the association between FFR-negative but high-risk nonculprit lesions and clinical outcomes. METHODS: This is a patient-level pooled analysis of the prospective natural-history COMBINE (OCT-FFR) study (Optical Coherence Tomography Morphologic and Fractional Flow Reserve Assessment in Diabetes Mellitus Patients) and PECTUS-obs study (Identification of Risk Factors for Acute Coronary Events by OCT After STEMI and NSTEMI Patients With Residual Non- Flow Limiting Lesions). Optical coherence tomography was performed on all FFR-negative (FFR >0.80) native nonculprit lesions. Patients or lesions with a high-risk plaque were compared with those without a high-risk plaque. A high-risk plaque was defined in the presence of at least 2 prespecified criteria: (1) lipid arc ≥90^o, (2) minimum fibrous cap thickness <65 µm, and (3) presence of either plaque rupture or thrombus. The primary end points were native major adverse cardiovascular events (composite of all-cause mortality, nonfatal myocardial infarction, or unplanned revascularization excluding stent-failure–related events and nonattributable events) and target lesion failure (composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization). RESULTS: Among 810 patients, 450 (55.6%) had a history of diabetes and 482 (59.5%) presented with myocardial infarction. At least 1 high-risk plaque was identified in 271 (33.5%) patients and 287 (30.6%) lesions. Over a median follow-up of 761 (interquartile range, 731–1175) days, the presence of a high-risk plaque was associated with patient-level native major adverse cardiovascular events (hazard ratio, 2.127 [95% CI, 1.451–3.120]; P<0.001) and lesion-level target lesion failure (hazard ratio, 2.623 [95% CI, 1.559–4.414]; P<0.001). The risk of adverse outcomes increased with the copresence of multiple high-risk features. CONCLUSIONS: FFR-negative but high-risk nonculprit lesions are associated with adverse patient- and lesion-level clinical outcomes. These findings emphasize the additional value of intracoronary imaging in patients with FFR-negative nonculprit lesions.