FFR-Negative Nonculprit High-Risk Plaques and Clinical Outcomes in High-Risk Populations: An Individual Patient-Data Pooled Analysis From COMBINE (OCT-FFR) and PECTUS-obs
Authors: Volleberg Rick H.J.A. , Rroku Andi , Mol Jan-Quinten , Hermanides Renicus S. , van Leeuwen Maarten , Berta Balázs , Meuwissen Martijn , Alfonso Fernando , Wojakowski Wojciech , Belkacemi Anouar , Roleder Tomasz , Kedhi Elvin , van Royen Niels , Kedhi Elvin , Berta Balázs , Roleder Tomasz , Hermanides Renicus S. , Fabris Enrico , Ijsselmuiden Alexander J.J. , Kauer Floris , Alfonso Fernando , von Birgelen Clemens , Escaned Javier , Camaro Cyril , Kennedy Mark W. , Pereira Bruno , Magro Michael , Nef Holger , Reith Sebastian , Al Nooryani Arif , Rivero Fernando , Malinowski Krzysztof , De Luca Giuseppe , Garcia Garcia Hector , Granada Juan F. , Wojakowski Wojciech , Mol Jan-Quinten , Volleberg Rick H.J.A. , Belkacemi Anouar , Hermanides Renicus S. , Meuwissen Martijn , Protopopov Alexey V. , Laanmets Peep , Krestyaninov Oleg V. , Dennert R. , Oemrawsingh Rohit M. , van Kuijk Jan-Peter , Arkenbout Karin , van der Heijden Dirk J. , Rasoul Saman , Lipsic Erik , Rodwell Laura , Camaro Cyril , Damman Peter , Roleder Tomasz , Kedhi Elvin , van Leeuwen Maarten , van Geuns Robert-Jan M. , van Royen Niels 
Published: January 2025

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.

REGISTRATION:

URL:
https://clinicaltrials.gov
; Unique identifier: NCT02989740; Unique identifier: NCT03857971.