Increased incidence of adverse events in diabetes mellitus patients with combined multiple vulnerable plaque features: new insights from the COMBINE OCT-FFR trial.

Aims: To evaluate the individual as well as combined impact of optical coherence tomography-detected vulnerability features (OCT-VFs) in the prediction of major adverse cardiovascular events (MACEs) in non-ischaemic lesions in patients with diabetes mellitus (DM).

Methods And Results: The COMBINE OCT-FFR (NCT02989740) was a prospective, double-blind, international, natural-history study that included patients with DM having ≥1 lesions with a fractional flow reserve > 0.80, undergoing systematic OCT assessment. Pre-specified OCT-VFs included thin-cap fibroatheroma (TCFA), reduced minimal lumen area (r-MLA), high plaque burden (h-PB), and complicated plaque (CP). The primary endpoint (MACE) was a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization, or hospitalization for unstable angina up to 5 years, analysed according to the presence of these OCT-VFs, both individually and in combination. TCFA, r-MLA, h-PB, and CP were identified in 98 (25.1%), 159 (40.8%), 56 (14.4%), and 116 (29.8%) patients, respectively. The primary endpoint rate increased progressively from 6.9% to 50.0% (HR = 10.10; 95% CI, 3.37-30.25, P < 0.001) in patients without OCT-VFs compared with those with concomitant h-PB, r-MLA, CP, and TCFA. Importantly, while TCFA, h-PB, r-MLA, and CP were individually associated with the primary endpoint, the presence of two or more OCT-VFs significantly increased the likelihood of adverse events at 5 years.

Conclusion: In patients with DM and non-ischaemic lesions, TCFA, h-PB, r-MLA, and CP were predictors of adverse events. However, the presence of two or more OCT-VFs significantly increased the likelihood of MACE at 5 years. Further studies are warranted to confirm these findings and their potential clinical implications in a randomized fashion.