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 OCT-detected vulnerability features (OCT-VFs) in the prediction of major adverse cardiovascular events (MACE) in non-ischemic 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 TCFA, r-MLA, h-PB, and 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, analyzed 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 to 30.25, p<0.001) in patients without OCT-VFs compared to 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. Conclusions: In patients with DM and non-ischemic 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.