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Multicenter Study
. 2024 Jun 3;20(11):e707-e717.
doi: 10.4244/EIJ-D-23-00628.

Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial

David Del Val  1   2 , Balazs Berta  3   4 , Tomasz Roleder  5   6 , Krzysztof Malinowski  7 , Teresa Bastante  1   2 , Renicus S Hermanides  4 , Wojciech Wojakowski  5 , Enrico Fabris  8 , Javier Cuesta  1   2 , Giuseppe De Luca  9   10 , Fernando Rivero  1   2 , Fernando Alfonso  1   2 , Elvin Kedhi  5   11
Affiliations
Multicenter Study

Vulnerable plaque features and adverse events in patients with diabetes mellitus: a post hoc analysis of the COMBINE OCT-FFR trial

David Del Val et al. EuroIntervention. .

Abstract

Background: Thin-cap fibroatheroma (TCFA) lesions are associated with a high risk of future major adverse cardiovascular events. However, the impact of other optical coherence tomography-detected vulnerability features (OCT-VFs) and their interplay with TCFA in predicting adverse events remains unknown.

Aims: We aimed to evaluate the individual as well as the combined prognostic impact of OCT-VFs in predicting the incidence of the lesion-oriented composite endpoint (LOCE) in non-ischaemic lesions in patients with diabetes mellitus (DM).

Methods: COMBINE OCT-FFR (ClinicalTrials.gov: NCT02989740) was a prospective, double-blind, international, natural history study that included DM patients with ≥1 non-culprit lesions with a fractional flow reserve>0.80 undergoing systematic OCT assessment. OCT-VFs included the following: TCFA, reduced minimal lumen area (r-MLA), healed plaque (HP), and complicated plaque (CP). The primary endpoint, LOCE - a composite of cardiac mortality, target vessel myocardial infarction, or clinically driven target lesion revascularisation up to 5 years - was analysed according to the presence of these OCT-VFs, both individually and in combination.

Results: TCFA, r-MLA, HP and CP were identified in 98 (25.3%), 190 (49.0%), 87 (22.4%), and 116 (29.9%) patients, respectively. The primary endpoint rate increased progressively from 6.3% to 55.6% (hazard ratio 15.2, 95% confidence interval: 4.53-51.0; p<0.001) in patients without OCT-VFs as compared to patients with concomitant HP, r-MLA, CP, and TCFA. The coexistence of TCFA with other OCT-VFs resulted in an increased risk of the LOCE at 5 years.

Conclusions: In DM patients with non-ischaemic lesions, TCFA was the strongest predictor of future LOCE events. However, lesions that present additional OCT-VFs are associated with a higher risk of adverse events than OCT-detected TCFA alone. Further randomised studies are warranted to confirm these findings and their potential clinical implications.

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Conflict of interest statement

E. Kedhi reports personal lecture and advisory fees and institutional research grants from Abbott and Medtronic, outside the submitted work. W. Wojakowski reports personal fees from Abbott, outside the submitted work. R.S. Hermanides reports that he has received speaker fees from Abbott, Amgen, and Novartis. B. Berta reports that the Research Department of Cardiology of Isala has received an institutional research grant provided by Bayer outside the scope of the present study. The other authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1. Flowchart of the study population.
A) From a total of 550 diabetic patients, 388 with non-culprit, FFR-negative target lesions who underwent OCT assessment were included in the analysis. Among the 292 (75.3%) patients who presented lesions with at least 1 OCT-VF, 98, 190, 116 and 87 patients showed TCFA, r-MLA, HP, and CP, respectively; 96 (24.7%) patients had none of these VFs. B) Distribution and overlap of OCT-VFs in the entire cohort. CP: complicated plaque; FFR: fractional flow reserve; HP: healed plaque; OCT: optical coherence tomography; OCT-VFs: OCT-detected vulnerability features; r-MLA: reduced minimal lumen area; TCFA: thin-cap fibroatheroma
Figure 2
Figure 2. Main results.
A) Cumulative incidence of LOCE events in patients with lesions exhibiting different OCT-VFs compared to those without any OCT-VFs. B) Cumulative incidence rate of the primary endpoint (LOCE) with different combinations of OCT-VFs. C) The risk-scoring model for predicting 5-year LOCE-free survival based on the presence of OCT-VFs (r-MLA was considered a continuous variable. TCFA, CP and HP were considered dichotomous variables). CI: confidence interval; CP: complicated plaque; HP: healed plaque; HR: hazard ratio; LOCE: lesion-oriented composite endpoint; r-MLA: reduced MLA; OCT-VFs: optical coherence tomography-detected vulnerability features; TCFA: thin-cap fibroatheroma
Central illustration
Central illustration. OCT-defined vulnerability features and incidence of lesion-oriented composite endpoint.
A) Patients with diabetes mellitus presenting with intermediate, non-ischaemic (FFR >0.80) lesions underwent OCT assessment to identify OCT-based high-risk features for vulnerability. TCFA, r-MLA (<2.5 mm2), healed plaques, and complicated plaques were identified as OCT-VFs related to the lesion-oriented composite endpoint (LOCE). B) The cumulative incidence of the primary endpoint (LOCE) based on the combined presence of OCT-VFs. While the cumulative incidence of LOCE in patients who presented lesions without any OCT-VFs was notably low (6.3%), the progressive accumulation of OCT-VFs significantly increased the event rate (*none as reference). CI: confidence interval; CP: complicated plaque; DM: diabetes mellitus; FFR: fractional flow reserve; HP: healed plaque; HR: hazard ratio; r-MLA: reduced minimal lumen area; OCT: optical coherence tomography; OCT-VFs: OCT-detected vulnerability features; TCFA: thin-cap fibroatheroma
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