Serial OCT-based coronary physiology and plaque composition in vessels with nonobstructive coronary lesions following intensive lipid-lowering therapy: YELLOW III sub-study.

BACKGROUND AND AIMS: Non-obstructive coronary plaques are a major source of future coronary events, particularly when characterized by high lipid burden and adverse plaque morphology. While intensive lipid-lowering therapy promotes plaque regression, serial data linking quantitative plaque compositional changes to coronary physiology are limited. We aimed to evaluate the impact of maximal lipid-lowering therapy on coronary plaque composition and coronary physiology, using artificial intelligence (AI) based tissue characterization derived from OCT and optical flow ratio (OFR). METHODS: This was a serial intravascular imaging sub-study of YELLOW III. Stable coronary artery disease patients with lipid-rich, non-obstructive plaques (diameter stenosis of 30-50% on angiography) received Evolocumab in addition to high-intensity statin therapy. Paired baseline and 26-week follow-up OCT and NIRS-IVUS imaging were available for 105 coronary segments. AI-based OCT was used for quantitative plaque characterization, and OFR was computed as a surrogate of invasive fractional flow reserve. Changes in plaque composition and coronary physiology were assessed, and correlations between compositional changes and OFR improvement were evaluated. RESULTS: Amongst 105 paired coronary segments, total plaque volume decreased significantly over follow-up (201.2 ± 81.8 vs 191.3 ± 72.4 mm3; p < 0.001), driven primarily by reductions in lipid volume (p < 0.001) and macrophage volume (p = 0.006). Fibrous tissue volume showed a modest reduction, while its relative proportion increased, consistent with preferential lipid regression. Calcified plaque volume remained unchanged. Coronary physiology improved modestly, with an improvement in OFR (0.924 ± 0.062 to 0.932 ± 0.060; p < 0.001) and a reduction in lesion-level ΔOFR (p < 0.001). Improvement in OFR correlated inversely with reductions in total plaque volume (ρ = -0.286; p = 0.003), lipid volume (ρ = -0.257; p = 0.008), and lesion-level lipid burden assessed by LCBI (r = -0.23; p = 0.021). CONCLUSIONS: Maximal lipid-lowering therapy induces favorable quantitative changes in plaque composition and modest but significant improvements in coronary physiology in non-obstructive coronary lesions. AI-based OCT with OFR provides an integrated approach to link plaque biology with functional remodeling.