After 26 weeks of evolocumab, we observed a significant?and substantial shift toward more stable plaque phenotype on all three intracoronary image modalities including OCT, NIRS and IVUS in patients with stable CAD. The prevalence of vulnerable TCFA lesions in our study was high (48%) at baseline, and it was reduced to 13% after 26 weeks of evolocumab.?The beneficial changes in plaque morphology were associated with multiple activated transcriptomic pathways in peripheral monocytes leading to improved mitochondrial function and cell survival, oxidative stress alleviation, and suppression of immune cell adhesion and recruitment. The wide range of cholesterol-independent pleiotropic effects of evolocumab associated with plaque stabilization have been described for the first time in a clinical setting. While the majority of study subjects demonstrated significant changes in lesion morphology, leading to plaque stabilization, 20% of patients did not demonstrate an increase FCT, and 22% of subjects did not demonstrate reduced maxLCBI4mm after evolocumab therapy despite very low levels of LDL-C. Our machine learning transcriptomic models were able to predict individual patient’s response using baseline genes with high accuracy. Transcriptomic signature of beneficial response included multiple pathways modulating inflammation, matrix metalloproteinases, neutrophil degranulation and oxygen exchange.? #cardiology #interventionalcardiology #AHA2024 #yellowIII #mountsinaihospital
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