Association between high-intensity lipid-lowering therapy and atherosclerotic plaque content changes assed by iMAP-IVUS and near-infrared spectroscopy in patients with premature atherosclerosis

Abstract Background/Introduction The benefits of lipid-lowering drug treatment for the secondary prevention of coronary heart disease have been well-established by randomized, controlled trials. More evidence has now emerged to support the use of high-intensity low-density lipoprotein cholesterol (LDL-C) –lowering therapy including statine, ezetimibe, and PCSK9 inhibitors. Intravascular imaging, such as near-infrared spectroscopy (NIRS) can detect lipid-rich plaques. Virtual histology iMAP-Intravascular ultrasound (iMAP-IVUS) can classify tissue characteristics into 4 major components fibrotic, lipidic, necrotic, and calcified. Purpose Our study aimed to evaluate atherosclerotic plaque composition in very high cardiovascular-risk patients, who received high-intensity lipid-lowering therapy for 15 months. Methods Our study included stable coronary artery disease patients receiving statin and/or ezetimibe in maximum tolerated dose for at least one month, who were scheduled for PCI. In case LDL-C was >1.8 mmol/l, inclisiran was added to the therapy at the time of inclusion and continued for 15 months. The region of interest was a proximal or middle segment with angiographic evidence of nonobstructive de novo atherosclerosis >20% and <50%, evaluated by NIRS and iMAP-IVUS at baseline and 15 months later. After 15 months patients were classified into two groups – those who reached the European Society of Cardiology LDL-C target <1.8 mmol/L and those who did not. Statistical analysis was carried out with SPSS Statistics software, defining a significance level of 0.05. Results 37 eligible patients had undergone IVUS/NIRS investigation. The mean patient age was 53 years. After 15 months the mean LDL-C level decreased from 2.70 mmol/L to 1.79 mmol/l and 25 patients reached a target of <1.8 mmol/L. In the patient group that reached target - 4mm plaque lipid core burden index (LCBImax4mm) decreased from 184.00 (±160.07) to 62.72 (±142.19) with p=0.001 and total LCBI changed from 37.04 (± 40.80) to 15.60 (± 27.87) with p = 0.007. In patients with LDL-C >1.8 mmol/L, LCBImax4mm changed from 211.16 (±167.76) to 125.04 (±152.21) with no statistically significant difference p = 0.074. Similarly, the total LCBI was from 40.33 (± 43.38) to 22.41 (± 24.97) with p = 0.086. In iMAP-IVUS results necro-lipidic core in the <1.8 mmol/L group changed from 78.50 mm3 (±42.77) to 84.77 mm3 (±46.03) p = 0.422. Yet, second group's necro-lipidic core changed from 97.43 mm3 (±58.04) to 89.40 mm3 (±49.03), with no statistically significant difference p = 0.066. Additionally in both groups were significant changes in fibrotic tissues, for the target group from 139.50 mm3 (±69.86) to 147.32 mm3 (±73.56) p = 0.002 and from 149.71 mm3 (±82.79) to 160.09 mm3 (±89.01) p = 0.008 in second group. Conclusion Our study showed that after 15 months of high-intensity lipid-lowering therapy, patients that reached LDL-C levels <1.8 mmol/L, showed lower LCBImax4mm and total LCBI.