Intensified hypolipidaemic therapy with inclisiran for atherosclerotic plaque stabilization

High lipid content plaques in near-infrared spectroscopy (NIRS) are considered vulnerable. Recently PREVENT trial demonstrated benefits of percutaneous coronary intervention for unstable plaques.Aim of this study was to evaluate the capacity of intensive pharmacological low-density lipoprotein cholesterol (LDL-C) reduction including PCSK9 inhibition with inclisiran for plaque delipidation.This single-centre prospective pilot study enrolled 35 stable coronary artery disease patients with 20-50% stenosis in the proximal or middle third of a coronary artery. NIRS of the segment of interest was performed with 15-month follow-up, quantifying plaque lipid content by maximum lipid-core burden index within 4 mm (maxLCBI4 mm). Study participants were on high-dose statin (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and optional ezetimibe therapy for 4-6 week run-in period. In those not achieving LDL-C target <1.8 mmol/l add-on inclisiran was administered. LDL-C changes were also evaluated, baseline level referring to value at the time of optimal hypolipidaemic therapy initiation. For data analysis SPSS Statistics software was used, defining significance level alpha of 0.05.Before intensive statin treatment, mean LDL-C level was 2.7 mmol/l among all. In 16 patients mean LDL-C after the run-in period was 1.5 mmol/l. 19 patients not achieving LDL-C target with mean baseline LDL-C 2.4 mmol/l received inclisiran. After 15 months of inclisiran therapy, mean LDL-C level in these patients was 1.9 mmol/l, 9 patients achieving LDL-C <1.8 mmol/l. At 15-month follow up maxLCBI 4 mm reduction in statin/ezetimibe group from 211.3 to 92.0 by 56.5% (-119.3, P=0.016) and inclisiran group from 193.7 to 103.2 by 46.7% (-90.5, P=0.017) was established. Significant maxLCBI4 mm reduction by 62.4% (-112.4, P=0.005) was detected only in those being in LDL-C target <1.8 mmol/l, while for the others difference of 38.7% (-90.7, P=0.084) was not significant. Additionally, significantly lower fibrinogen level was detected in inclisiran group (P=0.017), indicating potential for residual risk reduction.Intensive pharmacological lipid lowering contributes to plaque stabilization evaluated by NIRS, LDL-C target achievement being important for lipid content reduction. Inclisiran is an effective bailout option for those not fully responsive to statin/ezetimibe.