Role of Bailout Gene-Silencing Therapy in Plaque Lipid Reduction: Intravascular Imaging Study.

Introduction: Insufficient statin/ezetimibe effectiveness for low-density lipoprotein cholesterol (LDL-C) reduction is not uncommon. A novel gene-silencing medication inclisiran has been introduced. Near-infrared spectroscopy (NIRS) allows to assess the dynamics of plaque lipid content in the context of optimal lipid-lowering pharmacotherapy. The aim of this study was to evaluate the impact of optimal hypolipidaemic pharmacotherapy, including add-on inclisiran, on the plasma lipid profile and plaque lipid content.

Methods: This study enrolled patients with stable coronary artery disease, admitted for elective percutaneous coronary intervention (PCI). NIRS of the segment of interest was performed during index PCI and 15 months later. Patients having LDL-C >1.8 mmol/L after 4-6 weeks of maximum tolerated statin/ezetimibe therapy received add-on inclisiran. Lipid profile changes within 15 months were also evaluated.

Results: Among 42 included patients, 24 drug-resistant hypercholesterolaemia participants were assigned to inclisiran therapy. After 15 months, a significant LDL-C decrease of 26.42% was established (p = 0.006), with 12 participants reaching the LDL-C goal of <1.8 mmol/L. Average 15-month LDL-C reduction was 36.03%. NIRS data demonstrated a significant reduction in maximum lipid-core burden index within 4 mm (maxLCBI4 mm) in the inclisiran group (-117.64, p = 0.004) and statin/ezetimibe group (-141.88, p = 0.004), with no significant difference between the groups (p = 0.213).

Conclusion: Results demonstrate an association between better LDL-C control and coronary plaque lipid burden reduction. Addition of inclisiran leads to remarkable LDL-C reduction in patients who have run out of statin and ezetimibe treatment options.