Effect of inclisiran on lipid and mechanical vascular profiles in familial hypercholesterolemia subjects: results from a single lipid center real-world experience

Background and aims: Familial hypercholesterolemia (FH) is characterized by elevated LDL-C and an increased risk of premature cardiovascular events. Inclisiran is a small interfering RNA that inhibits hepatic PCSK9 synthesis and promotes LDL-C clearance by enhancing LDLR expression on hepatocytes. This study aimed to evaluate the efficacy of six-months add-on inclisiran on lipid profile and PWV in FH; furthermore, we investigated the association between LDL-C reduction and PWV variation. Methods: This prospective observational study involved 78 genetically confirmed FH subjects with an LDL-C off-target despite high-intensity statins plus ezetimibe. All subjects obtained biochemical analysis and PWV evaluation at baseline and after six months add-on inclisiran. Results: After six months add-on inclisiran, 41 % of subjects achieved LDL-C targets. Significant reductions of LDL-C (−41.5 %, p < 0.001), ApoB (−33.7 %, p < 0.01), Non-HDL-C (−35.9 %, p < 0.001), and Lp(a) (−18 %, p < 0.01) were observed, while PWV improved by 14.4 % (p < 0.001). In a secondary analysis, the Primary prevention group showed a higher prevalence of subjects on LDL-C target than the Secondary prevention group (59 % vs 23.1 %, p < 0.001). Both groups exhibited significant improvements of lipid profile and PWV (Δ - 14.1 %, p < 0.01 and Δ - 14.6 %, p < 0.001, respectively). Linear regression showed a significant association between ΔPWV and ΔLDL-C in the whole study population as well as in the Primary and Secondary prevention groups (p for all <0.001). Conclusion: Inclisiran significantly improved lipid profile and PWV in FH subjects. ΔPWV was significantly associated with ΔLDL-C.