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

• Published in: Progress in cardiovascular diseases
• Main Authors: Bosco, Giosiana, Di Giacomo Barbagallo, Francesco, Di Marco, Maurizio, Scilletta, Sabrina, Miano, Nicoletta, Esposto, Stefano, Pennisi, Giovanni, Prezzavento, Simone, Gallo, Antonio, De Francesco, Ernestina Marianna, Malaguarnera, Roberta, Di Pino, Antonino, Purrello, Francesco, Piro, Salvatore, Scicali, Roberto
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 26.05.2025
• Subjects: Cardiovascular; Familial hypercholesterolemia; LDL cholesterol; Pulse wave velocity; Small interfering RNA; PCSK9i; FH; ASCVD; LDL-C; Small interfering RNA; ALT; mRNA; ESC/EAS; BP; Lp(a); HDL-C; ApoA1; SREBP2; Hs-CRP; PCSK9 mAB; ApoB; HbA1c; LDLR; BMI; AST; siRNA; PWV; TC; TG; Pulse wave velocity; Familial hypercholesterolemia; LDL cholesterol; FPG; LLTs; CPK; alanine aminotransferase; high-sensitivity C-reactive protein; total cholesterol; lipid-lowering therapies; high-density lipoprotein cholesterol; messenger ribonucleic acid; proprotein convertase subtilisin/kexin type 9 monoclonal antibody; blood pressure; creatine phosphokinase; body mass index; small interfering ribonucleic acid; fasting plasma glucose; apolipoprotein B; low-density lipoprotein receptor; low-density lipoprotein cholesterol; atherosclerotic cardiovascular disease; apolipoprotein A1; proprotein convertase subtilisin/kexin type 9 inhibitors; triglycerides; aspartate aminotransferase; glycated hemoglobin; sterol regulatory element-binding protein 2; European Society of Cardiology / European Atherosclerosis Society; lipoprotein(a)
• ISSN: 0033-0620; 1873-1740
• DOI: 10.1016/j.pcad.2025.05.008

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. 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. 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). Inclisiran significantly improved lipid profile and PWV in FH subjects. ΔPWV was significantly associated with ΔLDL-C. [Display omitted] •After six months add-on inclisiran, 41 % of FH subjects achieved LDL-C targets.•Significant improvements of lipid profile and PWV were observed after inclisiran treatment.•Primary prevention group showed a higher prevalence of subjects on LDL-C targets than the Secondary prevention group.•Both groups exhibited significant improvement of lipid profile and PWV.•ΔPWV was significantly associated with ΔLDL.