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

Article · Bosco G, Di Giacomo Barbagallo F, Di Marco M, Scilletta S, Miano N, Esposto S, Pennisi G, Prezzavento S, Gallo A, De Francesco EM, Malaguarnera R, Di Pino A, Purrello F, Piro S, Scicali R

- Archive id: doi:10.1016/j.pcad.2025.05.008
- Published: 2025-05-26
- Venue: Progress in cardiovascular diseases
- DOI: https://doi.org/10.1016/j.pcad.2025.05.008
- PMID: 40436259
- Citations: 26
- Source URL: https://doi.org/10.1016/j.pcad.2025.05.008
- Provenance: europepmc

## Abstract

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.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Cardiovascular Therapeutics](https://space-kitty.com/topics/cardiovascular-innovation)

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