Purpose of Review Plasma levels of LDL cholesterol (LDL-C) are causally associated with cardiovascular risk. Reducing LDL-C results in a decreased incidence of cardiovascular events, proportionally to the absolute reduction in LDL-C. The inhibition of proprotein convertase subtilisin kexin 9 (PCSK) is a highly effective and safe approach to reducing LDL-C levels. In this review, we discuss the available data on the efficacy and safety of inclisiran, a siRNA targeting PCSK9 and propose a clinical profile for the patients who can benefit the most from this approach.Recent Findings Inclisiran is a small interfering RNA targeting the mRNA of PCSK9 specifically in the liver, owing to the conjugation with triantennary N-acetylgalactosamine. Randomized clinical trials have shown that inclisiran provides robust and durable reductions of PCSK9 and LDL-C levels, with a dosing schedule of once every 6 months after the initial and 3-month doses. These effects are consistent in different categories of patients, including patients with atherosclerotic cardiovascular disease and/or risk equivalent or patients with heterozygous familial hypercholesterolaemia. Ultimately the administration schedule may improve patients' compliance given also the favourable safety profile of the drug.Summary Completion of ongoing outcome clinical trials will provide information on both the expected clinical benefit and the safety of inclisiran administered for longer.

Inclisiran : How widely and when should we use it? / A. Pirillo, A.L. Catapano. - In: CURRENT ATHEROSCLEROSIS REPORTS. - ISSN 1523-3804. - 24:10(2022 Oct), pp. 803-811. [10.1007/s11883-022-01056-0]

Inclisiran : How widely and when should we use it?

A.L. Catapano
Ultimo
2022

Abstract

Purpose of Review Plasma levels of LDL cholesterol (LDL-C) are causally associated with cardiovascular risk. Reducing LDL-C results in a decreased incidence of cardiovascular events, proportionally to the absolute reduction in LDL-C. The inhibition of proprotein convertase subtilisin kexin 9 (PCSK) is a highly effective and safe approach to reducing LDL-C levels. In this review, we discuss the available data on the efficacy and safety of inclisiran, a siRNA targeting PCSK9 and propose a clinical profile for the patients who can benefit the most from this approach.Recent Findings Inclisiran is a small interfering RNA targeting the mRNA of PCSK9 specifically in the liver, owing to the conjugation with triantennary N-acetylgalactosamine. Randomized clinical trials have shown that inclisiran provides robust and durable reductions of PCSK9 and LDL-C levels, with a dosing schedule of once every 6 months after the initial and 3-month doses. These effects are consistent in different categories of patients, including patients with atherosclerotic cardiovascular disease and/or risk equivalent or patients with heterozygous familial hypercholesterolaemia. Ultimately the administration schedule may improve patients' compliance given also the favourable safety profile of the drug.Summary Completion of ongoing outcome clinical trials will provide information on both the expected clinical benefit and the safety of inclisiran administered for longer.
atherosclerotic cardiovascular disease; inclisiran; low-density lipoprotein cholesterol; primary prevention; secondary prevention
Settore BIO/14 - Farmacologia
   Low density lipoprotein receptor (LDLR)-independent effects of proprotein convertase subtilisin/kexin type 9 (PCSK9): role in modulating insulin-resistance, ectopic fat accumulation and low-grade inflammation
   MINISTERO DELL'ISTRUZIONE E DEL MERITO
   2017H5F943_001
ott-2022
Article (author)
File in questo prodotto:
File Dimensione Formato  
s11883-022-01056-0.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 986.25 kB
Formato Adobe PDF
986.25 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/952977
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 12
social impact