Cor Vasa 2023, 65(1):69-75 | DOI: 10.33678/cor.2022.043

Inclisiran: new era of lipid-lowering therapy?

Jan Beneš

Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague

Dyslipidemia is the most frequent metabolic abnormality in western world population and a major risk factor for coronary artery disease (CAD) development. Dyslipidemia treatment is still insufficient and achieving target LDL-level infrequent. Statins are a cornerstone of dyslipidemia management. Although statins are one of the safest drugs on the market, statin therapy can be associated with muscle symptoms and increased risk of DM development. Statin discontinuation is frequent, often driven by negative media coverage. Inclisiran is a therapeutic oligonucleotide that employs RNA interference and inhibits the translation of PCSK9-mRNA leading to long-lasting LDL-cholesterol lowering. LDL-cholesterol-lowering effect of inclisiran is reversed at the rate of approximately 2% per month, so the effect of a single dose persists up to approximately two years. When administered once every six months, inclisiran therapy decreases the level circulating LDL-cholesterol by 50-55% and up to 65% in selected patient populations. Inclisiran therapy is not associated with alterations in platelet count, blood lymphocyte, monocyte or neu- trophil count, does not cause alterations in blood TNF-alpha or IL-6 concentrations and does not induce relevant anti-drug antibodies. The only relevant side effect is an adverse reaction at the injection site. In- clisiran thus has the potential to become widely prescribed drug that will greatly contribute to dyslipidemia management and further decrease of CAD incidence.

Keywords: Atherosclerosis, Coronary artery disease, Dyslipidemia, Inclisiran, LDL-cholesterol

Received: April 10, 2022; Revised: April 10, 2022; Accepted: April 24, 2022; Published: March 1, 2023  Show citation