Inclisiran in ldl cholesterol reduction: systematic review of efficacy, safety, and clinical projection

Abstract

Dyslipidemia, particularly elevated low-density lipoprotein cholesterol (LDL-C), is one of the main modifiable risk factors for atherosclerotic cardiovascular disease. Inclisiran is a recently approved lipid-lowering agent that acts via small interfering RNA (siRNA), inhibiting hepatic synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9), thereby enabling a sustained reduction in LDL-C levels. The objective of this review was to analyze the efficacy, safety, and clinical projection of inclisiran as a therapeutic tool in patients with high cardiovascular risk. A systematic review was conducted using PubMed, applying the PRISMA 2020 methodology and restricting the search to studies published within the last five years. A total of 87 studies were retrieved, of which 10 were selected for qualitative synthesis. The included studies comprise randomized clinical trials, a systematic review with meta-analysis, one observational study, and complementary narrative reviews. The results show that inclisiran reduces LDL-C levels by approximately 50 % with a biannual dosing regimen, has a safety profile comparable to placebo, and promotes higher therapeutic adherence. Furthermore, achieving LDL-C targets through more intensive therapies is associated with a significant reduction in mortality in patients with ischemic heart disease. It is concluded that inclisiran represents an effective and safe alternative within the lipid-lowering therapeutic arsenal, especially in cases of statin intolerance or poor adherence, although further studies are needed to confirm its impact on major cardiovascular events and long-term cost-effectiveness.