Álvaro Rodrigo Alaíz

Background: Inclisiran is a novel lipid-lowering agent targeting PCSK9 via small interfering RNA (siRNA) technology. While clinical trials such as the ORION studies have demonstrated significant reductions in low-density lipoprotein cholesterol (c-LDL), real-world data (RWD) often differ due to variations in patient populations and clinical practices. Methods: This systematic review and meta-analysis adhered to PRISMA guidelines. A comprehensive search was conducted in MEDLINE for real-world studies evaluating inclisiran’s efficacy in reducing c-LDL. Articles meeting predefined inclusion criteria were assessed for quality and bias using RTI Item Bank. Data transformations were applied to harmonize median and IQR values to means and standard deviations for meta-analytic synthesis using RevMan 5.4. Results: A total of 3774 articles were identified, of which 7 studies comprising 1454 patients met the inclusion criteria. The meta-analysis revealed an average c-LDL reduction of 42.77% (95% CI: 37.42–48.12%). The subgroup analysis indicated greater reductions in patients receiving inclisiran alongside statins (45.67%; 95% CI: 36.64–54.71%) compared to monotherapy (37.53%; 95% CI: 29.91–45.15%). Discrepancies with clinical trials (e.g., 52% reduction in ORION studies) were attributed to baseline c-LDL differences and real-world adherence. Conclusions: Inclisiran demonstrates robust efficacy in real-world settings, achieving significant c-LDL reductions with a convenient dosing schedule. However, the observed discrepancies with clinical trials highlight the need for further RWD studies to bridge gaps in effectiveness and optimize therapeutic outcomes.